Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Department of Developmental Biology, University of Science and Culture, Tehran, Iran.
J Cell Physiol. 2019 Jun;234(6):9564-9576. doi: 10.1002/jcp.27644. Epub 2018 Oct 26.
Organoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance maturation of PP by assembly of three-dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell derivatives including ES-derived pancreatic duodenal homeobox 1 (PDX1) early PP, mesenchymal stem cells, and endothelial cells at an optimized cell ratio, on Matrigel. The PO was placed in a 3D-printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicated that, in contrast to corresponding early PP transplants, 3D PO developed more vascularization as indicated by greater area and number of vessels, a higher number of insulin-positive cells and improvement of human C-peptide secretions. Based on our findings, PO-derived β cells could be considered a novel strategy to study human β-cell development, novel therapeutics, and regenerative medicine for diabetes.
类器官可以被视为一种有益的工具，可用于发现糖尿病的新疗法，和/或促进胰腺祖细胞 (PP) 向 β 细胞成熟。在这里，我们设计了一种策略，通过组装三维 (3D) 胰腺类器官 (PO) 来增强 PP 的成熟，该 PO 包含人类胚胎干细胞 (ES) 细胞衍生物，包括 ES 衍生的胰腺十二指肠同源盒 1 (PDX1)、早期 PP、间充质干细胞和内皮细胞，以优化的细胞比例在 Matrigel 上。将 PO 放置在 3D 打印的组织陷阱中，并异位植入免疫缺陷小鼠的腹腔中，在那里停留 90 天。我们的结果表明，与相应的早期 PP 移植相比，3D PO 发育出更多的血管化，表现为血管面积和数量增加，胰岛素阳性细胞数量增加，人 C 肽分泌改善。基于我们的发现，PO 衍生的 β 细胞可以被视为研究人类 β 细胞发育、新型治疗方法和糖尿病再生医学的一种新策略。
