Decellularized Tissue Matrix Enhances Self-Assembly of Islet Organoids from Pluripotent Stem Cell Differentiation,ACS Biomaterials Science & Engineering

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Decellularized Tissue Matrix Enhances Self-Assembly of Islet Organoids from Pluripotent Stem Cell Differentiation
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-05-21 , DOI: 10.1021/acsbiomaterials.0c00088
Huanjing Bi ₁ , Soujanya S Karanth ₁ , Kaiming Ye _{1,

2} , Roland Stein ₃ , Sha Jin _{1,

2}

Affiliation

Regenerating human islet organoids from stem cells remains a significant challenge because of our limited knowledge on cues essential for developing the endocrine organoids in vitro. In this study, we discovered that a natural material prepared from a decellularized rat pancreatic extracellular matrix (dpECM) induces the self-assembly of human islet organoids during induced pluripotent stem cell (iPSC) pancreatic differentiation. For the first time, we demonstrated that the iPSC-derived islet organoids formed in the presence of the dpECM are capable of glucose-responsive secretion of both insulin and glucagon, two major hormones that maintain blood glucose homeostasis. The characterization of the organoids revealed that the organoids consisted of all major endocrine cell types, including α, β, δ, and pancreatic polypeptide cells, that were assembled into a tissue architecture similar to that of human islets. The exposure of iPSCs to the dpECM during differentiation resulted in considerably elevated expression of key pancreatic transcription factors such as PDX-1, MAFA, and NKX6.1 and the production of all major hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide from stem cell-derived organoids. This study highlights the importance of natural, bioactive biomaterials for building microenvironments crucial to regenerating islet organoids from stem cells.

中文翻译：

脱细胞组织基质增强多能干细胞分化胰岛类器官的自组装

从干细胞再生人类胰岛类器官仍然是一项重大挑战，因为我们对体外开发内分泌类器官所必需的线索的了解有限。在这项研究中，我们发现由脱细胞大鼠胰腺细胞外基质 (dpECM) 制备的天然材料在诱导多能干细胞 (iPSC) 胰腺分化过程中诱导人胰岛类器官的自组装。我们首次证明，在 dpECM 存在的情况下形成的 iPSC 衍生胰岛类器官能够对胰岛素和胰高血糖素进行葡萄糖响应性分泌，这两种主要激素可维持血糖稳态。类器官的表征表明，类器官由所有主要的内分泌细胞类型组成，包括 α、β、δ 和胰多肽细胞，它们被组装成类似于人类胰岛的组织结构。iPSCs 在分化过程中暴露于 dpECM 导致关键胰腺转录因子（如 PDX-1、MAFA 和 NKX6.1）的表达显着升高，并产生所有主要激素，包括胰岛素、胰高血糖素、生长抑素和胰腺多肽干细胞衍生的类器官。这项研究强调了天然生物活性生物材料对于构建微环境的重要性，该微环境对于从干细胞中再生胰岛类器官至关重要。来自干细胞衍生类器官的胰高血糖素、生长抑素和胰多肽。这项研究强调了天然生物活性生物材料对于构建微环境的重要性，该微环境对于从干细胞中再生胰岛类器官至关重要。来自干细胞衍生类器官的胰高血糖素、生长抑素和胰多肽。这项研究强调了天然生物活性生物材料对于构建微环境的重要性，该微环境对于从干细胞中再生胰岛类器官至关重要。

更新日期：2020-07-13

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