2. Academic Validation
  3. Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds

Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds

  • Cell Stem Cell. 2025 Feb 15:S1934-5909(25)00040-2. doi: 10.1016/j.stem.2025.02.001.
Deliang Zhu 1,  Zixin Chen 1,  Kaimin Guo 2,  Qingqiang Xie 3,  Yuxiu Zou 3,  Qizheng Mou 4,  Zhongjun Zhou 5,  Guoxiang Jin 6
Affiliations

Affiliations

  • 1 Guangdong Cardiovascular Institute, Medical Research Institute, School of Basic Medical Science, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 2 Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510627, China.
  • 3 Guangdong Cardiovascular Institute, Medical Research Institute, School of Basic Medical Science, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
  • 4 School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
  • 5 School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China. Electronic address: zhongjun@hku.hk.
  • 6 Guangdong Cardiovascular Institute, Medical Research Institute, School of Basic Medical Science, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. Electronic address: gxjinking@163.com.
PMID: 39999846 DOI: 10.1016/j.stem.2025.02.001
Abstract

Islet organoids derived from pluripotent stem cells offer a promising solution for the shortage of cadaveric donors in diabetes treatment. However, challenges remain in improving their differentiation, viability, functional maturity, and engraftment. Here, we generated improved islet organoids with high viability and functionality by employing extracellular matrix (ECM) hydrogel of decellularized amniotic membrane (dAM). The dAM sheet facilitates islet Organoid engraftment and rapidly restores normoglycemia in diabetic mice, accompanied by increased body weight and augmented Insulin release in response to glucose. Interestingly, collagen VI (Col VI) was identified as a key component of islet niche, enhancing islet cell viability and biological function. Col-VI-based biomimetic ECM recapitulates the native environment and exhibits superior physiological properties. Importantly, the cellular composition and endocrine function of optimized induced pluripotent stem cell (iPSC)-derived islet organoids are comparable with those of human islets. Our findings offer a valuable platform for future endeavors in organoid-transplantation-based therapy of diabetes.

Keywords

biomimetic islet; collagen VI; dAM; decellularized amniotic membrane; diabetes; islet organoid; pancreatic β function and maturation.

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