title: Transplantation of human bone marrow stromal cell-derived neuroregenrative cells promotes functional recovery after spinal cord injury in mice.
abstract: Transplantation of bone marrow stromal cells (BMSCs) for spinal cord injury (SCI) has been shown to improve functional outcome. BMSCs can be easily obtained from bone marrow aspirate and have fewer problems in the clinical application for human SCI from the ethical and legal points of view. Recently, we produced cells with neural stem and/or progenitor cell property and neural regeneration supporting capacity from human bone marrow stromal cells (human bone marrow stromal cell-derived neuroregenerative cells: hBMSC-NRs). The aim of the present study was to clarify the effectiveness of transplantation of hBMSC-NRs to injured spinal cord of severe combined immunodeficiency (NOD/SCID) mice. Neurite outgrowth assay of PC-12 cells was performed. One week after a T9-level contusion SCI, hBMSCs or hBMSC-NRs were transplanted into the spinal cord. After the transplantation, functional and histological examinations were performed. Conditioned media of hBMSC-NRs significantly promoted the neurite outgrowth of PC-12 cells in vitro. Transplanted hBMSC-NRs survived in the injured spinal cord 8 weeks after SCI. Immunohistochemistry revealed that the density of serotonin-positive fibers of the transplanted group was significantly higher than that of the control group at the epicenter and caudal segment to the injured site. The recovery of hind limb function of the hBMSC-NRs group was significantly better than that of the control group. In conclusion, hBMSC-NRs can be one of the realistic candidates for cell transplantation therapy for human SCI.
authors.affiliation: Department of Orthopedic Surgery, Chiba Aoba Municipal Hospital, Chiba, Japan; masaokod@gmail.com.
authors.forename: Chikato
authors.initials: C
authors.lastname: Mannoji
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Koshiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Furuya
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016716:PC12 Cells; D050543:Phosphoglycerate Dehydrogenase / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000601:surgery*; D018800:Thy-1 Antigens / Q000378:metabolism; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D018800:Thy-1 Antigens; D014746:Vimentin; D012701:Serotonin; D050543:Phosphoglycerate Dehydrogenase