Neuroprotective effect of bone marrow-derived mononuclear cells promoting functional recovery from spinal cord injury.
Neural cell transplantation, a new therapeutic strategy for replacing injured neural components and obtaining functional recovery, has shown beneficial effects in animal models. Use of this strategy in human patients, however, requires that a number of serious issues be addressed, including ethics, immunorejection, and the therapeutic time window within which the procedure will be effective. Bone marrow-derived mononuclear cells (BM-MNC) are attractive for transplantation because they can be used as an autograft, can be easily collected within a short time period, and do not have to be cultured. In a rat model of spinal cord injury (SCI), we transplanted BM-MNC at 1 h after SCI at Th 8-9 by injecting them into the cerebrospinal fluid (CSF), and investigated the effect of this on neurologic function. In the acute stage of injury, we found a neuroprotective antiapoptotic effect, with an elevated concentration of hepatocyte growth factor in CSF. At 1 week after transplantation, the Basso-Beattie-Bresnahan locomotor score had increased significantly over its base-line value. In the chronic stage of injury, we observed suppressed cavity formation and functional improvement. We conclude that transplantation of BM-MNC after SCI has a remarkable neuroprotective effect in the acute stage of injury, suppressing cavity formation, and contributing to functional recovery. Our results suggest that transplantation of BM-MNC via the CSF is a potentially effective means of enhancing functional recovery after SCI in humans.
Yoshihara
Tomoyuki
T
Department of Anatomy and Neurobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. t-yoshihara@umin.ac.jp
Ohta
Masayoshi
M
Itokazu
Yutaka
Y
Matsumoto
Naoya
N
Dezawa
Mari
M
Suzuki
Yoshihisa
Y
Taguchi
Akihiko
A
Watanabe
Yumi
Y
Adachi
Yasushi
Y
Ikehara
Susumu
S
Sugimoto
Hisashi
H
Ide
Chizuka
C
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000639:trends; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology*; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010243:Paralysis / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
D017228:Hepatocyte Growth Factor