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Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

 Kyujin Hwang  ;  Kwangsoo Jung  ;  Il-Sun Kim  ;  Miri Kim  ;  Jungho Han  ;  Joohee Lim  ;  Jeong Eun Shin  ;  Jae-Hyung Jang  ;  Kook In Park 
 EXPERIMENTAL NEUROBIOLOGY, Vol.28(6) : 679-696, 2019 
Journal Title
Issue Date
Cell-based therapy ; Glial cell line-derived neurotrophic factor ; Mechanical allodynia ; Neural stem/progenitor cells ; Paraplegia ; Spinal cord injuries
Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell linederived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNFhNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Ri(김미리) ORCID logo https://orcid.org/0000-0002-0380-1677
Kim, Il-Sun(김일선) ORCID logo https://orcid.org/0000-0003-4033-4323
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Shin, Jeong Eun(신정은) ORCID logo https://orcid.org/0000-0002-4376-8541
Lim, Joo Hee(임주희) ORCID logo https://orcid.org/0000-0003-4376-6607
Jung, Kwang Soo(정광수) ORCID logo https://orcid.org/0000-0001-7365-7247
Han, Jung Ho(한정호) ORCID logo https://orcid.org/0000-0001-6661-8127
Hwang, Kyujin(황규진) ORCID logo https://orcid.org/0000-0001-5193-5154
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