Day 1 :
Keynote Forum
Giorgio Calori Maria
University of Milan
Italy
Keynote: From regeneration to substitution: Algorithm of treatment of non-unions and bone defects
Time : 09:05-09:30
Biography:
Giorgio Calori Maria has completed his education of Medicine and Surgery University of Milan in 1982; 1987 Specialization School in Orthopaedics and Traumatology University of Milan; 1990 Specialization School in Physical Therapy and Rehabilitation, University of Milan; 1994 Specialization School in Hand Surgery University of Florence. At present working as Chairman of Complex Operative Unit of Orthopaedic Reparative Surgery and Risk Management, G.Pini Orthopaedic Institute, piazza Cardinal Ferrari 1, University of Milan. Also as Professor at the University of Milan at the Graduate School of Orthopaedics and Traumatology and tutor of the course on “Biological processes in the repair of fractures and in nonunions “ since 2004. Professor at the University of Milan in the course in Medicine and Surgery of the course on “Human Anatomy “ since 2003 and of the course on “Orthopaedics and Traumatology “ since 2013. His relation with scientific sociteis as President of the European Society of Tissue Regeneration in Orthopaedics and Trauma (ESTROT.) President overseeing the super-specialist Society for osteosynthesis CIO (Italian Osteosynthesis Club) of the Italian Society of Orthopaedics and Traumatology (SIOT). President overseeing the Lombardy Section SLOTO of Italian Hospital Orthopaedics and Traumatologists. Former President of the Tissue Regeneration Commission of the Italian Society of Orthopaedics and Traumatology (SIOT). Member of the international Advisory Board on biotechnologies and regenerative medicine. President of the National Board for regenerative medicine.
Abstract:
Non-union and bone defects of long bones are difficult complications treating fractures. We propose a new classification and a new strategy that could give significant information to the orthopaedist for a good management of these complicated cases and permit to create comparable study groups for research purpose. In 2008 we published a new classification for nonunions: the Non-Union Scoring System (NUSS). The NUSS doesn’t consider only the radiographic aspects of the non-union but take in consideration all the risk factors that contribute to this complication analyzing the whole patient (bone quality, primary injury, number, invasiveness and adequacy of previous interventions, soft tissues status, ASA grade, clinical infection status, smoking status, use of drugs, blood test, diabetes). All the factors included in the scoring system have an impact on the complexity and difficulty of treatment of any nonunion. The NUSS recognizes four group of complexity:score from 0 to 25 should be considered a straightforward nonunion and should respond well to standard treatments; usually the problems is mainly biomechanic; the more common treatment is choosing a different system of fixation. score from 26 to 50 should require more specialised care; usually the problem is both biological and mechanical. The treatment require the correction of the fixation associated with a biological stimulation obtained with CEMP, ESWT or biotechnologies such as mesenchimal stromal cells or growth factors or scaffold in monorail therapy. score from 51 to 75 require specialised care and specialised treatments; it’s a complex problem characterized by a impairment of both biological and mechanic conditions, usually is required the resection of the nonunion and consequently a bone defect must be treated. Next to traditional treatments, such as bone transport with external fixator, autologous iliac‘s crest grafts or microvascular fibulas graft, in this situation is indicated the use of biotechnologies (cells, scaffold and growth factors) according to the principles of the “biological chamber” and the “polytherapy”. score from 76 to 100 may be candidates for the primary amputation, arthrodesis, prosthesis, o mega-prosthesis depending on the severity of the loss of substance and the anatomical localization. We think that a “ladder strategy” based on the complexity of patients that starts from reconstruction and ends with substitution of the affected limb could be a good option in these difficult cases in order to return these patients to function.
Keynote Forum
Denis Barritault
University Paris-EstCreteil
France
Keynote: Will matrix therapy pave the way to cell therapy and regenerative medicine?
Time : 09:30-09:55
Biography:
Denis Barritault graduated in Physics, completed his PhD in biochemistry in Paris University. Post doctoral in molecular immunology at Pasteur Institute and NYU as NIH Fogarty Fellow he joined INSERM unit in Paris as developmental biologist. He made the first description and patents of FGF extracted from retina in 1979 and 82 as skin and cornea healing agent, became full professor at Paris East university in 1985, founded and directed a CNRS Laboratory on cell and tissue regeneration until 2003. He is now President of OTR3, Emeritus professor and author in over 200 publications and 31 patents.
Abstract:
Matrix therapy is a newly coined name to emphasis the importance of the extracellular matrix in regenerative medicine. It is a complement to regeneration as cells are never alone but are part of an environment that makes a tissue or an organ. Heparan sulfates (HS) are key elements of the extracellular matrix (ECM), which store and protect various cell communication peptides (CCP). HS play a central role in tissue homeostasis, by modulating the bioavailability of CCP hence controlling the cell migration and differentiation required for healing processes. Tissue injury will lead to destruction of cells and surrounding ECM are destroyed. CCPs synthesized by inflammatory and circulating cells can then promote tissue repair, but with a loss of tissue quality, leaving scars or fibroses. We have engineered biodegradable nano-polymers mimicking the HS. They bind to the structure proteins of the damaged ECM, and to the CCP produced by healthy neighboring cells, thereby restoring the ECM microenvironment and tissue homeostasis. This matrix therapy approach has considerably improved the quality of healing in various animal models with reduction or absence of fibrosis resulting in a real regeneration process. These HS mimetics have therefore been named RGTA, for ReGeneraTing Agents. The RGTA technology has been validated in over 80 published preclinical studies and is now marketed as a human healing agent both for corneal and skin ulcers. RGTA are in development for more tissue injuries including mucosa, tendon, muscle. Altogether these study underline the potential of RGTAs as a new therapeutic class in the field of regenerative medicine, simple safe and exploiting our natural potential without need for exogenous cells supply but can combine with cell therapy to restore cellular microenvironment and favor homing . The future of regenerative medicine lays in a proper adjustment of the microenvironment to optimize cell colonization, expansion, replacement and recovery of the functions.
Keynote Forum
Babak Kateb
Chairman and President of Brain Mapping Foundation
USA
Keynote: Integration of nanotechnology, device, imaging, cellular stem cell therapeutics are key components of President Obama’s BRAIN initiative as well as SBMT G20 World Brain Mapping & Therapeutics initiative
Time : 09:55-10:20
Biography:
Babak Kateb, MD is a neuroscientist with more than 15 years of research experience. His research has been focused on introduction of advance diagnostics and therapeutics into clinical neuroscience in order to rapidly identify and introduce game changing technologies to treat neurological disorders such as brain cancer, Alzheimer’s disease, Parkinson’s disease, brain and spinal disorders. He did his Research fellowship at USC department of neurosurgery and also studied Neuroengineering at USC Ming Hsieh Institute.Babak established Society for Brain Mapping and Therapeutics (SBMT) while doing his fellowship 13 years ago at USC. Currently, he is the founding chairman of the board of directors & CEO Society for Brain Mapping and Therapeutics (SBMT), President and Scientific Director of the Brain Mapping Foundation and Director of National Center for Nano-Bio-Electronics.; the center is focused on integration of nanotechnology, cellular therapeutics/stem cell, medical device and imaging. He was Director of Research and Development at the Department of Neurosurgery at City of Hope Cancer Center. He is also Research Scientist at Department of Neurosurgery at Cedars Sinai Medical center. He is recipient of NASA Tech Brief Award for his pioneering work on sniffing cancer cells using NASA’s electronic nose. He has pioneered the technique for using NASA Multiwall carbon nanotubes to activate macrophages for brain cancer immunotherapy and recently has received an approval from the FDA to microwave soft tissue. The technology also could be used for brain, liver, head and neck, prostate and breast cancer. In 2015 Society for Brain Mapping and Therapeutics and Brain Mapping Foundation Board of Directors presented him with Pioneer in Medicine award. He has been recognized by Mayor of Los Angeles and Governor of California for his dedication in science. He is currently collaborating with Los Alamos National Lab and has duel appointment with NASA/JPL as a visiting scientist. His research at NASA and LANL involves the use of Artificial Intelligence and Supercomputing for Brain Mapping and therapeutics, use of electronic nose for cancer detection, application of new UV imaging for intraoperative brain mapping and use of LANL advance ultrasonic technology for brain stimulation; Babak has many patents in these areas. He has established a new publication with PLoSOne, which is called PLoSOne_ NeuroMapping & Therapeutics, which he serves as editor in chief and was the force behind 3 successful NeuroImage-Brain Mapping and Therapeutics special issues. He is editor of The inaugural Textbook of Nanoneuroscience and Nanoneurosurgery, published by, Taylor & Francis 2013 and the editor of the inaugural textbook of Neurophotonic and Brain Mapping, which is due for a release for Dec. 2015. He has been deeply involved in global neuroscience legislation through his close collaboration with the US Congressional Neuroscience Caucus as well as members of Canadian Parliaments. He has chaired 3 congressional briefing on Brain Mapping and given a talk to the Canadian Parliament. His initiatives have impacted the health care delivery to the wounded soldiers in the US. He has been one of the key players in President Obama’s BRAIN initiative and co-author of the G20 World Brain Mapping and Therapeutics Initiative and African Brain Mapping Initiative. He is also 13 times Marathon runner.
Abstract:
The field of Brain Mapping has been evolved rapidly in last few years. The field went from being defined by imaging to include, imaging, molecular/cellular and nano level mapping with detailed genetic and connectomic map. Today the Society for Brain Mapping & Therapeutics (SBMT) defines Brain Mapping as: The study of the anatomy and function of the brain and spinal cord through the use of imaging (including intra-operative, Microscopic, Endoscopic and Multi-Modality imaging), Immunohistochemistry, Molecular & optogenetics, Stem cell and Cellular Biology, Engineering (material, electrical and biomedical), Neurophysiology and Nanotechnology.In 2013 SBMT, Brain Mapping Foundation (BMF) along with few other organizations successfully helped the White House to formulate Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. The initiative is aimed at increasing our understanding of brain structure and function from imaging to nanoscale. BMF has been funding major partnership with NASA in order to integrate Nanotechnology, device, imaging and cellular, molecular and stem cell therapeutics. In this presentation, I will defining the nanoneuroscience, nanoneurosurgery and nanobioelectronics and their relationship with brain mapping while producing few examples.
- Track 1: Regeneration & Therapeutics
Location: Rome, Italy
Chair
Todd K. Rosengart
Baylor College of Medicine
USA
Co-Chair
Kristin Comella
Bioheart Inc.
USA
Session Introduction
Todd K. Rosengart
Baylor College of Medicine
USA
Title: Myocardial regeneration via cellular reprogramming
Biography:
Todd K. Rosengart is Professor and the DeBakey-Bard Chair of the Michael E. DeBakey Department of Surgery at the Baylor Medical College in Houston, TX. He received his MD degree through the Northwestern University Honors Program, obtained his general surgical training at New York University and served his cardiothoracic surgery fellowship at The New York Hospital. He was a Medical Staff Fellow in the Surgery Branch of the National Heart, Lung and Blood Institute. He holds twelve U.S. patents and is the author of over 150 peer-reviewed articles, editorials, reviews and book chapters. As a physician-entrepreneur, Dr. Rosengart is co-founder of Vitals.com and XyloCor Therapeutics.
Abstract:
Congestive heart failure (CHF), typically occurring as a result of myocardial infarction, is the leading cause of cardiac mortality in the West, afflicting over 5 million individuals and costing over $10 billion in medical care in the US alone. Cardiac stem cell therapy, which theoretically repopulates otherwise permanently scarred myocardium with contractile cells, has offered some promise in clinical trials. This strategy remains inherently constrained, however, by the hurdles of achieving adequate exogenous implant survival and integration into host myocardium. Potential risks of induced pluripotent stem (iPS) cell tumorigencity and immunogenicity may likewise limit these as stem cell implants. The recent discovery that “induced cardiomyocyte” (iCM) cells could be generated directly from somatic cells, for example using cocktails of transcription factors such as GATA4, MEF2c and TBX5, offers the remarkable new possibility of bypassing stem cell staging completely in the generation of autologous cardiomyocytes from cardiac fibroblasts. “Cellular reprogramming” likewise presents the intriguing possibility of converting scar fibroblasts in situ into functional iCMs, obviating entirely the challenges of exogenous cell implantation into a host myocardium. By converting scar directly back into functional myocardium, this transformational advance would eliminate the challenges of exogenous stem cell delivery that have slowed this field since its inception. While new evidence suggests that human cells may be more resistant to reprogramming than those transdifferentiated in small animal models, a number of methodologies are being developed to enable reprogramming even of human cells. Taken together, these new studies suggest an entirely new paradigm in CHF treatment that could potentially replace conventional therapies for end stage heart disease, include transplant and artificial heart implant strategies.
Kristin Comella
Bioheart Inc.
USA
Title: Adipose stem cells in vasculogenesis and angiogenesis
Time : 10:55-11:15
Biography:
Comella has over 15 years’ experience in corporate entities with expertise in regenerative medicine. She was recently named number 24 according to Terrapin’s list of the Top 50 Global Stem Cell Influencers. Ms. Comella has pioneered a variety of stem cell therapies including cord blood derived cells, bone marrow cells, muscle cells and adipose cells for use in many different applications. She has developed a wide range of regenerative products and techniques that have been successfully implemented into the clinic. She also led the team that gained the first ever FDA approval for clinical trials using a combined cell and gene therapy product. Ms. Comella has been a member of the Bioheart Inc. senior management team since 2004 and is currently serving as the Chief Scientific Officer and board member. Bioheart is a publically traded company focusing on the discovery, development and commercialization of autologous cell therapies for the treatment of degenerative diseases. Since joining Bioheart, she has played a major role in managing the product development, manufacturing and quality systems of cellular products. In addition, Ms. Comella is currently and actively serving on multiple boards in the stem cell arena. She was co-founder and Chief Executive Officer of Stemlogix, LLC for veterinary medicine. Ms. Comella has years of cell culturing experience including building and managing the stem cell laboratory at Tulane University's Center for Gene Therapy. Previously, she worked as a research engineer for Osiris Therapeutics developing stem cell therapies for osteoarthritis. Ms. Comella holds an M.S. in Chemical Engineering from The Ohio State University and a B.S. in Chemical Engineering from the University of South Florida.
Abstract:
The ready accessibility of adipose stem cells (ASC) make them a feasible and attractive form of autologous cell therapy requiring either no ex vivo expansion or relatively limited expansion. Our team has been working with ASCs for approximately 8 years. We have studied the effects of these cells in multiple indications in both animals and humans. ASCs are known to secrete angiogenic and anti-apoptotic factors which can increase tissue perfusion and limit ischemic tissue damage in several circumstances, including skeletal muscle, myocardial, and cerebral ischemia, as well as in cutaneous wound healing. ASCs may also be effective in orthopedic indications as they possess the potential to differentiate into bone and cartilage. This lecture will present the data that has been collected from thousands of patient treatments and discuss the potential of the cells in future applications.
Hyo Ihl Chang
Korea University
Republic of Korea
Title: Functions of natural pigments on gastric ulcer and cancer
Time : 11:15-11:35
Biography:
Hyo-Ihl Chang has completed his PhD in 1987 from North Carolina State University. He has been Professor of College of Life Sciences and Biotechnology, Korea University since 1988. He was a Dean of College of Life Sciences and Biotechnology, Korea University. Also he is a President of the Korean Society for Microbiology and Biotechnology in 2014. He has published more than 80 papers in reputed journals.
Abstract:
The Natural pigments have many applications in inflammatory, and oxidative related damage as well as in cancer chemotherapy. Recently, precise cellular roles of natural pigments, such as modulator of key cellular signaling pathway on variety diseases, are elucidated. On based on antioxidant, anthocyanins reduced naproxen-induced gastric ulcer. Anthocyanins reduced the level of lipid peroxidation and increased the level of the antioxidant enzymes. Anthocyanins increased the expression of Nuclear factor E2-related factor 2 (Nrf2) which is transactivator for cellular defense genes. Interestingly, anthocyanins induced gastrointestinal-glutathione peroxidase expression via Nrf2 that bind to regions of antioxidant response element (ARE) in GI-GPX promoter. Otherwise, Shikonin, and genipin stimulates production reactive oxygen species (ROS) in gastric cancer cells. They induced apoptotic cell death in gastric cancer cells in a caspase dependent manner. They also induced cell cycle arrest at G2/M phase via regulation of p21 by early growth response1 (Egr1). The p21 contains promoter region of Egr1 binding motif. Transient expression of Egr1 in AGS cells enhanced shikonin and genipin-induced p21 promoter activity, whereas suppression of Egr1 expression by small interfering RNA attenuated the ability of shikonin and genipin induced p21 promoter activity. Anthocyanins improve gastric ulceration through Nrf2 associated with antioxidant enzymes, such as GI-Gpx pathways. And, shikonin and genipin induced cell damage in AGS cells through the Egr1/p21 pathways.
Ana Maria Blanco Martinez
Federal University of Rio de Janeiro
Brasil
Title: Strategies to improve regeneration after peripheral nervous system trauma
Time : 11:35-11:55
Biography:
Ana Maria Blanco Martinez has completed her PhD at the age of 29 years from University of London, England, and postdoctoral studies from Rochester University, USA. She is an Associate Professor at the Federal University of Rio de Janeiro, Brasil, since 1985. She has published more than 100 papers in reputed journals and serving as an editorial board member of “Restorative Neurology and Neuroscience” and “International Journal of Neuropathology”. She has supervised 26 and 16 Master and PhD students, respectively, all in the field of Peripheral and Central Nervous System trauma.
Abstract:
Strategies aiming to enhance peripheral nervous tissue (PNS) regeneration after traumatic lesions are socially important because this condition is usually associated with permanent disabilities and low quality of life. Even in the PNS where axon regeneration is a well known process, only about 10% of adults who receive a surgical repair display full functional recovery. To evaluate strategies to improve regeneration, we have established models of trauma in the peripheral nervous system. In general, our projects are preclinical studies, in which we test a regenerative strategy. Our strategies include transection and tubulization with or without cell grafts and transection and tubulization with or without VEGF/GCSF gene therapy. Each one of these strategies is not capable of giving a significant result by itself, therefore there is a need for additional interventions that would have synergistic effects and maximize repair and functional outcomes. For that we use a combination of therapies, such as cell and gene therapy and rehabilitation procedures (treadmill training, for example). The results of our strategies are compared with autografts, the gold standard technique used by surgeons to repair a nerve lesion with tissue loss in humans. The tubulization technique mimics a lesion with tissue loss and is a manner to challenge the nerve to regenerate. The methods used to assess nerve regeneration and functional improvements include: Sciatic Functional Index, grasping test, eletroneuromiography, light and electron microscopy (transmission and scanning), immunohistochemistry, and enzyme activity of muscles. Our results clearly show that the strategies used are capable of enhancing peripheral nerve regeneration in terms of morphology and function.
Karin Schütze
CellTool GmbH
Germany
Title: Quality assurance for cell based therapeutics in 2D and 3D products
Time : 11:55-12:15
Biography:
Schuetze is a biologist and expert in non-contact cell handling and label-free cell analysis using innovative photonic technologies. She did her PhD work at the Institute for Applied Physical Chemistry in Heidelberg and her postdoc research at the University of California in Berkeley where she assembled her first Optical Trap. In 1993 she and her husband founded the PALM company, which was successfully sold to Zeiss. In 2008, they both founded their second company, the CellTool GmbH, where they develop Raman microscope systems for biomedical applications, providing physicians and biologists with a label-free and non-invasive tool for cell analysis.
Abstract:
In modern biomedicine there is an increasing demand for alternative, marker-free and non-destructive cell recognition and characterization methods. Raman Spectroscopy (RS) is a technology increasingly used for biomedical applications like identification of specific cell types. RS reveals detailed information on the metabolomic state of cells and tissues with the advantage that there is no need of labeling procedures. Here we demonstrate the feasibility of RS for quality control of 2D/3D cell based therapeutics exemplified for blood products and engineered human skin samples. In a first application RS was used to monitor erythrocytes and thrombocytes in donor blood over a time period of 30 and 8 days, respectively. Furthermore, Raman spectra were taken to identify and analyze fibroblasts, keratinocytes and melanocytes in a 3D human skin graft model. Raman Spectroscopy enabled quality control of blood products by allowing discrimination between young and old erythrocyte and thrombocyte samples. Thereby, differences found amongst the fresh and older samples were mainly associated with cells death. In 3D skin model it was possible to discriminate between different cell types and determine their allocation, also in a penetration depth up to 200µm, using RS. These two examples show that RS is a photonic marker for gentle yet highly specific detection and analysis of cells in biomedical products. It provides information about the entire metabolome of single cells even in a matrix setup with a depth of 200µm. Most importantly, RS can be used for quality assessment of cell cultures or engineered tissue without impairing cell viability.
Vicky Yamamoto
Keck School of Medicine of USC
USA
Title: Protein phosphatase/Smek complex negatively regulate Par3 and promote neuronal differentiation.
Time : 12:15-12:35
Biography:
Vicky Yamamoto is a cancer scientist at Keck School of Medicine of USC in the Department of Head and Neck Surgery with more than 10 years of research experience ranging from developmental neurobiology and stem cell to molecular targeted therapy. Prior to joining Keck School of Medicine of USC, Yamamoto worked at Mount St. Mary’s College, The Scripps Research Institute, the Cedars-Sinai Medical Center, and California Institute of Technology. Yamamoto received a PhD in biochemistry and molecular biology from Keck School of Medicine of USC. She has significant teaching experience and mentored numerous students.
Abstract:
Neural progenitor cells (NPCs) are self-renewing multipotent cells that are capable of differentiating into neurons and glial cells. Mechanisms that control the fate decisions of NPCs are not well understood. SMEK homolog 1, suppressor of mek1 (Smek-1) is a regulatory subunit of the serine/threonine protein phosphatase PP4. We found that Smek-1 is expressed in NPCs, promotes neuronal differentiation, and suppresses the proliferation of NPCs. Mass spectrometry analysis identified one of Smek-1’s binding partners, Par3. Par3, a cell polarity protein, is a negative regulator of neuronal differentiation. We demonstrate that Par3 is a substrate of Smek-1 and Smek-1 can negatively regulate its activity in neurogenesis. Interestingly, Smek-1 is expressed mainly in the nucleus but is exclusively localized in the cytoplasm during mitosis. We show that the cytoplasmic Smek-1 can interact with cytoplasmic Par3 and thereby mediate de-phosphorylation by the catalytic subunit PP4C. Collectively, our results show that the PP4/Smek-1 complex is likely a key regulator of neurogenesis.
Aysegul Batioglu-Karaaltin
Istanbul University Cerrahpasa School of Medicine
Turkey
Title: New approach for demaged fasial nerve regeneration based on stem cells
Time : 13:20-13:40
Biography:
Aysegul Batioglu-Karaaltin has completed her MD degree at the age of 24 years from Hacettepe University and her residency at the Department of ENT and Head and Neck at Ministry of Health Education and Research Hospital. She is working at Department of Otolaryngology Head and Neck Surgery, Istanbul University Cerrahpasa School of Medicine. She is carrying out more then 10 research about regenerative medicine and tissue engineering in the Head and Neck field. She has published more than 15 papers in reputed journals.
Abstract:
In facial nerve damage especially full-cut paralysis which can occur due to several conditions (congenital, tumor, iatrogenic-operation dependent), there is no spontaneous regeneration. Hence, several treatments are used to attempt regeneration of facial nerves such as end-to-end anastomosis, direct coaptation, artificial nerve guide conduit, autologous or decellularized grafts, anastomosis of distal facial nerve to the proximal cranial nerves. Since these techniques used have some disadvantages such as the limitation in source of Schwann cells, surgery intervention resulting in functional loss and difficulties in preparing nerve grafts, there is need for effective alternative techniques to be developed. Though the experiments associated with peripheral nerve injury in which adipose tissue, bone marrow, and hippocampal neural stem cell are used have obtained positive results, The usage of stem cells isolated from the olfactory region that is the only attainable neuronal stem cell in nerve regeneration if not the periferic nerve regeneration may provides an alternative treatment technique for facial nerve injury. Our group were used OSCs that isolated from olfactory mucosa tissue of human participants. 2mm excision was performed on right facial nerve for all rats. Reconstruction was performed with conduit in first group; conduit and phosphate-buffer saline in second group; conduit and labeled OSCs in third group. Rats were followed for whisker-movements and electroneuronography (ENoG) analyses. Recovery for third group were significantly different from first and second group. This study suggests that OSC may be used as a potent cellular therapy for accelerating regeneration of peripheral nerve injuries. A new study was designed for compared the effectiveness of adipose tissue, bone marrow and olfactory stem cells for facial nerve regeneration.
Ruiz-Navarro F
Austrian Society of Regenerative Medicine
Austria
Title: Neuron Point-Of-Care Stem cell therapy: Intrathecal transplant of autologous bone marrow-derived stem cells in patients with cerebral palsy. Preliminary Results
Time : 13:40-14:00
Biography:
Francisco Ruiz-Navarro (M.D) is Research Associate in the Austrian Society of Regenerative Medicine. Before, he was working as researcher at the Mexican Institute for Neurology and Neurosurgery in the Cerebrovascular Department focused in multi-centric population studies with Hispanic stroke patients. He was research assistant in the Center for Research and Advanced Studies of the National Polytechnic institute (CINVESTAV) in Mexico City at the Brain Bank and Physiology, Biology and Neuroscience Department. He was Research Assistant in La Raza Medical Center in Mexico City in the pediatric nephrology department. He obtained the Medical Degree in Anahuac University in Mexico City and became USMLE board certified in United States of America with outstanding grades. During his carrier he had been attending physician in different Mexican hospitals in Mexico City as part of general medicine, anesthesiology and neurosurgical teams. He performed clinical rotations at Jackson´s memorial Hospital
Abstract:
Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients with CP.
- Track 4: Tissue Regeneration
Track 5: Materials & Designs for Tissue Engineering
Chair
Shiva Akbarzadeh
Monash University
Australia
Co-Chair
Christopher L. Antos
Technische Universität Dresden
Germany
Session Introduction
Shiva Akbarzadeh
Monash University
Australia
Title: Use of clotted human plasma and aprotinin in skin tissue engineering - A novel approach to engineering composite skin on a porous scaffold
Time : 14:00-14:20
Biography:
Shiva Akbarzadeh obtained her PhD from the Ludwig Institute for Cancer Research, University of Melbourne in 2002. She has over 13 years of experience in cell biology and signalling in a variety of systems. In 2009 she established the Skin Culture Laboratory at the Victorian Adult Burns Service- the Alfred, focusing on translational research in skin regeneration. She leads the team responsible for manufacturing Cultured Epithelial Autograft for cellular based therapy of major burns and research in developing novel skin substitutes for clinical application. In addition, she provides lab based training on skin tissue engineering for scientists and surgeons from developing countries.
Abstract:
Tissue-engineered composite skin is a promising therapy for treatment of chronic and acute wounds, including burns. Providing the wound bed with a dermal scaffold populated by autologous dermal and epidermal cellular components can further entice host cell infiltration and vascularisation to achieve permanent wound closure in a single-stage. However, the high porosity and the lack of a supportive basement membrane in most commercially available dermal scaffolds hinders organized keratinocyte proliferation and stratification in vitro and may delay re-epithelization in vivo. The objective of this study was to develop a method to enable the in vitro production of a human skin equivalent (HSE) that included a porous scaffold and dermal and epidermal cells expanded ex vivo, with the potential to be used for definitive treatment of skin defects in a single procedure. A collagen- glycosaminoglycan dermal scaffold (Integra®) was populated with adult fibroblasts. A near normal skin architecture was achieved by addition of coagulated human plasma to the fibroblast-populated scaffold prior to seeding cultured keratinocytes. This resulted in reducing scaffold pore size and improving contact surfaces. Skin architecture and basement membrane formation was further improved by the addition of aprotinin (a serine protease inhibitor) to the culture media to inhibit premature clot digestion. Histological assessment of the novel HSE revealed expression of keratin 14 and keratin 10 similar to native skin, with a multi-layered neo-epidermis morphologically comparable to human skin. Furthermore, deposition of collagen IV and laminin-511 were detected by immunofluorescence, indicating the formation of a continuous basement membrane at the dermal-epidermal junction. The proposed method was efficient in producing an in vitro near native HSE using the chosen “off the shelf” porous scaffold (Integra®). The same principles and promising outcomes should be applicable to other biodegradable porous scaffolds, combined with autologous cells, for use in wound treatment.
Shuanhu Zhou
Brigham and Women Hospital Harvard Medical School
USA
Title: Adult stem cell aging and skeletal regenerative medicine
Time : 14:20-14:40
Biography:
Shuanhu Zhou, Ph.D. is an Associate Scientist at Brigham and Women's Hospital and Assistant Professor at Harvard Medical School. Dr. Zhou received his B.S. degree from Sichuan University, China and Ph.D. from Hebrew University of Jerusalem, Israel, and had his postdoctoral training in Harvard University, USA. Dr. Zhou has published more than 60 peer-reviewed papers and book chapters, and served as an evaluation expert for journals and organizations. He received several awards, including 2001 Rector Award of Hebrew University for excellent Ph.D. student and 2006 John Haddad Young Investigator Award from American Society for Bone and Mineral Research.
Abstract:
Regenerative potentials of many tissues are determined by the presence and functionality of adult stem and progenitor cells, which respond to exogenous cues to initiate tissue repair when needed. However, in many instances, resident adult stem/precursor cells suffer declining activity in response to aging, leading to reduced repair potential and chronic degenerative diseases. Human mesenchymal stem cells (MSCs) have been shown to be precursors of several different cellular lineages, including cartilage-forming chondrocytes and bone-forming osteoblasts. We reported that human marrow-derived MSCs show reproducible declines in proliferative and osteoblast potential with the age of the subject from whom the cells were obtained. Chemicals or drugs, which modulating endogenous MSCs, e.g. PTH and Vitamin D, have the potential to rejuvenate aged MSCs and to prevent or restore skeletal tissue degeneration and loss in the aging population. Tissue engineering approaches with adult stem cells have been applied clinically in cartilage and bone regeneration; however, more basic and translational researches as well as interactions between bench scientists and bedside clinicians are needed before tissue engineered biological organ replacement approaches with adult stem cells become standard clinical practice.
Lucie Bacakova
Institute of Physiology
Czech Republic
Title: Adhesion, growth and osteogenic differentiation of human adipose stem cells isolated by liposuction under low and high negative pressure
Time : 14:40-15:00
Biography:
Lucie Bacakova, MD, PhD, Assoc. Prof. has graduated from the Faculty of General Medicine, Charles University, Prague, Czechoslovakia in 1984. She has completed her Ph.D at the age of 32 years from the Czechoslovak Academy of Sciences, and became Associated Professor at the 2nd Medical Faculty, Charles University. She is the Head of the Department of Biomaterials and Tissue Engineering, Institute of Physiology, Academy of Sciences of the Czech Republic. She is a specialist for studies on cell-material interaction and vascular, bone and skin tissue engineering. She has published more than 150 papers in reputed journals (h-index 26).
Abstract:
Adipose-derived stem cells (ASCs) are promising for cell therapies and tissue engineering. Adipose tissue with these cells can be obtained by a relative non-invasive method, e.g. liposuction. The quality and quantity of ASCs can be influenced by the amount of negative pressure during liposuction. In this study, we focused on ASCs isolated from lipoaspirates taken from the same patient (a 43-year-old woman) under low negative pressure (-200 mmHg, LP) or high negative pressure (-700 mm Hg, HP). The ASCs were isolated by a method described by Estes et al. (Nat Protoc 5: 1294-311, 2010). Flow cytometry, performed in the 2nd passage, revealed that the cells contained markers typical for ASCs; only the population obtained under LP was more heterogeneous. The number of isolated ASCs and their subsequent proliferation activity in vitro was higher in cells obtained under HP. These differences persisted in passaged cells (tested up to 3 passages), after freezing and thawing of cells and also after seeding on Ti-Al-4V samples with various surface modifications (e.g., grinding, polishing, grit blasting, tarnishing), developed for construction of bone implants. However, when confluent ASCs were exposed to osteogenic medium (containing ascorbic acid, dihydroxyvitamin D3, dexamethasone, beta-glycerol phosphate and L-glutamine) for 5 days, the osteogenic cell differentiation, measured by intensity of fluorescence of collagen I, alkaline phosphatase and osteocalcin, was more pronounced in cells obtained under LP. Thus, ASCs obtained under both pressures have specific advantages, and their choice depends on their application, i.e. if their rapid growth or early differentiation is needed.
Christopher L. Antos
Technische Universität Dresden
Germany
Title: Calcineurin instructs when to stop regenerating once the correct size of zebrafish appendages is reached
Time : 15:00-15:20
Biography:
Christopher Antos, a Group Leader (Ph.D. Cell and Molecular Biology), who heads his laboratory at the DFG-Center for Regenerative Therapies Dresden, an Excellence Cluster at the Technische Universität Dresden. He got his Ph.D. at Southwestern Medical Center at Dallas, University of Texas (UTSW) and subsequently pursued a post-doctoral fellowship at the Max-Planck Institute for Developmental Biology in Tübingen, Germany, where he started researching regeneration biology using zebrafish as a model. Current research in Dr. Antos’s lab is focused on the molecular biology that regulates progenitor cell behavior during regeneration of zebrafish structures: principally, what is involved in inducing cells in the residual stump tissues to become progenitor cells and what is involved in instructing these progenitor cells to grow and pattern correctly. From this work, his lab uncovered that the previously uncharacterized molecule Smp is required for progenitor cell participation in regeneration and embryonic development is involved in the Wnt signal transduction by regulating β-catenin nuclear localization.
Abstract:
Animals that regenerate organs and appendages control the growth of stem and progenitor cells to reform lost structures to the same dimensions as the original structures. This proportional regeneration involves coordinating rapid allometric (disproportional) growth with the restoration of isometric (proportional) cell proliferation once the correct tissue dimensions are reached. It is unknown what executes this coordinated control. We show that the calcium-dependentphosphatase calcineurin regulates this control. Calcineurin inhibition results in continued allometric outgrowth of regenerating fins beyond their original dimensions. Congruent with these results, calcineurin activity is low when the rate of progenitor cell proliferation is highest, and its activity increases as the regeneration rate decreases. Furthermore, inhibition of calcineurin in uninjured adult fins switches isometric growth into allometric growth, demonstrating that calcineurin regulates appendage allometry. Previous results show that the rate of regenerative outgrowth is controlled by position along the proximodistal axis, but it is unknown what this positional control is. Our growth rate measurements and morphometric analysis of proximodistal asymmetry indicate that calcineurin inhibition shifts fin regeneration from a distal isometric growth program to an allometric proximal program. This shift is associated with the promotion of retinoic acid signaling, a signal transduction mechanism that affects positional information along the proximodistal axis. Furthermore, we provide evidence that calcineurin regulates potassium conductance via a potassium leak channel that has been shown to promote allometric growth. In summary, we identified a calcineurin-mediated mechanism that operates as a molecular switch between distal isometric growth and proximal allometric growth.
Urszula Stachewicz
AGH University of Science and Technology
Poland
Title: 3D imaging of cell interactions with nanofibers scaffolds
Time : 15:35-15:55
Biography:
Urszula Stachewicz is an assistant professor at AGH University of Science and Technology in Krakow, Poland, She is also working in the International Centre of Electron Microscopy for Materials Science. She received a doctorate from Delft University of Technology in the Netherlands and completed her postdoctoral study at the Queen Mary, University of London, UK. She worked in Philips Research Laboratories and the university spin-out company Nanoforce Technology Ltd. She is a peer reviewer for several funding agencies and journals and she is author of 20 peer reviewed publications.
Abstract:
The use of electrospun nanofibres for guided bone regeneration or bone scaffolds align with next-generation healthcare, especially as electrospun nanofibres are highlighted as being particularly effective in tissue engineering. However, optimization of the electrospinning process for cell growth and their interaction with nanofibre surfaces is yet to be determined. We develop a biodegradable electrospun nanofibre membrane for guided bone regeneration for bone scaffold applications. The interaction between osteoblasts and osteoblast-derived mineralized nodule formation on the nanofibre membrane is visualized using 3D imaging based on ‘slice-and-view’ combinations of ion beam and scanning electron microscopies (FIB-SEM). The presented 3D imaging technique therefore shows s a new approach in high resolution visualization the cell growth on electrospun nanofibers, and potentially other biomaterials, that will develop and design new biomaterials for a range of clinically important applications including orthopaedics of this work.
Paola Brun
University of Padova
Italy
Title: Hydrogel scaffolds in tissue engineering of the enteric nervous system.
Time : 15:55-16:15
Biography:
Paola Brun is an Assistant Professor at the Department of Molecular Medicine, University of Padova. She obtained her Ph.D. in 2005. Her scientific research activity covers a range of multidisciplinary topics mainly focused on cell biology, bioengineering and molecular medicine. She actively collaborates with the Departments of Industrial Engineering and Physics to find out innovative materials and techniques able to promote proliferation and differentiation of different cell populations. She has published 55 papers in peer-reviewed journals and she is an editorial board member of seven scientific journals.
Abstract:
The enteric nervous system (ENS) is the complex network of neurons and glial cells embedded within the gut wall that autonomously regulates most gastrointestinal functions. In the ENS, distinct neuronal subpopulations encode excitatory and inhibitory neurotransmitters. Indeed, interruptions in the neuronal network and derangement in the architecture of the myenteric ganglia have been linked to gastrointestinal dismotility and visceral sensory disorders. Since the extracellular matrix proteins have been long known to provide cues for migration and regeneration of neuronal cells, in this study we designed novel hydrogel scaffolds for intestinal tissue engineering. Peptides mimicking the extracellular matrix of the ENS were synthesized by Fmoc chemistry and differently conjugated. Enteric neurons were isolated from the longitudinal muscle myenteric plexus of young mice and seeded onto different decorated scaffolds. After 5 days on culture, cell adhesion, neuronal marker expression and neurochemical coding were evaluated by confocal microscopy and quantitative RT-PCR. Hydrogels containing laminin adhesive motif greatly promoted adhesion of neuronal cells relatively to other cells of the myenteric ganglia. Arg-Gly-Asp (RGD) motif supported the adhesion of glial cells and also induced expression of mRNA specific for neurotrophin-3, a soluble factor involved in neurogenesis. Ionic-complementary peptide EAbuK fostered axonal outgrowth. Finally, conjugation of RGD and laminin enhanced the expression of choline acetyltransferase, thus inducing cholinergic neurons. In conclusion, our study demonstrated that neuronal subpopulations are modulated by varying the composition of scaffolds. These observations will be helpful in the designed of engineered scaffolds personalized for the treatment of defects of the ENS.
Kara E. McCloskey
UC Merced
USA
Title: Vascularized cardiac tissue from induced pluripotent-derived cardiomyocytes and endothelial cells
Time : 16:15-16:35
Biography:
Kara E. McCloskey, PhD, is a Founding Associate Professor in the School of Engineering at the University of California, Merced. She received her BS and an MS in Chemical Engineering from The Ohio State University and her PhD through a joint program with Cleveland Clinic Foundation’s Biomedical Engineering Department and Ohio State University. She then completed her postdoctoral training in vascular stem cell and tissue engineering with Dr. Robert Nerem at the Georgia Institute of Technology. McCloskey is the founder and first chair of the Biological Engineering and Small-scale Technologies (BEST) graduate program at UC, Merced and serves as the university liaison for the UC Systemwide Bioengineering Multicampus Research Unit. Her research is in the field of cardiovascular tissue engineering with a specific focus on deriving functional cell products from stem cells. As a young investigator McCloskey earned a highly competitive $1.7 million New Faculty Award from the California Institute for Regenerative Medicine (CIRM) for studies towards developing cardiac tissue from stem cells, and another recent CIRM-funded Basic Biology award on directing specialized endothelial cell from stem cells. Dr. Kara McCloskey has over 14 years of experience in the area of endothelial cell (EC) fate from both human and mouse embryonic stem cells (ESC), and 9 years in cardiac fate, and now serves on the editorial board for the International Journal of Stem Cell Research & Therapy.
Abstract:
According to the American heart association, myocardial infarctions (MI) occur once every forty-four seconds in the United States. The chronic conditions that can develop from the damaged tissue requires the use of daily medications, pacemakers, and/or organ replacement in order to prevent congestive heart failure. Cardiovascular tissue engineering holds promising solutions to replace the need for whole heart transplants, and has made substantial progress towards repairing heart function after a MI. However, key challenges facing tissue engineering are 1) the source, 2) the packaging/delivery of cardiomyocytes (CM) in a manner that enables both cell survival and host integration, and vascularization of the new tissue. Our laboratory has developed a number of cell differentiation methods and engineering strategies addressing these key challenges in building functional heart tissue in vitro.
- Track 2: Stem Cells-Tools to Battle Cancer
Track 3: Bone and Cartilage Tissue Engineering
Location: Rome, Italy
Chair
Norman L. Lehman
The Ohio State University
USA
Co-Chair
Mei Wan
Johns Hopkins University School of Medicine
USA
Session Introduction
Ching-Chang Ko
University of North Carolina- Chapel Hill
USA
Title: Introducing a polydopamine-laced hydroxyapatite-gelatin nanocomposite for customized scaffolding in bone tissue engineering
Time : 16:35-16:55
Biography:
Ching-Chang Ko, is Professor of Orthodontics in the School of Dentistry at the University of North Carolina (UNC). He received his PhD in bioengineering and biomaterials from the University of Michigan. Since 2014, he has served as Program Director and Vice Chair of the Department of Orthodontics at UNC, and in 2014 was name Hale Distinguished Professor. He has contributed more than 100 publications to the scientific literature. His research is funded by NIH to develop new biomaterials for bone tissue engineering and to study orthodontic biomechanics. He is a member of AADR, AAO, ORS, ASME, ASCER, and Biomaterials.
Abstract:
Polydopamine has recently been reported to improve osteoblast adhesion and proliferation in vitro. We also found that preosteoblasts express functional dopamine receptors that could regulate cell proliferation and mineralization via the dopamine monomer released from the polydopamine-laced hydroxyapatite-gelatin nanocompsoite (PDHG). Thus, PDHG not only possesses enhanced physical properties of hydroxyapatite-gelatin bioceramics, but also can facilitate bone tissue engineering. The interconnection of polydopamine network within PDHG increases both compressive and tensile strength, approaching to that of natural cortical bone. The present study determined dose ranges for dopaminergic effect in osteogenesis, which will be used to optimize the composition of PDHG. In vitro tests of MC3T3-E1 culture used soluble dopamine drops and the real-time polymerase chain reaction (qPCR). At the end of culture, the expression of osteogenic genes was quantified with and without addition of dopamine antagonists. In a pilot in vivo test, a thermodifferential process in conjunction with the indirect scaffolding technique was applied to fabricate a customize PDHG prosthesis for jaw bone regeneration in rats. The 3mm resection of rat mandible was created at the premolar and molar region. The PDHG porous prosthesis was used to fix the osteomized mandible. The result showed that osteogenic gene expression was significantly greater in the dopamine-treated than control group (p<0.05), but inhibited by dopamine receptor antagonists. The rats underwent PDHG reconstruction behaver normal chewing and life activities; histological retrieval is currently underway.
Norman L. Lehman
The Ohio State University
USA
Title: Glioma tumor stem cell based models for evaluation of anti-glioma therapeutics.
Time : 16:55-17:15
Biography:
Lehman has completed his MD and PhD from the University of Southern California and postdoctoral studies from Stanford University School of Medicine. He is currently the Director of Neuropathology at the Ohio State University. He has published more than 50 per reviewed papers and has served as an editorial board member for Acta Neuropathologica and is an Associate Editor for the Journal of Neuropathology and Experimental Neurology.
Abstract:
Experimental models for anti-glioma therapies are limited by two important factors. Appropriate modeling of the blood-brain tumor barrier and modeling of the tumor stem cell component. The latter is important because glioblastoma tumor stem cells are more resistant to chemotherapy and radiation compared to the general population of glioma tumor cells. These problems have been approached using orthotopic xenograft models in rodents. Similar to fetal neural precursors, glioma stem cells can be cultured from tumor samples in the form of neurospheres. Human glioblastoma tumor stem cell neurospheres can be stereotactically injected into rodent brains, e. g., nude mice, which allows for tumor formation. The animals can then be treated with drugs or other anti-glioma modalities allowing close modeling of the blood-brain tumor barrier. Such models have successfully been used to test the efficacy of several experimental therapeutics, including Aurora-A kinase inhibitors in our laboratory. The benefits and limitations of using glioblastoma tumor stem cells compared to conventional tumor models will be discussed.
Brian Mehling
Blue Horizon International
USA
Title: Safety study of intravenously administered human cord blood stem cells in the treatment of symptoms related to chronic inflammation
Time : 17:35-17:55
Biography:
Brian Mehling is a practicing American orthopedic trauma surgeon, researcher, and philanthropist. He is spearheading groundbreaking research in stem cell therapy through his company, Blue Horizon International, a healthcare consulting organization focused on treatment and research using stem cells. He started his path in medicine through undergraduate study at Harvard University, obtaining his Bachelor of Arts and Master of Science degrees in Biochemistry from Ohio State University. Completing his degree of medicine at Wright State University School of Medicine, he received post graduate education through residencies and fellowships at St. Joseph’s Hospital in Paterson, NJ and the Graduate Hospital in Philadelphia, PA, while pursuing a Ph.D. in Chemistry.An orthopedic trauma surgeon, Mehling operates his own practice, Mehling Orthopedics, in both West Islip, NY and Hackensack, NJ. He is also on call at Good Samaritan Hospital, Hackensack University Medical Center, Hackensack University Medical Center at Pascack Valley, St. Joseph’s Medical Center, and St. Joseph’s Wayne Medical Center. Mehling has traveled extensively throughout Asia and the Middle East observing firsthand the differences in healthcare standards. Identifying the need for a universal high quality standard, he founded Blue Horizon International. He and his colleagues have successfully treated and monitored more than 600 patients using stem cell and regenerative therapies. Patients have been treated for a wide range of diseases and disorders including spinal cord injury and cerebral palsy. Mehling founded the Blue Horizon Charitable Foundation to enhance the quality of health to those in need. Efforts are focused on helping human service and health organizations, while also providing resources benefitting children orphaned from war and disease. Apart from his organizations, Dr. Mehling personally contributes his time and resources to charitable causes. He has sponsored patients’ trips to China for stem cell treatments, as well as hosting charitable events from his own homes in New York, the Hamptons, and France. Notable beneficiaries include The Sean Kimmerling Testicular Cancer Foundation and the Children of Chernobyl.
Abstract:
Stem cell research plays an important role in orthopedic regenerative medicine today. Arthritis literally means "inflammation of a joint." Mesenchymal Stem Cells (MSCs) represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. The purpose of this study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.
Luguang Luo
Roger Williams Hospital, Charter Care-Prospect RI LLC
USA
Title: The advantage of bioengineering and stem cell approach for immunorejection free human islet
Biography:
Luguang Luo has been trained by medical physician and molecular biology background (Umass Medical Center and Brown Medical School USA) for more than 30 years. He initiated his career with senior outstanding endocrinologist Dr. Ivor Jackson at Brown Medical School. Dr. Luo’s significant contribution is to identify Thyrotropine Releasing Hormone (TRH) expression in pancreatic β-cell and may contribute β-cell regeneration. Since he became independent investigator, he collaborates with Dr. Quesenberry, experts in hematology, his efforts have been focusing bone marrow stem cells and diabetes and published more than 50 articles in peer reviewed Journals and about 100 abstracts presentations in American Diabetes Association Annual Meeting and Endocrine Association Annual meeting and others which lead him to receive numerous funds from JDRF, NIH and local hospitals. Recently, Dr. Luo focuses on to establish a microenvironment in retaining a balance of β-cell apoptosis and regeneration, resulting in the support of pancreatic β-cell survival and function while developing bioengineering approach to create immunorejection free human islet tissue. Dr. Luo is a Director of stem cell and diabetes Research Center in Roger William Hospital and professor affiliated with BU and Brown Medical schools. Dr. Luo is a reviewer in NIH study section and cNSF and has also been invited to review articles for numerous Journals such as Molecular Endocrinology, Journal of Neurology, Endocrinology, et al and Editor Board members.
Abstract:
Islets transplantation holds promise as a long term treatment to Type I diabetes. We have previously reported that bone marrow cells (BM) co-cultured with human islets generate a microenvironment suitable for repairing islets and promoting longevity. Our work strongly supports that BM and its subpopulation creates a microenvironment which sustains human islet beta cell function and survival in long-term. In additional, we found that the role from BM derived populations is of diversity. We hypothesize that mechanism of BM support human islet includes repair human islet injury, initiating human isle regeneration through vascularization and initiating beta cell transcription factor activations. Coculture human allogeneic BM and islet generates a reinstituted human islet tissue which suitable for transplantation in vivo for diabetes therapy. However, in vivo immunorejection issue still yet overcome with this reinstituted tissue. We hypothesize that co-encapsulated BM will generate microenvironment for human islet longevity while preventing immunorejection. This work provides exciting results for supporting the hypothesis. APA encapsulation was established by coating gel beads with additional layers of poly-L-ornithine and alginate to create a 4-layered immunoisolatory membrane. Optimal condition was created and tested. After 4 weeks of culture, encapsulated human islets with BM formed a 3D structure while groups without encapsulation formed a 2D structure. The advantage of this new approach also approved in vivo by transplantation encapsulated human islets in immunologically competent STZ-induced diabetic rats. Our results show that encapsulated human islets with BM creates a microenvironment benefitting human islet function/longevity while preventing immunorejection. We will summarize the advantage from our and others to propose potential clinical application of this novel discovery.
Mei Wan
Johns Hopkins University School of Medicine
USA
Title: Mobilization and differentiation of multipotent nestin+ stem cells during arterial remodeling
Biography:
Mei Wan is an Associate professor of the Center for Musculoskeletal Research, Department of Orthopaedic Surgery at Johns Hopkins University School of Medicine. She obtained her Ph.D. in Pathophysiology at Hebei Medical University in 1997. Her research for the past 17 years focuses on characterizing the mechanisms by which bone marrow mesenchymal stem cells (MSCs) are regulated in various physiological and pathological conditions such as bone remodeling, cancer development, vascular disorders, and tissue repair/remodeling. At earlier years of her career, she demonstrated that the role of proteosome degradation pathway in the regulation of TGFβ signaling. She also identified the central mechanism through which parathyroid hormone stimulates bone formation, which had been the major unresolved question in bone field. In recent years, she found that active TGFβ can be released from tissue in response to perturbations to the local environment such as bone remodeling (Nat. Med. 2009, Cell Stem Cell 2011), arterial injury (Stem Cells 2012, Stem Cell Dev. 2014), and lung injury (J. Immunol. 2014). The released active TGFβ stimulates the migration of MSCs to participate in tissue repair or remodeling. Currently, Dr. Mei Wan is an editorial board member for Journal of Bone and Mineral Research and Bone Research.
Abstract:
Multipotent mesenchymal stem cells (MSCs) can mobilize into the circulating blood under many circumstances, such as serious disease, injury, or stress. MSCs then migrate to the remodeling sites and differentiate toward distinct lineages of cells. However, the primary factors and signaling pathways that control MSCs recruitment to the injured sites and their commitment/differentiation into lineage-specific local cells are largely unknown. Here we show that active TGFβ controls the mobilization of MSCs to circulating blood in response to arterial injury and their recruitment to the target sites, where the cells give rise to either endothelial cells to repair the damaged endothelium or smooth muscle cells (SMCs)/myofibroblasts contributing to intimal hyperplasia. In our animal models of arterial injury, about 50% of the neointimal cells were derived from MSC lineages. Using an ex vivo cell migration assay established in our laboratory, we found that TGFβ activated from the injured vessels induces MSC migration, and this effect is mediated by Smad-MCP1 signaling cascade. Moreover, active TGFβ produced from the injured vessels also activated RhoA-ROCK signaling in MSCs and induced their differentiation to SMC/myofibroblastic neointimal cells. Inactivation of ROCK maintains the stemness of MSCs and their differentiation capacity to endothelial cells. Importantly, treatment of the arterial injured mice with ROCK inhibitor promoted re-endothelialization and inhibited neointima formation of the vessels. Thus, pharmacotherapies that inhibit RhoA-ROCK signaling offer a new therapeutic target for treating cardiovascular disease by promoting endothelium repair and inhibiting pathological intimal hyperplasia.
Somaieh Kazemnejad
Avicenna Research Institute
Iran
Title: Menstrual blood derived stem cells as a renewable source of adult stem cells: Features and advantages
Biography:
Somaieh Kazemnejad is associate professor and director of Tissue Engineering department in Avicenna Research Institute, where she leads the Regenerative Medicine Group, a multidisciplinary team of researchers including engineers, cell biologists, polymer chemists, clinicians, and veterinary surgeons. She was born in 1979 and completed her Ph.D at the age of 27 years from Tarbiat Modarres University of Iran. She is a Clinical Biochemist who is one of very few Iranian academics in the field of regenerative medicine and tissue engineering to have taken a research programme from fundamental research through to clinical application utilizing research in-vitro, in-vivo, preclinical large animal studies and clinical trials with focus on menstrual blood stem cells. She has published more than 28 papers in reputed journals in the field of tissue engineering and regenerative medicine.
Abstract:
Menstrual blood derived stem cells (MenSCs) can be easily obtained from women’s menstrual blood in a non-invasive technique without ethical issues of other stem cell types. These multipotent cells have the ability to differentiate into various functional cells, including osteocytes, adipocytes, cardiomyocytes, respiratory epithelial cells, neurocytes, myocytes, endothelial cells, pancreatic cells and hepatocytes. No evidence of tumor and ectopic formation, or any immune response has been demonstrated after being transplanted into animal models. To determine whether MenSCs outline common features with bone marrow-derived stem cells (BMSCs) or have source-specific peculiarities, we have done a head-to-head comparison of MenSCs with BMSCs in aspect of immunophenotyping, proliferation and differentiation characteristics. The evidence presented here narrates MenSCs are unique stem cell population with higher rate of proliferation and different trans-differentiation potential compared to BMSCs. Probably, it can be attributed to the particular immunophenotypic pattern and special signaling molecules involving in MenSCs development. In addition, we reviewed the possibilities of using MenSCs for diagnosis of diseases and as a novel alternative to current cell sources for cell-based therapies of neurological disorders, myocardial infarction, type I diabetes mellitus, liver cirrhosis, etc. Therefore, this study presents broad insights about possible advantages of MenSCs and their safety/efficacy profile for clinical applications. Key words: Menstrual blood-derived stem cells (MenSCs), Regenerative medicine, cell therapy