Transplantation of mesenchymal stem cells enhances axonal outgrowth and cell survival in an organotypic spinal cord slice culture.
Mesenchymal stem cells (MSCs) have demonstrated a measurable therapeutic effect following transplantation into animal models of spinal cord injury. However, the mechanism(s) by which transplanted cells promote nerve regeneration and/or functional recovery remains indeterminate. Several studies have suggested that MSCs promote tissue repair via secretion of trophic factors, but delineating the effect of such factors is difficult due to the complexity of the in vivo systems. Therefore, we developed an organotypic spinal cord slice culture system that can be sustained for sufficient periods of time in vitro to evaluate nerve regeneration as an ex vivo model of spinal cord injury. Using this model, we demonstrate that treatment of lumbar slices of spinal cord with lysolecithin induced a significant degree of cell death and demyelination of nerve fibers, but that these effects were ameliorated to a significant extent following co-culture of slices with human MSCs (hMSCs). The results indicate that transplanted hMSCs alter the tissue microenvironment in a way that promotes survival of endogenous cells, including injured neurons, immature oligodendrocytes and oligodendrocyte progenitor cells. This ex vivo culture system represents a useful tool to further dissect the mechanism(s) by which MSCs promote regeneration of injured nervous tissue.
Department of Oral Anatomy, Dental Research Institute & School of Dentistry, College of Veterinary Medicine, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea.
Jung-Sun
JS
Cho
Hwan-Woo
HW
Park
Sang-Kyu
SK
Park
Sangho
S
Roh
Soo-Kyung
SK
Kang
Ki-Suk
KS
Paik
Mi-Sook
MS
Chang
D000818:Animals; D001369:Axons / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D018920:Coculture Techniques; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D045164:Mesenchymal Stem Cell Transplantation; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology*