Coculturing human islets with proangiogenic support cells to improve islet revascularization at the subcutaneous transplantation site
| Autor: | Jan de Boer, Clemens van Blitterswijk, Marten A. Engelse, Aart A. van Apeldoorn, Jacqueline R. M. Plass, Marcel Karperien, Eelco J.P. de Koning, Maaike Hanegraaf, Mijke Buitinga, Dirk Jan Cornelissen, Françoise Carlotti, Karolina Janeczek Portalska |
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| Přispěvatelé: | Faculty of Science and Technology, Developmental BioEngineering, Hubrecht Institute for Developmental Biology and Stem Cell Research, CTR, RS: MERLN - Complex Tissue Regeneration (CTR), CBITE, RS: MERLN - Cell Biology - Inspired Tissue Engineering (CBITE) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell type endocrine system Biomedical Engineering Neovascularization Physiologic Bioengineering Research Support Biochemistry Umbilical vein Biomaterials Islets of Langerhans 03 medical and health sciences 0302 clinical medicine In vivo Human Umbilical Vein Endothelial Cells Journal Article Humans Non-U.S. Gov't geography geography.geographical_feature_category Chemistry Research Support Non-U.S. Gov't Mesenchymal stem cell Mesenchymal Stem Cells Original Articles Islet 22/4 OA procedure Coculture Techniques In vitro Transplantation 030104 developmental biology 030220 oncology & carcinogenesis Immunology Cancer research Pancreatic islet transplantation |
| Zdroj: | Tissue engineering. Part A, 22(3 en 4), 375-385. Mary Ann Liebert Inc. Tissue engineering. Part A, 22(3-4), 375-85. Mary Ann Liebert Inc. Tissue Engineering: Parts A, B, and C, 22(3-4), 375-385. MARY ANN LIEBERT, INC Tissue Engineering. Part A, 22(3-4), 375. Mary Ann Liebert Inc. Tissue Engineering, 22(3-4), 375-385. Mary Ann Liebert Inc. |
| ISSN: | 1937-3341 2152-4947 |
| Popis: | While subcutaneous tissue has been proposed as a clinically relevant site for pancreatic islet transplantation, a major issue of concern remains, which is its poor vascular state. In an effort to overcome this limitation, we present an efficient and reproducible method to form human composite islets (CIs) with proangiogenic cell types in a controlled manner using nonadherent agarose microwell templates. In this study, we assessed the three-dimensional structure, function, and angiogenic potential of human CIs with human mesenchymal stromal cells (hMSCs), with or without human umbilical vein endothelial cells (HUVECs), and preconditioned hMSCs (PC-hMSCs) in EGM-2 under shear stress. Distinct cellular rearrangements could be observed in CIs, but islet functionality was maintained. In vitro angiogenesis assays found significantly enhanced sprout formation in case of CIs. In particular, the number of sprouts emanating from CIs with PC-hMSCs was significantly increased compared to other conditions. Subsequent in vivo assessment confirmed the proangiogenic potential of CIs. However, in contrast to our in vitro angiogenesis assays, CIs with hMSCs and HUVECs exhibited a higher in vivo angiogenic potential compared to control islets or islets combined with hMSCs or PC-hMSCs. These findings highlight the importance and necessity of verifying in vitro studies with in vivo models to reliably predict, in this case, revascularization outcomes. Regardless, we demonstrate here the therapeutic potential of CIs with proangiogenic support cells to enhance islet revascularization at a clinically relevant, although poorly vascularized, transplantation site. |
| Databáze: | OpenAIRE |
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