Transplantation of human bone marrow stromal cell-derived neuroregenrative cells promotes functional recovery after spinal cord injury in mice

被引:0
作者
Mannoji, Chikato [1 ]
Koda, Masao [1 ,2 ]
Kamiya, Koshiro [2 ]
Dezawa, Mari [3 ]
Hashimoto, Masayuki [2 ]
Furuya, Takeo [2 ]
Okawa, Akihiko [2 ]
Takahashi, Kazuhisa [2 ]
Yamazaki, Masashi [4 ]
机构
[1] Chiba Aoba Municipal Hosp, Dept Orthoped Surg, Chiba, Japan
[2] Chiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan
[3] Tohoku Univ, Grad Sch Med, Dept Stem Cell Biol & Histol, Sendai, Miyagi 980, Japan
[4] Univ Tsukuba, Dept Orthoped Surg, Tsukuba, Ibaraki, Japan
关键词
bone marrow stromal cell; NOD/SCID mice; spinal cord injury; transplantation; STEM-CELLS; ADULT-RATS; NEUROTROPHIC FACTORS; DIFFERENTIATE; MECHANISMS; LOCOMOTION; THERAPIES; CONTUSION; REPAIR; BRAIN;
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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/SC1D) 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.
引用
收藏
页码:479 / 488
页数:10
相关论文
共 27 条
[11]   Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells [J].
Fujimoto, Yusuke ;
Abematsu, Masahiko ;
Falk, Anna ;
Tsujimura, Keita ;
Sanosaka, Tsukasa ;
Juliandi, Berry ;
Semi, Katsunori ;
Namihira, Masakazu ;
Komiya, Setsuro ;
Smith, Austin ;
Nakashima, Kinichi .
STEM CELLS, 2012, 30 (06) :1163-1173
[12]   Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells [J].
Garbossa, D. ;
Boido, M. ;
Fontanella, M. ;
Fronda, C. ;
Ducati, A. ;
Vercelli, A. .
NEUROSURGICAL REVIEW, 2012, 35 (03) :293-311
[13]   Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury [J].
Keirstead, HS ;
Nistor, G ;
Bernal, G ;
Totoiu, M ;
Cloutier, F ;
Sharp, K ;
Steward, O .
JOURNAL OF NEUROSCIENCE, 2005, 25 (19) :4694-4705
[14]   Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury [J].
Lu, P ;
Jones, LL ;
Snyder, EY ;
Tuszynski, MH .
EXPERIMENTAL NEUROLOGY, 2003, 181 (02) :115-129
[15]   Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord [J].
McDonald, JW ;
Liu, XZ ;
Qu, Y ;
Liu, S ;
Mickey, SK ;
Turetsky, D ;
Gottlieb, DI ;
Choi, DW .
NATURE MEDICINE, 1999, 5 (12) :1410-1412
[16]   Advances in stem cell therapy for spinal cord injury [J].
Mothe, Andrea J. ;
Tator, Charles H. .
JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (11) :3824-3834
[17]   Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice [J].
Nori, Satoshi ;
Okada, Yohei ;
Yasuda, Akimasa ;
Tsuji, Osahiko ;
Takahashi, Yuichiro ;
Kobayashi, Yoshiomi ;
Fujiyoshi, Kanehiro ;
Koike, Masato ;
Uchiyama, Yasuo ;
Ikeda, Eiji ;
Toyama, Yoshiaki ;
Yamanaka, Shinya ;
Nakamura, Masaya ;
Okano, Hideyuki .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (40) :16825-16830
[18]   Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats [J].
Ogawa, Y ;
Sawamoto, K ;
Miyata, T ;
Miyao, S ;
Watanabe, M ;
Nakamura, M ;
Bregman, BS ;
Koike, M ;
Uchiyama, Y ;
Toyama, Y ;
Okano, H .
JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 69 (06) :925-933
[19]   Function of RNA-binding protein Musashi-1 in stem cells [J].
Okano, H ;
Kawahara, H ;
Toriya, M ;
Nakao, K ;
Shibata, S ;
Imai, T .
EXPERIMENTAL CELL RESEARCH, 2005, 306 (02) :349-356
[20]   Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions [J].
Quertainmont, Renaud ;
Cantinieaux, Dorothee ;
Botman, Olivier ;
Sid, Selim ;
Schoenen, Jean ;
Franzen, Rachelle .
PLOS ONE, 2012, 7 (06)