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Scientific article
Open access
English

Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes

Published inTransplant international, vol. 35, 10214
Publication date2022-01-21
First online date2022-01-21
Abstract

Lack of rapid revascularization and inflammatory attacks at the site of transplantation contribute to impaired islet engraftment and suboptimal metabolic control after clinical islet transplantation. In order to overcome these limitations and enhance engraftment and revascularization, we have generated and transplanted pre-vascularized insulin-secreting organoids composed of rat islet cells, human amniotic epithelial cells (hAECs), and human umbilical vein endothelial cells (HUVECs). Our study demonstrates that pre-vascularized islet organoids exhibit enhanced in vitro function compared to native islets, and, most importantly, better engraftment and improved vascularization in vivo in a murine model. This is mainly due to cross-talk between hAECs, HUVECs and islet cells, mediated by the upregulation of genes promoting angiogenesis (vegf-a) and β cell function (glp-1r, pdx1). The possibility of adding a selected source of endothelial cells for the neo-vascularization of insulin-scereting grafts may also allow implementation of β cell replacement therapies in more favourable transplantation sites than the liver.

eng
Keywords
  • HUVECs
  • Human amniotic epithelial cells
  • Prevascularized iset organoids
  • Regenerative medicine
  • Tissue engineering
  • Β cell replacement therapies
  • Animals
  • Bioengineering
  • Diabetes Mellitus, Type 1 / surgery
  • Endothelial Cells
  • Epithelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans Transplantation
  • Islets of Langerhans / cytology
  • Mice
  • Organoids / physiology
  • Rats
  • Tissue Engineering
Funding
Citation (ISO format)
WASSMER, Charles-Henri et al. Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes. In: Transplant international, 2022, vol. 35, p. 10214. doi: 10.3389/ti.2021.10214
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Article (Published version)
Secondary files (2)
Identifiers
ISSN of the journal0934-0874
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Technical informations

Creation02/22/2022 9:06:00 AM
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