Tissue Science and Regenerative Medicine

In 2004 we started a project on revascularization of legs with critical ischemia (CLI). Eleven years later a similar approach was employed to improve vascularization of the femur with avascular necrosis (AVN). In both attempts a leukophoretic product resulting from the separation (Spectra, Optia) of 500 mL of the marrow was injected in small portions into the calf of legs with ischemia or into Kirschner wire drilled holes penetrating the head of the femur.  In CLI patients employed procedure resulted in a prompt relief of pain followed by healing of the ulceration and significantly prolonged intervals between episodes of intermittent claudication. Forty six percent of patients benefited from the improvement. As to AVN, an improvement seen in 3 out of 5 patients was reported as pain relief and improvement in movement. 

More recently instead of leukophoresis, a commercially available kit was used for the marrow manipulation. The cells were injected into the hip (7 cases) or the knee (12 cases). The effect was seen as soon as two weeks after the implantation as the relief of pain and improvement in movement. 

A higher contribution of CD45-CD34- CD90+ and CD73+ cells to the implanted inoculum was beneficial for osteoarthritis treatment but not in improvement of vasculature (likely endothelial stem cells). In the inoculum used for regeneration two subpopulations of cells were identified having endothelial or mesenchymal cell markers. Notably the cells having an unique marker and that of stemness potential, were localized in the gate of small forward and side scatters.  

In conclusion, the angiogenic and anti-inflammatory potential of BMMNC has been clinically documented, and the information that different subsets of the cellular inoculum contribute to the clinical outcome opens a new avenue for targeted therapy using subsets of stem cells for optimal application of treatment