title: Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.
abstract: Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Jiagang
authors.initials: J
authors.lastname: Zhao
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Cho
authors.forename: Hong
authors.initials: H
authors.lastname: Ouyang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.forename: Jiun
authors.initials: J
authors.lastname: Do
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002470:Cell Survival; D017690:Cell Transplantation; D002490:Central Nervous System / Q000378:metabolism*; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000166:cytology*; D054259:Neural Tube / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013119:Spinal Cord Injuries / Q000628:therapy; D013234:Stem Cells / Q000166:cytology
chemical_list: D049452:Green Fluorescent Proteins