Sensitivity study for the key parameters in heterospheroid preparation with insulin-secreting beta-cells and mesenchymal stem cells

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dc.authoridErdal Karaöz / 0000-0002-9992-833Xen_US
dc.authorscopusidErdal Karaöz / 7003448087
dc.authorwosidErdal Karaöz / IXE-6677-2023
dc.contributor.authorBal, Tuğba
dc.contributor.authorİnceoğlu, Yasemin
dc.contributor.authorKaraöz, Erdal
dc.contributor.authorKizilel, Seda
dc.date.accessioned2020-08-30T20:06:32Z
dc.date.available2020-08-30T20:06:32Z
dc.date.issued2019
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractThe outcome of islet transplantation in clinics has been determined by the success of tissue engraftment. The strong immune attack that occurs upon transplantation of beta-cells plays a central role as this attack results in the failure of transplanted tissue. To improve tissue engraftment, deleterious effects of immune reactions should be minimized for Pull function and survival. Here, we report a systematic analysis of the effect of insulin-secreting beta-cell (MIN6) and mesenchymal stem cell (MSC) number and size on the function of beta-cells and present immune protection potential of heterospheroid structures through MSCs and synthetic scaffolds. We prepared 3D heterospheroids with MSCs and MIN6 cells through a hanging-drop approach. To precisely estimate the influence of critical parameters on heterospheroid size and insulin secretion function of beta-cells, we prepared heterospheroids using two independent input variables: (i) initial cell number in each droplet and (ii) MIN6:MSC ratio. We studied the influence of initial cell numbers of 200 and 500, and six different MIN6:MSC ratios (1:0, 0:1, 1:1, 2:1, 5:1, and 10:1) for the preparation of heterospheroids through the hanging drop. Next, we used PEG hydrogels as a semipermeable physical barrier to improve immune protection from cytokines. Through encapsulation of our heterospheroids within PEG hydrogel, we were able to observe sustained beta-cell survival and insulin secretion despite exposure of heterospheroids with proinflammatory cytokines. Insulin secretion was further promoted with glucagon like peptide-1 (GLP-1) incorporation within PEG hydrogel structure. This study is significant to demonstrate the synergistic effects of MIN6-MSC and scaffold-MIN6 interactions and to improve therapeutic efficacy of islet transplantation. Overall, this study comprehensively presents the optimum conditions for the preparation of MIN6-MSC spheroids, utilizes MSCs and GLP-1 functional PEG hydrogels as a scaffold to retain insulin secretion function and further demonstrates protection of heterospheroids exposed to proinflammatory cytokines.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) under 1001-Scientific and Technological Research Projects Funding ProgramTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [MAG 113M232]; Koc University Seed Fund [SF.00028]; TUBITAK-BIDEBTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Presidency of Turkey, Presidency of Strategy and Budgeten_US
dc.description.sponsorshipThis study is supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under 1001-Scientific and Technological Research Projects Funding Program (MAG 113M232) and Koc University Seed Fund SF.00028. T.B. is supported by TUBITAK-BIDEB. The authors gratefully acknowledge use of the services and facilities of the Koc University Research Center for Surface Science (KUYTAM) and Koc University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.en_US
dc.identifier.citationBal, T., Inceoglu, Y., Karaoz, E., & Kizilel, S. (2019). Sensitivity Study for the Key Parameters in Heterospheroid Preparation with Insulin-Secreting beta-Cells and Mesenchymal Stem Cells. ACS BIOMATERIALS SCIENCE & ENGINEERING, 5(10), 5229–5239. https://doi.org/10.1021/acsbiomaterials.9b00570en_US
dc.identifier.doi10.1021/acsbiomaterials.9b00570en_US
dc.identifier.endpage5239en_US
dc.identifier.issn2373-9878en_US
dc.identifier.issue10en_US
dc.identifier.pmid33455228en_US
dc.identifier.scopus2-s2.0-85072638461en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage5229en_US
dc.identifier.urihttps://doi.org/10.1021/acsbiomaterials.9b00570
dc.identifier.urihttps://hdl.handle.net/20.500.12713/546
dc.identifier.volume5en_US
dc.identifier.wosWOS:000490658800033en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKaraöz, Erdalen_US
dc.language.isoenen_US
dc.publisherAmer Chemical Socen_US
dc.relation.ispartofAcs Biomaterials Science & Engineeringen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectMin6en_US
dc.subjectMscen_US
dc.subjectPeg Hydrogelen_US
dc.subjectGlp-1en_US
dc.subjectInsulin Secretionen_US
dc.subjectCytokine Attacken_US
dc.subjectImmune Protectionen_US
dc.titleSensitivity study for the key parameters in heterospheroid preparation with insulin-secreting beta-cells and mesenchymal stem cellsen_US
dc.typeArticleen_US

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