6: Ischemic Stroke and Bone Marrow Transplantation
Stroke is the third cause of mortality worldwide and the leading cause of long-term disability in adults. However, there are no neuroprotective or neurorestorative therapies approved for ischemic stroke. Based on animal stroke models, cell therapy is a potentially new treatment for regaining neurological functions after stroke. Autologous bone marrow transplantation has demonstrated efficacy in acute stroke models through different mechanisms, such as attenuation of neuronal death, modulation of inflammatory response and stimulation of neuroplasticity and neoangiogenesis, mainly due to secretion of growth factors and cytokines.
There is a scarcity of experience with bone marrow transplantation in stroke patients. We have performed a pilot phase I/II controlled clinical trial to evaluate the safety and feasibility of intra-arterial bone marrow mononuclear cell (BM-MNC) transplantation. Twenty middle cerebral artery (MCA) stroke patients were included, and the outcomes were assessed blinded to the group assignment. Intra-arterial BM-MNCs were injected between 5 and 9 days after stroke and follow-up was done for up to 6 months. The safety and efficacy endpoints were evaluated and also biological effects of cell therapy in serum changes of growth factors and cytokines were also assessed.
In this trial, a total of 1.58 = 108 CM-MNCs were injected into the ipsilateral MCA cases. There were no serious adverse events related to BM-MNC transplantation and there was also no tumour formation during follow-up. Although no significant differences in neurological outcomes were found between both groups, there was a trend to better the functional outcomes with a higher number of CD34+ cells injected. We have also observed some biological effects after transplantation. After BM-MNC injec tion, a positive correlation between the number of BM-MNCs injected and serum levels at 90 days of GM-CSF and PDGF-BB were found and higher levels of nerve growth factor were detec ted as well, 8 days after transplantation.
Based on recent reports in literature and our experience, bone marrow mononuclear cell transplantation is feasible and safe in the acute-subacute phase of ischemic stroke. Changes in serum levels of growth factors detected after injection of BM-MNC are probably due to the secretory function of these cells in the ischemic environment. New clinical trials are ongoing to further assess dose and timing of this therapy and to elucidate the efficacy BM-MNC transplantation.
