Transplantation of bone marrow stromal cells for peripheral nerve repair.
Cell transplantation using bone marrow stromal cells (BMSCs) to alleviate neurological deficits has recently become the focus of research in regenerative medicine. Evidence suggests that secretion of various growth-promoting substances likely plays an important role in functional recovery against neurological diseases. In an attempt to identify a possible mechanism underlying the regenerative potential of BMSCs, this study investigated the production and possible contribution of neurotrophic factors by transected sciatic nerve defect in a rat model with a 15 mm gap. Cultured BMSCs became morphologically homogeneous with fibroblast-like shape after ex vivo expansion. We provided several pieces of evidence for the beneficial effects of implanted fibroblast-like BMSCs on sciatic nerve regeneration. When compared to silicone tube control animals, this treatment led to (i) improved walking behavior as measured by footprint analysis, (ii) reduced loss of gastrocnemius muscle weight and EMG magnitude, and (iii) greater number of regenerating axons within the tube. Cultured fibroblast-like BMSCs constitutively expressed trophic factors and supporting substances, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), collagen, fibronectin, and laminin. The progression of the regenerative process after BMSC implantation was accompanied by elevated expression of neurotrophic factors at both early and later phases. These results taken together, in addition to documented Schwann cell-like differentiation, provide evidence indicating the strong association of neurotrophic factor production and the regenerative potential of implanted BMSCs.
Chen
Chun-Jung
CJ
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan. cjchen@vghtc.gov.tw
Ou
Yen-Chuan
YC
Liao
Su-Lan
SL
Chen
Wen-Ying
WY
Chen
Shih-Yun
SY
Wu
Ching-Wen
CW
Wang
Chun-Chiang
CC
Wang
Wen-Yi
WY
Huang
Yong-San
YS
Hsu
Shan-Hui
SH
D000818:Animals; D001369:Axons / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D003714:Denervation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009929:Organ Size; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000473:pathology; D012584:Sciatic Nerve / Q000601:surgery*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D016326:Extracellular Matrix Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins