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World J Stem Cells. Aug 26, 2026; 18(8): 123046
Published online Aug 26, 2026. doi: 10.4252/wjsc.123046
Published online Aug 26, 2026. doi: 10.4252/wjsc.123046
Induced pluripotent stem cells in Hirschsprung disease: Modeling, mechanisms, and translational challenges
Yuan-Xiang Qiu, Zheng-Ke Zhi, Xin-Tao Zhang, Chun-Xia Du, Jie Tang, Hong-Xing Li, Wei-Bing Tang, Department of Pediatric Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu Province, China
Yu-Mu Leng, Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Co-first authors: Yuan-Xiang Qiu and Zheng-Ke Zhi.
Co-corresponding authors: Hong-Xing Li and Wei-Bing Tang.
Author contributions: Qiu YX and Zhi ZK contributed equally to this manuscript as co-first authors. Qiu YX and Zhi ZK performed the literature search, analyzed the data, and drafted and revised the manuscript; Leng YM was responsible for data visualization and the creation of figures; Zhang XT assisted with literature collection and data verification; Du CX assisted in data sorting and manuscript proofreading; Tang J participated in result collation and logical revision of the manuscript; Li HX and Tang WB contributed equally to this manuscript as co-corresponding authors. Li HX and Tang WB supervised the project, were responsible for funding acquisition, and critically revised the manuscript for important intellectual content. All authors have read and approved the final manuscript.
AI contribution statement: ChatGPT (OpenAI) was used as an assistive tool for language polishing, translation, and writing support in portions of the authors’ responses to the reviewers. The entirety of the responses was not AI-generated. All scientific content, interpretation of evidence, responses to reviewer comments, manuscript revisions, and final wording were independently reviewed, verified, and approved by the authors. AI tools were not used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions. The authors take full responsibility and accountability for all content of this manuscript, including any portions for which ChatGPT was used as an assistive technology.
Supported by the National Natural Science Foundation of China, No. 82001590 and No. 82270540.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Hong-Xing Li, MD, PhD, Associate Professor, Department of Pediatric Surgery, Children’s Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing 210008, Jiangsu Province, China. hx8817@njmu.edu.cn
Received: May 11, 2026
Revised: June 17, 2026
Accepted: July 13, 2026
Published online: August 26, 2026
Processing time: 102 Days and 15.8 Hours
Revised: June 17, 2026
Accepted: July 13, 2026
Published online: August 26, 2026
Processing time: 102 Days and 15.8 Hours
Core Tip
Core Tip: Patient-derived induced pluripotent stem cell (iPSC) platforms provide human models for linking Hirschsprung disease (HSCR)-associated genetic backgrounds with enteric neural crest cell (ENCC) developmental phenotypes and tissue-level interactions. This review summarizes iPSC platform establishment, two-dimensional ENCC models, recombined and bioengineered gut systems, drug screening, and cell-based regenerative strategies. We emphasize genetic complexity, reproducibility, functional maturation, electrophysiological validation, and translational feasibility. Current iPSC-based HSCR models are most useful for mechanistic investigation and preclinical development, whereas drug screening and cell therapy remain exploratory.