Zhang BL, Kobayashi S, Li LY, Li TY, Ogawa S, Miyamoto D, Hasegawa K, Yamaguchi S, Adachi T, Eguchi S, Kanetaka K. From mesenchymal stem cells to myoblast cell sheets: A next-generation regenerative concept for fistulizing Crohn’s disease. World J Stem Cells 2026; 18(8): 121648 [DOI: 10.4252/wjsc.121648]
Corresponding Author of This Article
Shinichiro Kobayashi, MD, PhD, FACS, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. skobayashi1980@gmail.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bo-Lin Zhang, Shinichiro Kobayashi, Lu-Yang Li, Tian-Yang Li, Shinichiro Ogawa, Daisuke Miyamoto, Kayo Hasegawa, Shun Yamaguchi, Tomohiko Adachi, Susumu Eguchi, Kengo Kanetaka, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
Co-corresponding authors: Shinichiro Kobayashi and Kengo Kanetaka.
Author contributions: Zhang BL and Kobayashi S drafted and edited the manuscript and approved the final version; Ogawa S and Adachi T edited the section on “Pathogenesis of Crohn’s disease”; Ogawa S and Miyamoto D edited the section on “Structural and myogenic limitations of mesenchymal stem cells”; Li LY and Li TY edited the section on “Myoblasts”; Kobayashi S and Hasegawa K contributed to writing and revising the section on “Cell sheet technology”; Yamaguchi S and Adachi T contributed to editing of the section on “Fibrosis and structural remodeling”; Eguchi S and Kanetaka K conceived the study, supervised its overall design, and approved the final manuscript. Kobayashi S and Kanetaka K served as co-corresponding authors and contributed equally to the overall supervision, conceptual development, critical revision, and final approval of the manuscript. Kobayashi S is designated as the corresponding author responsible for communication with the journal during the submission, peer-review, and publication processes.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research C, No. 24K11935; Japan Agency for Medical Research and Development, No. 25ym0126811j0004.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Shinichiro Kobayashi, MD, PhD, FACS, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. skobayashi1980@gmail.com
Received: March 31, 2026 Revised: May 19, 2026 Accepted: June 15, 2026 Published online: August 26, 2026 Processing time: 143 Days and 3.4 Hours
Abstract
Crohn’s disease is a chronic relapsing inflammatory bowel disorder characterized by impaired healing and a high risk of fistula formation. Although biologic therapies effectively suppress inflammation, durable tissue repair remains difficult to achieve because of incomplete structural regeneration. Cell sheet technology, a scaffold-free cell delivery platform that preserves extracellular matrix integrity, offers improved cell retention, sustained paracrine activity, and enhanced tissue integration compared with conventional cell suspension. Preclinical studies across multiple organ systems have indicated that both mesenchymal stem cell and myoblast cell sheets promote angiogenesis and inflammation modulation. However, mesenchymal stem cell-based approaches predominantly induce regulatory repair with a limited capacity for structural reconstruction. In contrast, myoblast cell sheets possess intrinsic myogenic potential, enabling direct muscle layer regeneration and functional restoration of the skeletal muscle. This review discusses recent advances in cell sheet technology for Crohn’s disease and highlights myoblast cell sheets as a promising reconstructive strategy for fistulizing diseases.
Core Tip: Crohn’s disease fistulas remain a clinical challenge because current therapies mainly suppress inflammation without restoring the damaged tissue’s architecture. This review highlights cell sheet technology as a scaffold-free regenerative platform with superior cell retention, extracellular matrix preservation, and sustained paracrine activity. While mesenchymal stem cell therapies mainly provide regulatory repair, myoblast cell sheets add intrinsic myogenic potential, enabling reconstruction of the disrupted muscle layer and functional tissue recovery. By shifting the therapeutic goal from inflammation control to structural regeneration, myoblast cell sheets may offer a next-generation strategy for the durable repair of complex Crohn’s disease fistulas.
