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World J Stem Cells. Mar 26, 2026; 18(3): 113900
Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.113900
Allogeneic myoblast cell sheet transplantation for esophageal wall reinforcement
Takahiro Enjoji, Shinichiro Kobayashi, Daisuke Miyamoto, Shinichiro Ogawa, Hanako Tetsuo, Akihiko Soyama, Tomohiko Adachi, Susumu Eguchi, Kengo Kanetaka
Takahiro Enjoji, Shinichiro Kobayashi, Daisuke Miyamoto, Shinichiro Ogawa, Hanako Tetsuo, Akihiko Soyama, Tomohiko Adachi, Susumu Eguchi, Kengo Kanetaka, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
Author contributions: Enjoji T, Kobayashi S, and Eguchi S contributed to the study conception and design; Kobayashi S, Miyamoto D, Soyama A, Adachi T, Kanetaka K, and Eguchi S provided administrative support; Enjoji T, Kobayashi S, Miyamoto D, Tetsuo H, and Eguchi S provided experimental support; Enjoji T and Kobayashi S contributed to the collection and assembly of data; Enjoji T, Kobayashi S, Ogawa S, and Miyamoto D provided the data analysis and interpretation; Enjoji T, Kobayashi S, Kanetaka K, and Eguchi S performed the manuscript writing. All authors read and approved the final version of the manuscript.
Supported by the JSPS Grant-in-Aid for Scientific Research C, No. 24K11935; and AMED, No. 25ym0126811j0004.
Institutional animal care and use committee statement: This study was approved by the Nagasaki University Animal Experiment Committee (Approval No. 220324-1) and implemented accordingly.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.
Corresponding author: Shinichiro Kobayashi, MD, PhD, Associate Professor, FACS, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki 852-8501, Japan. skobayashi1980@gmail.com
Received: September 7, 2025
Revised: October 25, 2025
Accepted: February 3, 2026
Published online: March 26, 2026
Processing time: 200 Days and 6.7 Hours
Abstract
BACKGROUND

Using muscle flaps for reinforcing weakened tissue is an established technique that is widely used in the treatment of anastomotic leakage and intractable fistulas after esophagectomy. However, it has certain limitations including invasiveness and compromised cosmetic outcomes. Several studies have reported the efficacy of myoblast cell sheet transplantation in the prevention of digestive fistulas by reinforcing the gastrointestinal wall. However, its structural integrity and temporal changes after transplantation remain unclear.

AIM

To clarify the behavior of myoblast cell sheets and histological progression of wall reconstruction and alternative muscle flaps.

METHODS

Myoblast cell sheets were cultured for 7-10 days. In rats 67% of the abdominal esophageal muscle layers were removed. Myoblast cell sheets were transplanted to the resected site in the transplantation group while the control group received no transplantation. Body weight gain and histological evaluation were performed at weeks 1, 2, and 4 after surgery.

RESULTS

The fabricated myoblast cell sheets formed multilayered cell structures 50-μm thick with desmin-positive cells and Ki67-positive cells (Ki67 rate: 39.6% ± 6.8%). All esophageal wall resections and immediately subsequent myoblast cell sheet transplants were successful. Peritonitis was not observed in either group. At 4 weeks postoperatively, the transplant group showed a significantly higher rate of weight gain than the control group (67.8% ± 17.3% vs 44.7% ± 9.6%, P < 0.05). The transplantation group showed proliferating desmin-positive myoblasts 1 week postoperative and significantly thicker esophageal wall (1174.0 ± 177.0 μm vs 267.6 ± 257.6 μm, P < 0.05). The esophageal muscle layer thickness was not significantly different between the groups at 2 weeks and 4 weeks postoperative.

CONCLUSION

The short-term histological efficacy of allogeneic myoblast cell sheet transplantation for esophageal wall reinforcement was confirmed in an established rat model.

Keywords: Myoblast; Esophagus; Muscle layer; Cell sheet; Tissue repair

Core Tip: Muscle flaps are widely used for reinforcing esophageal defects. However, they are invasive and cosmetically unfavorable. Myoblast cell sheets are less invasive, although their in vivo behavior is unclear. In a rat model of esophageal muscle layer defects, transplanted myoblast sheets formed multilayered desmin-positive and Ki67-positive structures and transiently increased esophageal wall thickness compared with controls that did not receive a myoblast cell sheet transplantation at 1 week. These findings suggested that myoblast cell sheets provide short-term reinforcement, highlighting their potential as muscle flap alternatives while underscoring the need for further evaluation.