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先天性巨结肠症无神经节细胞肠段的施万细胞可生成神经元，用于再生治疗。

Schwann Cells in the Aganglionic Colon of Hirschsprung Disease Can Generate Neurons for Regenerative Therapy.

机构信息

Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China.

出版信息

Stem Cells Transl Med. 2022 Dec 30;11(12):1232-1244. doi: 10.1093/stcltm/szac076.

DOI:10.1093/stcltm/szac076
PMID:36322091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9801298/
Abstract

Cell therapy offers the potential to replace the missing enteric nervous system (ENS) in patients with Hirschsprung disease (HSCR) and to restore gut function. The Schwann cell (SC) lineage has been shown to generate enteric neurons pre- and post-natally. Here, we aimed to isolate SCs from the aganglionic segment of HSCR and to determine their potential to restore motility in the aganglionic colon. Proteolipid protein 1 (PLP1) expressing SCs were isolated from the extrinsic nerve fibers present in the aganglionic segment of postnatal mice and patients with HSCR. Following 7-10 days of in vitro expansion, HSCR-derived SCs were transplanted into the aganglionic mouse colon ex vivo and in vivo. Successful engraftment and neuronal differentiation were confirmed immunohistochemically and calcium activity of transplanted cells was demonstrated by live cell imaging. Organ bath studies revealed the restoration of motor function in the recipient aganglionic smooth muscle. These results show that SCs isolated from the aganglionic segment of HSCR mouse can generate functional neurons within the aganglionic gut environment and restore the neuromuscular activity of recipient mouse colon. We conclude that HSCR-derived SCs represent a potential autologous source of neural progenitor cells for regenerative therapy in HSCR.

摘要

细胞治疗为先天性巨结肠症（HSCR）患者提供了替代缺失的肠神经系统（ENS）并恢复肠道功能的潜力。施万细胞（SC）谱系已被证明在出生前和出生后产生肠神经元。在这里，我们旨在从 HSCR 的无神经节段分离 SC，并确定它们在无神经节结肠中恢复运动功能的潜力。从出生后小鼠和 HSCR 患者无神经节段存在的外生神经纤维中分离出表达蛋白脂质蛋白 1（PLP1）的 SC。在体外扩增 7-10 天后，将 HSCR 来源的 SC 移植到无神经节的小鼠结肠体外和体内。通过免疫组织化学证实了成功的植入和神经元分化，并通过活细胞成像证明了移植细胞的钙活性。器官浴研究显示，受者无神经节平滑肌的运动功能得到恢复。这些结果表明，从 HSCR 小鼠无神经节段分离的 SC 可以在无神经节肠道环境中产生功能性神经元，并恢复受者小鼠结肠的神经肌肉活性。我们得出结论，HSCR 来源的 SC 代表 HSCR 再生治疗中潜在的自体神经祖细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49e3/9801298/5a5bb65b041e/szac076f0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49e3/9801298/cabfa769b421/szac076f0008.jpg
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