胰腺去细胞化支架促进诱导多能干细胞来源的胰岛样组织成熟的研究

Islet transplantation is the best way to cure diabetes, which has the problem of donor shortage and immune rejection. It's urgent to find the suitable transplant materials. Induced pluripotent stem cells (iPSc) have many advantages, such as muti-diffrenciation and no immune rejection, which provides a new direction for the study of islet regeneration. How to promote the differentiation of human iPSc into more mature islet beta cells is the main focus of this study. Therefore, we use three-dimensional decellularized scaffold, in vivo and in vitro, to further study the role of three-dimensional decellularized scaffold microenvironment in the promotion the differentiation of iPSc-derived endoderm cells into islet-like beta cells. This study intends to clarify that decelluarized scaffold can promote the differentiation and maturation of iPSc-derived islet-like beta cells, which can survive in vivo and play the role in regulating blood glucose. At the same time, this study intends to clarify the changes in islet regeneration signal pathway and gene expression and the mechanism in the three-dimensional devascularized scaffold microenvironment promoting cell differentiation and maturation process, which provides the theoretical basis of iPSc-derived islet-like beta cells in clinical islet transplantation to cure islet dysfunction diseases.

胰岛移植是治疗糖尿病的根本方法，但是存在供体短缺和免疫排斥等问题，寻找更加适宜的移植材料是目前需要迫切解决的问题。诱导多能干细胞（iPSc）具有多向分化且无排斥等优点，为胰岛再生研究提供新的方向。如何人为的促进iPSc定向分化为更加成熟的胰岛β样细胞是本研究的重点，因此，我们通过应用去细胞支架三维培养模式，分别在体外和体内水平，深入研究支架三维培养微环境对iPSc来源的特定内胚层细胞分化为胰岛β细胞样细胞所发挥的促进作用。明确去细胞支架培养能够促进iPSc来源的胰岛β样细胞的分化成熟，并且能够在体内存活，发挥调控血糖的生理功能。同时，阐明去细胞支架三维微环境促进细胞分化成熟过程中的胰岛再生相关信号通路和基因表达的改变，明确其机制，从而为iPSc来源的胰岛样组织将来应用于临床胰岛移植，根治胰岛功能障碍性疾病提供理论基础。

胰岛移植是治疗糖尿病的根本方法，但是存在供体短缺和免疫排斥等问题，寻找更加适宜 的移植材料是目前需要迫切解决的问题。诱导多能干细胞(iPSc)具有多向分化且无排斥等优 点，为胰岛再生研究提供新的方向。如何人为的促进iPSc定向分化为更加成熟的胰岛β样细胞 是本研究的重点，因此，我们通过应用去细胞支架三维培养模式，分别在体外和体内水平，深 入研究支架三维培养微环境对iPSc来源的特定内胚层细胞分化为胰岛β细胞样细胞所发挥的促 进作用。明确去细胞支架培养能够促进iPSc来源的胰岛β样细胞的分化成熟，并且能够在体内 存活，发挥调控血糖的生理功能。同时，阐明去细胞支架三维微环境促进细胞分化成熟过程中 的胰岛再生相关信号通路和基因表达的改变，明确其机制，从而为iPSc来源的胰岛样组织将来 应用于临床胰岛移植，根治胰岛功能障碍性疾病提供理论基础。