Preliminary report on the safety, efficacy and functional recovery of spinal cord injury with autologous bone marrow derived mesenchymal stem cells – a clinical trial

摘要

Background: Cell based therapies are increasingly entering into clinical trials in thetreatment of spinal cord lesions as it has been observed to help improve regeneration and spinal cord function.Methods and Results: Transplantation of autologous cultured bone marrow derived stromal cells (BMSCs) in5patients was attempted in the cases of total transectional spinal cord injury with respect to safety, efficacy, therapeutic time window, implantation strategy, method of administrati on, functional improvement. The report on the available data suggests that it is safe, efficacious and resulted in functional recovery in two patients. The follow -up examinations were done at 3,6 and12 months after cell infusion therapy by way of objectiv e assessment in motor function and improvement based on ASIA score. No adverse reactions were encountered during the entire protocol.Conclusions: It is evident that the therapeutic time window, implantation strategy and post transplant care following inju ry will play an important role in Spinal cord Injury Management. BMMNC and BMSC dualistic therapy appears promising for faster healing of the scar and functional improvement. Trials involving a larger populationare warranted before further conclusions can be drawn. Source(s) of support: Global Medical Education & Research Centre, Hyderabad. Introduction Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a potentially useful source of cells for cell repl acement therapy after nervous tissue damage. They are expanded in culture and reintroduced into patients as autografts/allografts. This is a preliminary report on early successful results obtained during treatment offive patients with chronic spinal cor d injury (SCI). In the last decade, adult stem cells have preceded over investigational embryonic stem cell therapy due to their plasticity and possible differentiation into numerous cell types, including neural cells [12345]. The two most important co mmon findings are that the mesenchymal stem cells demonstrate significant promise in tissue regeneration and immune modulation. The limited therapeutic option in the management of severe neurological deficits with the resulting permanent invalidity require s new therapeutic approaches. Autologous bone marrow derived stem cells are ideal candidates for treating SCI in emerging clinical studies, because there are no ethical obstacles to their use, and the health risk for patients with SCI is rather small. Nume rous electrophysiological and histological preclinical studies have revealed that the implantation of stem cells from bone marrow or umbilical cord blood in animal models of SCI results in spared white matter and gray matter, neuronal and axonal regeneration, astrocyte proliferation, myelination, neovascularization, and functional improvement [1678910]. The reports on successful animal model experiments derive the scope of translation to human clinical trials.In this clinical trial, autologous cultured bone marrow derived mesenchymal stem cells were infused at the site of injury; the results of the 12 -month clinical follow -up are described. Material and Methods Ethical approval for this study was obtained from the Institutional Review Board(IRB) and Institutional Ethics Committee (IEC). Patients with traumatic SCI (Total Transectional Injury) with complete motor and sensory disorder were enrolled for the study, and high-risk informed consent was obtained from each patient. The selection and exclusion criteria is summarised in Table.1