title: Evaluation of the survival of bone marrow-derived mononuclear cells and the growth factors produced upon intramedullary transplantation in rat models of acute spinal cord injury.
abstract: Intramedullary bone marrow-derived mononuclear cell (BM-MNC) transplantation has demonstrated neuroprotective effects in the chronic stage of spinal cord injury (SCI). However, no previous study has evaluated its effects in the acute stage, even though cell death occurs mainly within 1week after injury in all neuronal cells. Moreover, the mechanism underlying these effects remains unclear. We aimed to investigate the survival of intramedullary transplanted allogeneic BM-MNCs and the production of growth factors after transplantation to clarify the therapeutic potential of intramedullary transplanted BM-MNCs and their protective effects in acute SCI. Sprague-Dawley rats were subjected to traumatic SCI and received intramedullary transplantation of EGFP(+)BM-MNCs (n=6), BM-MNCs (n=10), or solvent (n=10) immediately after injury. To evaluate the transplanted BM-MNCs and their therapeutic effects, immunohistochemical evaluations were performed at 3 and 7days post-injury (DPI). BM-MNCs were observed at the injected site at both 3 (683±83 cells/mm(2)) and 7 DPI (395±64 cells/mm(2)). The expression of hepatocyte growth factor was observed in approximately 20% transplanted BM-MNCs. Some BM-MNCs also expressed monocyte chemotactic protein-1 or vascular endothelial growth factor. The demyelinated area and number of cleaved caspase-3-positive cells were significantly smaller in the BM-MNC-transplanted group at 3 DPI. Hindlimb locomotor function was significantly improved in the BM-MNC-transplanted group at 7 DPI. These results suggest that intramedullary transplantation of BM-MNCs is an efficient method for introducing a large number of growth factor-producing cells that can induce neuroprotective effects in the acute stage of SCI.
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Arai
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan. Electronic address: yasuji@nvlu.ac.jp.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.affiliation: Laboratory of Veterinary Pathology, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Michishita
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kanno
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yogo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka 530-8507, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1, Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D053148:Caspase 3 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D009043:Motor Activity; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3
keywords: Apoptosis; Bone marrow-derived mononuclear cells; Green fluorescent protein; Hepatocyte growth factor; Intramedullary transplantation; Spinal cord injury