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Highly feasible procedure for laparoscopic transplantation of cell sheets under pneumoperitoneum in porcine model

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Abstract

Introduction

Cell sheet technology is one of the most successful methodologies in regenerative medicine. Various applications of cell sheets have been introduced in first-in-human studies in several clinical fields. When transplanting a cell sheet into internal organs, a relatively large incision is required for delivery due to difficulty handling the sheet. We developed a laparoscopic delivery procedure for safe and easy transplantation of cell sheets in a porcine model.

Methods

Pneumoperitoneum was established by inflation with CO2. First, to increase the strength during handling, fibrin was sprayed onto the surface of the cell sheet, and then a myoblast sheet was placed onto the newly developed carrier. The sheets were pinched with laparoscopic forceps to insert into the abdominal cavity through the laparoscopic port. Myoblast sheets were then applied to the surface of the liver, colon, small intestine, and stomach, and procedure times were measured. At three days post transplantation, a histopathological examination was performed to confirm engraftment of the sheet. The function and engraftment were also analyzed in a duodenal endoscopic submucosal dissection (ESD) model.

Results

The fibrin-processed myoblast sheet was able to be managed with conventional laparoscopic forceps without breaking. Despite the drastic change in air pressure by passing through the laparoscopic port, the sheets suffered no apparent damage. The transplantation procedure times did not markedly differ among transplant sites. A histopathological examination revealed thin-layered, desmin-positive cells at each transplant site. With transplantation following ESD, the engrafted myoblast sheets effectively prevented delayed perforation.

Conclusions

Our procedure is simple, and the system involves a carrier made of medically fit silicon, commercially available fibrin glue and conventional laparoscopic forceps. Our procedure is a powerful tool for laparoscopical cell sheet transplantation.

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Author information

Authors and Affiliations

  1. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Shun Yamaguchi, Shinichiro Kobayashi, Yusuke Sakai & Susumu Eguchi

  2. Tissue Engineering and Regenerative Therapeutics in Gastrointestinal Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Kengo Kanetaka, Yasuhiro Maruya & Miki Higashi

  3. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 8528501, Japan

    Keiichi Hashiguchi & Kazuhiko Nakao

  4. Terumo Corporation, 2-44-1 Hatagaya Shibuya-ku, Tokyo, 1510072, Japan

    Fumiya Oohashi

Authors
  1. Shun Yamaguchi
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  2. Kengo Kanetaka
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  5. Shinichiro Kobayashi
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Contributions

All authors have read and approved the manuscript. SK, YS, AM, and FO developed a prototype of the devices. SY, MK, TI, and YM performed cell sheet transplantation using the devices in pigs and mainly edited the manuscripts. SY and YM contributed equally to the first author. KK supervised the research project. KH and AN participated in the discussion. SE approved the final submission of this manuscript.

Corresponding author

Correspondence to Kengo Kanetaka.

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Disclosures

Drs. Shun Yamaguchi, Shinichiro Kobayashi, Keiichi Hashiguchi, Yusuke Sakai, Kazuhiko Nakao, and Susumu Eguchi have no conflicts of interest or financial ties to disclose. The laboratory which Drs. Kengo Kanetaka, Yasuhiro Maruya, and Miki Higashi belong to received funding for cooperative research in cell sheet from the TERUMO Company. Mr. Fumiya Oohashi belongs to the TERUMO Company.

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Yamaguchi, S., Kanetaka, K., Maruya, Y. et al. Highly feasible procedure for laparoscopic transplantation of cell sheets under pneumoperitoneum in porcine model. Surg Endosc 36, 3911–3919 (2022). https://doi.org/10.1007/s00464-021-08708-3

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  • DOI: https://doi.org/10.1007/s00464-021-08708-3

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