Cerecellgram-Stroke, bone marrow-derived mesenchymal stem cells for treatment of ischemic stroke

Cerecellgram-Stroke (STARTING-2) is a product comprised of autologous bone marrow-derived mesenchymal stem cells (MSCs), preconditioned with serum from the ischemic stroke patient before transplantation. Preliminary results from a clinical trial showed that intravenous infusion of MSCs was found to be safe throughout the short-term follow-up period in ischemic stroke patients . A subsequent trial, conducted in a larger population size, reported a 100% reduction in mortality rates among this patient population following MSCs transplantation when compared to the control group. No significant side effects were observed over the 5 years following transplantation of MSCs cultured in FBS-containing medium. However, the use of fetal calf serum (FCS) or fetal bovine serum (FBS) in cell culture has raised concerns relating to risks of prion transmission and stimulation of immunogenicity. In preclinical studies, MSCs from a rat stroke model was expanded either using serum from the same rat stroke model or using FBS. MSC expansion using rat stroke serum was more rapid, and decreased cell death/senescence, while increased trophic factor secretion, and migration capacity was observed. Therefore, phase III of STARTING-2 clinical trials will use autologous ischemic serum for ex vivo culture expansion, prior to cell infusion into the ischemic stroke patients. The study will assess whether transplantation of autologous MSCs expanded in autologous serum obtained during the acute phase of stroke, is associated with better outcomes than standard treatment. Efficacy of MSC therapy will be determined by serial assessment of detailed motor function and imaging biomarkers.