Tissue Engineering and Regenerative Medicine

Stem cells alone or in combination with biomaterials have been investigated for their therapeutic potential in animal models of spinal cord injury (SCI), stroke and ALS. We compared human mesenchymal stem cells (MSCs) from bone marrow, a conditionally immortalized human stem cell line from fetal spinal cord (SPC-01) and human induced pluripotent stem cellderived neural precursors (iPS-NPs) for their capacity to migrate towards lesion sites, differentiate and induce regeneration.Transplanted cells were labeled with iron-oxide nanoparticles for MRI tracking. Animals were tested using motor and sensory tests. Animals with chronic SCI were implanted with HPMA-RGD hydrogels seeded with MSCs. In SCI, the best functional improvement was found after iPS-NP transplantation, followed by MSCs and SPC-01. MRI proved that the cells migrated into the lesion, survived for several months and differentiated into motoneurons and glia. Improved motor and sensory scores in chronic SCI were found after the implantation of biomaterials seeded with MSCs. Natural ECM hydrogels bridged the SCI lesion cavity, modulated the immune response and provided the substrate for in vivo neural tissue regeneration. Grafting of  iPS-NPs reversed stroke-induced somatosensory and motor deficits and protected the host substantia nigra from atrophy. MSC were also intrathecally applied to rat ALS-model (SOD1). Overall survival in the cell-treated group compared with the shamtreated group was prolonged, the cell-treated rats showed better motility, grip strength and greater numbers of perineuronal nets in the spinal cord. Our results demonstrate that the intrathecal application of MSCs can slow down progression of the disease.