期刊
TRANSPLANT INTERNATIONAL
卷 35, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/ti.2021.10214
关键词
regenerative medicine; tissue engineering; beta cell replacement therapies; prevascularized iset organoids; human amniotic epithelial cells; HUVECs
资金
- European Commission (Horizon 2020 Framework Program
- VANGUARD grant) [874700]
- 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]
- Swiss National Science Foundation (SNF) [310030_173138] Funding Source: Swiss National Science Foundation (SNF)
Lack of rapid revascularization and inflammatory attacks contribute to poor outcomes after clinical islet transplantation. In a study using pre-vascularized islet organoids, enhanced in vitro function, better engraftment, and improved vascularization were observed, mainly due to cross-talk between different cell types and upregulation of genes promoting angiogenesis and beta cell function.
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 beta 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 beta cell replacement therapies in more favourable transplantation sites than the liver.
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