Yoshihara Eiji
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States.
David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
Front Cell Dev Biol. 2022 Apr 26;10:854604. doi: 10.3389/fcell.2022.854604. eCollection 2022.
Generation of three-dimensional (3D)-structured functional human islets is expected to be an alternative cell source for cadaveric human islet transplantation for the treatment of insulin-dependent diabetes. Human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer infinite resources for newly synthesized human islets. Recent advancements in hPSCs technology have enabled direct differentiation to human islet-like clusters, which can sense glucose and secrete insulin, and those islet clusters can ameliorate diabetes when transplanted into rodents or non-human primates (NHPs). However, the generated hPSC-derived human islet-like clusters are functionally immature compared with primary human islets. There remains a challenge to establish a technology to create fully functional human islets , which are functionally and transcriptionally indistinguishable from cadaveric human islets. Understanding the complex differentiation and maturation pathway is necessary to generate fully functional human islets for a tremendous supply of high-quality human islets with less batch-to-batch difference for millions of patients. In this review, I summarized the current progress in the generation of 3D-structured human islets from pluripotent stem cells and discussed the importance of adapting physiology for functional human islet organogenesis and possible improvements with environmental cues.
生成三维（3D）结构的功能性人胰岛有望成为尸体人胰岛移植的替代细胞来源，用于治疗胰岛素依赖型糖尿病。人多能干细胞（hPSC），如人胚胎干细胞（hESC）和人诱导多能干细胞（hiPSC），为新合成的人胰岛提供了无限资源。hPSC技术的最新进展已能够直接分化为人胰岛样簇，其可感知葡萄糖并分泌胰岛素，并且这些胰岛簇在移植到啮齿动物或非人类灵长类动物（NHP）中时可改善糖尿病。然而，与原代人胰岛相比，所生成的hPSC来源的人胰岛样簇在功能上并不成熟。建立一种技术以创建与尸体人胰岛在功能和转录上无差异的完全功能性人胰岛仍然是一项挑战。了解复杂的分化和成熟途径对于生成完全功能性人胰岛至关重要，以便为数百万患者提供大量高质量且批次间差异较小的人胰岛。在本综述中，我总结了从多能干细胞生成3D结构人胰岛的当前进展，并讨论了适应生理学以实现功能性人胰岛器官发生的重要性以及利用环境线索可能做出的改进。
