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

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Published in Transplant international. 2021, vol. 35, 10214
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.
Keywords HUVECsHuman amniotic epithelial cellsPrevascularized iset organoidsRegenerative medicineTissue engineeringΒ cell replacement therapiesAnimalsBioengineeringDiabetes Mellitus, Type 1 / surgeryEndothelial CellsEpithelial Cells / cytologyHuman Umbilical Vein Endothelial Cells / cytologyHumansInsulin / metabolismIslets of Langerhans TransplantationIslets of Langerhans / cytologyMiceOrganoids / physiologyRatsTissue Engineering
PMID: 35185372
PMCID: PMC8842259
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Research groups Laboratoire de biologie des tumeurs gynécologiques et du développement (927)
Création de tissus par bio-ingénieurie et régénération d'organes (1021)
Martinez De Tejada Begona (272)
European Commission: VANGUARD
European Foundation for the Study of Diabetes (EFSD)
Juvenile Diabetes Research Foundation (JDRF): 3-SRA-2020-926-S-B
Shota Rustaveli National Science Foundation: FR-19-19760
Swiss National Science Foundation: 310030_173138
(ISO format)
WASSMER, Charles-Henri et al. Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes. In: Transplant international, 2021, vol. 35, p. 10214. doi: 10.3389/ti.2021.10214 https://archive-ouverte.unige.ch/unige:161622

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Deposited on : 2022-06-22

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