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Cell Rep. 2018 May 8;23(6):1620-1629. doi: 10.1016/j.celrep.2018.03.123.

Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation.

Author information

1
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
2
Clinical Islet Laboratory, University of Alberta, Edmonton, AB, Canada.
3
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Advanced Medical Research Center, Yokohama City University, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Division of Gastroenterology, Hepatology & Nutrition, Developmental Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; Institute of Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: takanori.takebe@cchmc.org.
4
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Advanced Medical Research Center, Yokohama City University, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan. Electronic address: rtanigu@yokohama-cu.ac.jp.

Abstract

Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by "self-condensation" culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation.

KEYWORDS:

islet transplantation; organoid; tissue engineering; tissue-based therapy; vascularization

PMID:
29742420
DOI:
10.1016/j.celrep.2018.03.123
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