Intraspinal transplantation of neurogenin-expressing stem cells generates spinal cord neural progenitors

NEUROBIOLOGY OF DISEASE

卷:46

Article

Lunn, J. Simon¹  Pacut, Crystal¹  Stern, Emily¹  Sakowski, Stacey A.¹  Velkey, J. Matthew²  O'Shea, Sue²  Feldman, Eva L.¹ 

[1] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

关键词: Embryonic stem cells;    Neurogenin1;    Neural specification;    Spinal cord;   

DOI  :  10.1016/j.nbd.2011.12.044

来源: Elsevier

【 摘 要 】

Embryonic stem (ES) cells and their derivatives are an important resource for developing novel cellular therapies for disease. Controlling proliferation and lineage selection, however, are essential to circumvent the possibility of tumor formation and facilitate the safe translation of ES-based therapies to man. Expression of appropriate transcription factors is one approach to direct the differentiation of ES cells towards a specific lineage and stop proliferation. Neural differentiation can be initiated in ES cells by expression of Neurogenin1 (Ngn1). In this study we investigate the effects of controlled Ngn1 expression on mouse ES (mES) cell differentiation in vitro and following grafting into the rat spinal cord. In vitro, Ngn1 expression in mES cells leads to rapid and specific neural differentiation, and a concurrent decrease in proliferation. Similarly transplantation of Ngn1-expressing mES cells into the spinal cord lead to in situ differentiation and spinal precursor formation. These data demonstrate that Ngn1 expression in mES cells is sufficient promote neural differentiation and inhibit proliferation, thus establishing an approach to safely graft ES cells into the spinal cord. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free