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Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes.

ABSTRACT: Maintaining long-term euglycemia after intraportal islet transplantation is hampered by the considerable islet loss in the peri-transplant period attributed to inflammation, ischemia and poor angiogenesis. Here, we show that viable and functional islet organoids can be successfully generated from dissociated islet cells (ICs) and human amniotic epithelial cells (hAECs). Incorporation of hAECs into islet organoids markedly enhances engraftment, viability and graft function in a mouse type 1 diabetes model. Our results demonstrate that the integration of hAECs into islet cell organoids has great potential in the development of cell-based therapies for type 1 diabetes. Engineering of functional mini-organs using this strategy will allow the exploration of more favorable implantation sites, and can be expanded to unlimited (stem-cell-derived or xenogeneic) sources of insulin-producing cells.

SUBMITTER: Lebreton F

PROVIDER: S-EPMC6776618 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes.

Lebreton Fanny F Lavallard Vanessa V Bellofatto Kevin K Bonnet Romain R Wassmer Charles H CH Perez Lisa L Kalandadze Vakhtang V Follenzi Antonia A Boulvain Michel M Kerr-Conte Julie J Goodman David J DJ Bosco Domenico D Berney Thierry T Berishvili Ekaterine E

Nature communications 20191003 1

Maintaining long-term euglycemia after intraportal islet transplantation is hampered by the considerable islet loss in the peri-transplant period attributed to inflammation, ischemia and poor angiogenesis. Here, we show that viable and functional islet organoids can be successfully generated from dissociated islet cells (ICs) and human amniotic epithelial cells (hAECs). Incorporation of hAECs into islet organoids markedly enhances engraftment, viability and graft function in a mouse type 1 diabe ...[more]

PMID: 31582751

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Project description:BackgroundEvidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined.AimIn the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study.Material and methodsTwo blocks of synthetic bone substitute (?0.14 cm(3)), alone or engineered with 1×10(6) ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses.Results and conclusionsThe obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch-on the expression of a specific bone-related protein (osteocalcin, OCN) when transplanted into host tissues.

Dataset Information

Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes.

Publications

Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes.

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