Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China.
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Int J Mol Sci. 2021 Sep 7;22(18):9659. doi: 10.3390/ijms22189659.
The development of the enteric nervous system (ENS) is highly modulated by the synchronized interaction between the enteric neural crest cells (ENCCs) and the neural stem cell niche comprising the gut microenvironment. Genetic defects dysregulating the cellular behaviour(s) of the ENCCs result in incomplete innervation and hence ENS dysfunction. Hirschsprung disease (HSCR) is a rare complex neurocristopathy in which the enteric neural crest-derived cells fail to colonize the distal colon. In addition to ENS defects, increasing evidence suggests that HSCR patients may have intrinsic defects in the niche impairing the extracellular matrix (ECM)-cell interaction and/or dysregulating the cellular niche factors necessary for controlling stem cell behaviour. The niche defects in patients may compromise the regenerative capacity of the stem cell-based therapy and advocate for drug- and niche-based therapies as complementary therapeutic strategies to alleviate/enhance niche-cell interaction. Here, we provide a summary of the current understandings of the role of the enteric neural stem cell niche in modulating the development of the ENS and in the pathogenesis of HSCR. Deciphering the contribution of the niche to HSCR may provide important implications to the development of regenerative medicine for HSCR.
肠神经系统（ENS）的发育高度受到肠神经嵴细胞（ENCCs）与肠道微环境中的神经干细胞龛之间同步相互作用的调节。遗传缺陷扰乱了 ENCCs 的细胞行为，导致神经支配不完全，从而导致 ENS 功能障碍。先天性巨结肠（HSCR）是一种罕见的复杂神经嵴病变，其中肠神经嵴衍生细胞未能定殖到远端结肠。除了 ENS 缺陷外，越来越多的证据表明，HSCR 患者的龛位可能存在内在缺陷，损害细胞外基质（ECM）-细胞相互作用，或扰乱控制干细胞行为所必需的细胞龛因子。患者龛位缺陷可能会影响基于干细胞的治疗的再生能力，并提倡基于药物和龛位的治疗作为补充治疗策略，以减轻/增强龛位-细胞相互作用。在这里，我们总结了目前对肠神经干细胞龛在调节 ENS 发育和 HSCR 发病机制中的作用的理解。阐明龛位对 HSCR 的贡献可能对 HSCR 的再生医学发展具有重要意义。
