Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Surg Today. 2024 Sep;54(9):977-994. doi: 10.1007/s00595-023-02741-6. Epub 2023 Sep 5.
Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.
先天性巨结肠（HSCR）及其相关疾病（AD-HSCR）常因肠神经病变、间质病变和肌病导致严重蠕动不良。值得注意的是，累及小肠的 HSCR、孤立性神经节细胞减少症、慢性特发性假性肠梗阻和巨膀胱-小结肠-肠蠕动不良综合征预后不良。最终，对于难治性病例需要进行小肠移植（SBTx），但尽管手术技术和管理有所进步，其侵袭性仍很高，结果并不理想。因此，再生疗法已成为一种潜在的治疗方法，包括对受影响区域的肠神经系统、间质和平滑肌进行再生。我们综述了用于管理 HSCR 和 AD-HSCR 的最新再生治疗方法，包括使用肠神经祖细胞、胚胎干细胞、诱导多能干细胞和间充质干细胞作为细胞来源、受体肠的微环境和移植方法。还讨论了这些治疗方法的未来展望。
