Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke

BackgroundIschemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke.MethodsThe study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47–64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130).FindingsAll seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1–8 and 0–2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1–6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site.ConclusionsIntracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation.FundingThis work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).