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DRG 源性神经前体细胞在出生后结肠移植后可分化为功能性肠神经元。

DRG-Derived Neural Progenitors Differentiate into Functional Enteric Neurons Following Transplantation in the Postnatal Colon.

机构信息

1 Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, School of Medicine, Zhejiang University, China.

2 Institute of Translational Medicine, School of Medicine, Zhejiang University, China.

出版信息

Cell Transplant. 2019 Feb;28(2):157-169. doi: 10.1177/0963689718811061. Epub 2018 Nov 15.

Abstract

Cell therapy has great promise for treating gastrointestinal motility disorders caused by intestinal nervous system (ENS) diseases. However, appropriate sources, other than enteric neural stem cells and human embryonic stem cells, are seldom reported. Here, we show that neural progenitors derived from the dorsal root ganglion (DRG) of EGFP mice survived, differentiated into enteric neurons and glia cells, migrated widely from the site of injection, and established neuron-muscle connections following transplantation into the distal colon of postnatal mice. The exogenous EGFP+ neurons were physiologically functional as shown by the activity of calcium imaging. This study shows that that other tissues besides the postnatal bowel harbor neural crest stem cells or neural progenitors that have the potential to differentiate into functional enteric neurons in vivo and can potentially be used for intestinal nerve regeneration. These DRG-derived neural progenitor cells may be a choice for cell therapy of ENS disease as an allograft. The new knowledge provided by our study is important for the development of neural crest stem cell and cell therapy for the treatment of intestinal neuropathy.

摘要

细胞疗法在治疗肠道神经系统 (ENS) 疾病引起的胃肠道动力障碍方面具有巨大的应用前景。然而,除了肠神经干细胞和人胚胎干细胞外,很少有合适的来源被报道。在这里,我们展示了源自 EGFP 小鼠背根神经节 (DRG) 的神经前体细胞可以存活、分化为肠神经元和神经胶质细胞、从注射部位广泛迁移,并在移植到新生小鼠的远端结肠后建立神经元-肌肉连接。外源性 EGFP+神经元具有生理功能,如钙成像活性所示。这项研究表明,除了出生后的肠道外,其他组织还含有神经嵴干细胞或神经前体细胞,它们具有在体内分化为功能性肠神经元的潜力,并可用于肠道神经再生。这些源自 DRG 的神经前体细胞可能是 ENS 疾病同种异体细胞治疗的选择。我们的研究提供了新的知识,对于神经嵴干细胞的发展和细胞治疗肠道神经病变具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15d1/6362519/66e77b6be107/10.1177_0963689718811061-fig1.jpg

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