Abstract 45: Intracerebral Transplantation of Autologous Bone Marrow Stem Cell (BMSC) Against Acute Ischemic Stroke, Preliminary Data of Phase 1 Clinical Trial (RAINBOW Project)
Background: Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Prior studies have demonstrated that bone marrow stromal cells (BMSC) have therapeutic potential against stroke. In this study, we investigated the use of autologous BMSC transplantation for acute ischemic stroke through direct transplantation route with several new aspects including cell labeling and tracking, socioecomonic analysis using QALY, and the use of human platelet lysate (PL) instead of fetal bovine serum. This study is called the Research on Advanced Intervention using Novel Bone marrOW stem cell (RAINBOW, UNIN ID: UMIN000026130). Methods/Design: RAINBOW is a phase 1, open-label, uncontrolled, dose-response study, with the primary aim to determine the safety of the autologous BMSC administered to the patients with acute ischemic stroke. Estimated enrollment is 7 patients suffering severe neurological deficits. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each patient 15 days or later from the onset, and BMSCs are cultured with allogeneic PL and are labeled with superparamagnetic iron oxide for cell tracking using magnetic resonance imaging (MRI). BMSCs are stereotactically administered around the area of infarction in the subacute phase. Each patient will be administered a dose of 20 or 50 million cells. Neurological scoring, MRI for cell tracking, 18 F-fuorodeoxyglucose positron emission tomography, and 123 I-Iomazenil single photon emission computed tomography will be performed throughout 1 year after the administration. Results: 6 patients have successfully finished cell transplantation, and there was no severe adverse event in any of the patient during surgical and follow-up period. Favorable motor recoveries are seen in 5 of 6 patients, and cell engraftment and migration to ischemic site was also observed by magnetic resonance imaging. Discussion: This is a first-in-human trial to use labelled BMSC to the patients with acute ischemic stroke. Intracerebral transplantation of autologous BMSC is safe and well tolerated. Moreover, it is expected that the bio-imaging techniques can clarify the therapeutic mechanisms.