Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury.
Human bone marrow-derived mesenchymal stem cells (hMSCs) are considered a desirable cell source for autologous cell transplantation therapy to treat nervous system injury due to their ability to differentiate into specific cell types and render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. To potentiate their possible trophic effect, hMSCs were induced without genetic modification to adopt characteristics of Schwann cells (SCs), which provide trophic support for regenerating axons. The induced hMSCs (shMSCs) adopted a SC-like morphology and expressed SC-specific proteins including the p75 neurotrophin receptor, which correlated with cell-cycle exit. In addition, shMSCs secreted higher amounts of several growth factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) when compared with uninduced hMSCs. Coculture of shMSCs with Neuro2A cells significantly increased neurite outgrowth and cell proliferation but decreased cell death. Transplantation of shMSCs in an ex vivo model of spinal cord injury dramatically enhanced axonal outgrowth, which was mediated by HGF and VEGF secretion and also decreased cell death. These results demonstrate that shMSCs could serve as an endogenous source of neurotrophic growth factors to facilitate axonal regeneration while at the same time protecting the resident cells at the site of tissue injury. We propose that these induced hMSCs without genetic modification are useful for autologous cell therapy to treat nervous system injury.
Park
Hwan-Woo
HW
Department of Oral Anatomy, Dental Research Institute and School of Dentistry, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea.
Lim
Mi-Jin
MJ
Jung
Heekyung
H
Lee
Seung-Pyo
SP
Paik
Ki-Suk
KS
Chang
Mi-Sook
MS
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D002460:Cell Line; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy
D036341:Intercellular Signaling Peptides and Proteins