1. Neuroscience Series Transplantation of Bone Marrow Cells in a Focal Ischemia Model (6)
Department of Neurological, Nephrological and Rheumatological Science, Graduate School of Medicine, Nippon Medical School
We describe cell transplantation for experimental brain infarction. Pluripotent embryonic stem (ES) cells, fetal and adult neural stem cells, and bone marrow cells are considered to be possible donor cells for transplantation. In addition, recently established inducible pluripotent stem (iPS) cells are also candidate donor cells. Because an embryo or fetus is required to obtain ES and fetal neural stem cells, obtaining such cells is ethically problematic. Adult neural stem cells are difficult to obtain, because these cells are present in the subventricular zone and the hippocampus. Although iPS cells can be used for autologous transplantation, gene transfection is necessary to produce these cells. Bone marrow cell transplantation has been established as a hematologic treatment. Bone marrow contains pluripotent bone marrow stromal cells (BMSCs) that can be used for autologous transplantation. BMSC transplantation reportedly results in good functional recovery and infarct volume reduction in an experimental stroke model. BMSCs produce various trophic factors, such as vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor, which decrease apoptosis in the ischemic boundary zone. BMSCs require a period of cell culture before transplantation, whereas bone marrow mononuclear cells (BMMCs) can be collected autologously just before administration. This ease of collection may provide a clinical advantage, although BMSCs may have a greater protective potential than do BMMCs. We examined the effects of BMMC transplantation in an experimental stroke model. Autologous BMMCs were obtained from each rat, and animals were subjected to 90 minutes of focal ischemia followed by BMMC administration via the ipsilateral carotid artery or the femoral vein immediately after reperfusion. Infarct volume and motor function were assessed at 24 hours and at 7 days after reperfusion. Infarct volume reduction and good motor function were observed in animals that had undergone intra-arterial BMMC transplantation. BMMCs were labeled with PKH26 before administration, and many PKH26-positive cells were observed within the ischemic hemispheres of rats that had undergone intra-arterial BMMC transplantation. The larger number of transplanted BMMCs in the brain during the early stage of reperfusion may be important for the protective effect. Further investigations are necessary to establish cell transplantation therapy for ischemic stroke.
ϊγεγο 2009; 5(1), 47-52
bone marrow mononuclear cells, bone marrow stromal cells, transplantation, ischemic stroke, neuroprotection
Masayuki Ueda, Divisions of Neurology, Nephrology and Rheumatology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8603, Japan