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논문 기본 정보

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학술저널
저자정보
천경진 (가톨릭대학교(성의교정)) 박헌석 (가톨릭대학교(성의교정)) 이은영 (가톨릭대학교) 김민정 (가톨릭대학교) 유영혜 (가톨릭대학교(성의교정)) 이마리 (가톨릭대학교) 김지원 (가톨릭대학교) 윤건호 (가톨릭대학교)
저널정보
대한당뇨병학회 Diabetes and Metabolism Journal Diabetes and Metabolism Journal Vol.46 No.5
발행연도
2022.9
수록면
677 - 688 (12page)
DOI
10.4093/dmj.2021.0202

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Background: Neonatal porcine pancreatic cell clusters (NPCCs) have been proposed as an alternative source of β cells for islet transplantation because of their low cost and growth potential after transplantation. However, the delayed glucose lowering effect due to the immaturity of NPCCs and immunologic rejection remain as a barrier to NPCC’s clinical application. Here, we demonstrate accelerated differentiation and immune-tolerant NPCCs by <i>in vitro</i> chemical treatment and microencapsulation.Methods: NPCCs isolated from 3-day-old piglets were cultured in F-10 media and then microencapsulated with alginate on day 5. Differentiation of NPCCs is facilitated by media supplemented with activin receptor-like kinase 5 inhibitor II, triiodothyronine and exendin-4 for 2 weeks. Marginal number of microencapsulated NPCCs to cure diabetes with and without differentiation were transplanted into diabetic mice and observed for 8 weeks.Results: The proportion of insulin-positive cells and insulin mRNA levels of NPCCs were significantly increased <i>in vitro</i> in the differentiated group compared with the undifferentiated group. Blood glucose levels decreased eventually after transplantation of microencapsulated NPCCs in diabetic mice and normalized after 7 weeks in the differentiated group. In addition, the differentiated group showed nearly normal glucose tolerance at 8 weeks after transplantation. In contrast, neither blood glucose levels nor glucose tolerance were improved in the undifferentiated group. Retrieved graft in the differentiated group showed greater insulin response to high glucose compared with the undifferentiated group.Conclusion: <i>in vitro</i> differentiation of microencapsulated immature NPCCs increased the proportion of insulin-positive cells and improved transplant efficacy in diabetic mice without immune rejection.

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