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Endoscopically injectable and self-crosslinkable hydrogel-mediated stem cell transplantation for alleviating esophageal stricture after endoscopic submucosal dissection

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Title
Endoscopically injectable and self-crosslinkable hydrogel-mediated stem cell transplantation for alleviating esophageal stricture after endoscopic submucosal dissection
Author(s)
Hyunsoo Chung; Soohwan An; Seung Yeop Han; Jihoon Jeon; Seung-Woo Cho; Yong Chan Lee
Publication Date
2023-05
Journal
Bioengineering and Translational Medicine, v.8, no.3
Publisher
John Wiley and Sons Inc
Abstract
Esophageal stricture after extensive endoscopic submucosal dissection impairs the quality of life of patients with superficial esophageal carcinoma. Beyond the limitations of conventional treatments including endoscopic balloon dilatation and the application of oral/topical corticosteroids, several cell therapies have been recently attempted. However, such methods are still limited in clinical situations and existing setups, and the efficacies are less in some cases since the transplanted cells hardly remain at the resection site for a long time due to swallowing and peristalsis of the esophagus. Thus, a cell transplantation platform directly applicable with clinically established equipment and enabling stable retention of transplanted cells can be a promising therapeutic option for better clinical outcomes. Inspired by ascidians that rapidly self-regenerate, this study demonstrates endoscopically injectable and self-crosslinkable hyaluronate that allows both endoscopic injection in a liquid state and self-crosslinking as an in situ-forming scaffold for stem cell therapy. The pre-gel solution may compatibly be applied with endoscopic tubes and needles of small diameters, based on the improved injectability compared to the previously reported endoscopically injectable hydrogel system. The hydrogel can be formed via self-crosslinking under in vivo oxidative environment, while also exhibiting superior biocompatibility. Finally, the mixture containing adipose-derived stem cells and the hydrogel can significantly alleviate esophageal stricture after endoscopic submucosal dissection (75% of circumference, 5 cm in length) in a porcine model through paracrine effects of the stem cell in the hydrogel, which modulate regenerative processes. The stricture rates on Day 21 were 79.5% ± 2.0%, 62.8% ± 1.7%, and 37.9% ± 2.9% in the control, stem cell only, and stem cell-hydrogel groups, respectively (p < 0.05). Therefore, this endoscopically injectable hydrogel-based therapeutic cell delivery system can serve as a promising platform for cell therapies in various clinically relevant situations. © 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.
URI
https://pr.ibs.re.kr/handle/8788114/13521
DOI
10.1002/btm2.10521
ISSN
2380-6761
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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