PMID- 31731179 OWN - NLM STAT- MEDLINE DCOM- 20200602 LR - 20200602 IS - 1876-7753 (Electronic) IS - 1873-5061 (Linking) VI - 41 DP - 2019 Dec TI - Simulated microgravity-cultured mesenchymal stem cells improve recovery following spinal cord ischemia in rats. PG - 101601 LID - S1873-5061(19)30231-4 [pii] LID - 10.1016/j.scr.2019.101601 [doi] AB - Spinal cord ischemia is a potential complication of thoracoabdominal aortic surgery that may induce irreversible motor disability. We investigated the therapeutic efficacy of simulated microgravity-cultured mesenchymal stem cell (MSC) injection following spinal cord ischemia-reperfusion injury. Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), normal gravity-cultured MSC (MSC-1 G), and simulated microgravity-cultured MSC (MSC-MG) groups. Spinal cord ischemia was induced by transient balloon occlusion of the thoracic aorta, which was followed immediately by PBS or MSC injection into the left carotid artery. Hindlimb motor function was evaluated by the Basso-Beattie-Bresnahan (BBB) scale. Spinal cords were removed 1, 3, or 7 days post-injury for immunohistochemical staining and Western blot analysis. One day post-injury, a few infiltrating inflammatory cells and small vacuoles were observed without significant group differences, followed over several days by progressive spinal cord degeneration. Glial fibrillary acidic protein (GFAP)-positive (reactive) astrocyte numbers were increased in all three groups, and brain-derived neurotrophic factor (BDNF) was colocalized with GFAP-positive cells in spinal ventral horn. Animals in the MSC-MG group demonstrated greater BDNF-positive astrocyte numbers, reduced caspase-3-positive cell numbers, and superior motor recovery. Microgravity-cultured MSC-based therapy may improve functional recovery following spinal ischemia-reperfusion injury by promoting astrocytic BDNF release, thereby preventing apoptosis. CI - Copyright (c) 2019 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Kurose, Tomoyuki AU - Kurose T AD - Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Takahashi, Shinya AU - Takahashi S AD - Department of Cardiovascular Surgery, Hiroshima University Hospital, Hiroshima, Japan. FAU - Otsuka, Takashi AU - Otsuka T AD - Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Nakagawa, Kei AU - Nakagawa K AD - Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Imura, Takeshi AU - Imura T AD - Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. FAU - Sueda, Taijiro AU - Sueda T AD - Hiroshima City Medical Association-administered Hiroshima City Aki Hospital, Hiroshima, Japan. FAU - Yuge, Louis AU - Yuge L AD - Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: ryuge@hiroshima-u.ac.jp. LA - eng PT - Journal Article DEP - 20191015 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 SB - IM MH - Allografts MH - Animals MH - Ischemia/metabolism/pathology/*therapy MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - *Recovery of Function MH - Spinal Cord/blood supply/*metabolism/pathology MH - Spinal Cord Diseases/metabolism/pathology/*therapy MH - *Weightlessness OTO - NOTNLM OT - Apoptosis OT - Astrocyte OT - Brain-derived neurotrophic factor OT - Ischemia-reperfusion injury OT - Microgravity OT - Motor function OT - Spinal cord EDAT- 2019/11/16 06:00 MHDA- 2020/06/03 06:00 CRDT- 2019/11/16 06:00 PHST- 2019/04/03 00:00 [received] PHST- 2019/09/14 00:00 [revised] PHST- 2019/09/23 00:00 [accepted] PHST- 2019/11/16 06:00 [pubmed] PHST- 2020/06/03 06:00 [medline] PHST- 2019/11/16 06:00 [entrez] AID - S1873-5061(19)30231-4 [pii] AID - 10.1016/j.scr.2019.101601 [doi] PST - ppublish SO - Stem Cell Res. 2019 Dec;41:101601. doi: 10.1016/j.scr.2019.101601. Epub 2019 Oct 15.