Signaling Molecules Regulating Pancreatic Endocrine Development from Pluripotent Stem Cell Differentiation
Signaling Molecules Regulating Pancreatic Endocrine Development from Pluripotent Stem Cell Differentiation
复制标题
DOI：
10.3390/ijms21165867
复制
发表时间：
2020-08
影响因子：
5.6
通讯作者：
Hui Huang;Taylor N Bader;Sha Jin
中科院分区：
文献类型：
--
作者：
Hui Huang;Taylor N Bader;Sha Jin
糖尿病是全球死亡的主要原因之一。目前，供体胰腺是人类胰岛的唯一来源，这对供应造成了极大的限制。因此，开发可再生胰岛用于糖尿病研究和治疗势在必行。迄今为止，已经进行了广泛的努力，从人多能干细胞获得胰岛素分泌细胞，并取得了实质性的成功。然而，功能性胰岛类器官的体外生成仍然是一个挑战，部分原因是我们对控制干细胞自组装功能性胰岛的分化途径所不可或缺的信号分子的理解不足。由于这一过程依赖于各种信号分子来指导分化途径，以及模拟体内生理条件的培养微环境，本文重点介绍了细胞外基质蛋白，生长因子，信号分子和微环境，促进从人多能干细胞产生具有生物学功能的胰腺内分泌细胞。信号通路参与逐步分化，指导干细胞的进展，进入内分泌谱系进行了讨论。预期能够产生具有与天然成人胰岛相当的激素释放能力的胰岛类器官的方案的开发用于临床应用、疾病建模和糖尿病研究。
Diabetes is one of the leading causes of death globally. Currently, the donor pancreas is the only source of human islets, placing extreme constraints on supply. Hence, it is imperative to develop renewable islets for diabetes research and treatment. To date, extensive efforts have been made to derive insulin-secreting cells from human pluripotent stem cells with substantial success. However, the in vitro generation of functional islet organoids remains a challenge due in part to our poor understanding of the signaling molecules indispensable for controlling differentiation pathways towards the self-assembly of functional islets from stem cells. Since this process relies on a variety of signaling molecules to guide the differentiation pathways, as well as the culture microenvironments that mimic in vivo physiological conditions, this review highlights extracellular matrix proteins, growth factors, signaling molecules, and microenvironments facilitating the generation of biologically functional pancreatic endocrine cells from human pluripotent stem cells. Signaling pathways involved in stepwise differentiation that guide the progression of stem cells into the endocrine lineage are also discussed. The development of protocols enabling the generation of islet organoids with hormone release capacities equivalent to native adult islets for clinical applications, disease modeling, and diabetes research are anticipated.