Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Du, Yuanyuan; Liang, Zhen; Wang, Shusen; Sun, Dong; Wang, Xiaofeng; Liew, Soon Yi; Lu, Shuaiyao; Wu, Shuangshuang; Jiang, Yong; Wang, Yaqi; Zhang, Boya; Yu, Wenhai; Lu, Ziwen; Pu, Ying; Zhang, Yun; Long, Haiting; Xiao, Shanshan; Liang, Rui; Zhang, Zhengyuan; Guan, Jingyang; Wang, Jinlin; Ren, Huixia; Wei, Yanling; Zhao, Jialong; Sun, Shicheng; Liu, Tengli; Meng, Gaofan; Wang, Le; Gu, Jiabin; Wang, Tao; Liu, Yinan; Li, Cheng; Tang, Chao; Shen, Zhongyang; Peng, Xiaozhong; Deng, Hongkui

doi:10.1038/s41591-021-01645-7

Cited by 65 publications

(34 citation statements)

References 81 publications

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“…Human PSC-derived pancreatic progenitors could mature into functional β cells when transplanted into mice and eventually reverse diabetes (Kroon et al, 2008 ; Szot et al, 2015 ). Besides the mouse model, a recent report showed that the human PSC-derived β cells could rescue hyperglycemia in non-human primates (Du et al, 2022 ). The pancreatic lineages (pancreatic progenitors or β cells) derived from human PSCs present the potential in cell replacement therapies for diabetes mellitus.…”

Section: Clinical Applications Of Psc-derived Pancreatic Lineagesmentioning

confidence: 99%

Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

Jin

Jiang

2022

Cell Regen

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Pancreatic β cells differentiated from stem cells provide promise for cell replacement therapy of diabetes. Human pluripotent stem cells could be differentiated into definitive endoderm, followed by pancreatic progenitors, and then subjected to endocrinal differentiation and maturation in a stepwise fashion. Many achievements have been made in making pancreatic β cells from human pluripotent stem cells in last two decades, and a couple of phase I/II clinical trials have just been initiated. Here, we overview the major progresses in differentiating pancreatic β cells from human pluripotent stem cells with the focus on recent technical advances in each differentiation stage, and briefly discuss the current limitations as well.

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Section: Clinical Applications Of Psc-derived Pancreatic Lineagesmentioning

confidence: 99%

Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

Jin

Jiang

2022

Cell Regen

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“…To target diabetes caused by single-gene disease in 2020 the study demonstrated that CRISPR-Cas9 correction of diabetes-induced gene variants enhances differentiation of autologous SC-cells, corrects glucose in diabetic mice, and alleviates endoplasmic reticulum and mitochondrial stress in β cells, thereby protecting pancreatic β cells[ 52 ]; (2) IPSCs have very low differentiation efficiency in vitro and may become cancerous. In 2022, Chinese scholar Deng Hongkui's research group[ 53 ] adjusted the in vitro differentiation scheme and realized efficient induction of differentiation, thus making it possible to prepare functional mature islet cells on a large scale in vitro . The research team transplanted islet cells differentiated from IPSCs into diabetic money model, which effectively reversed diabetes in mice, and no tumor-causing phenomenon was observed in all tran splanted mice during the observation period of up to 48 wk.…”

Section: The Progressions In Stem Cell Therapy For Insulin-independen...mentioning

confidence: 99%

Stem cell therapy for insulin-dependent diabetes: Are we still on the road?

Yang¹,

Hu²,

Jiang³

et al. 2022

WJSC

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In insulin-dependent diabetes, the islet β cells do not produce enough insulin and the patients must receive exogenous insulin to control blood sugar. However, there are still many deficiencies in exogenous insulin supplementation. Therefore, the replacement of destroyed functional β cells with insulin-secreting cells derived from functional stem cells is a good idea as a new therapeutic idea. This review introduces the development schedule of mouse and human embryonic islets. The differences between mouse and human pancreas embryo development were also listed. Accordingly to the different sources of stem cells, the important research achievements on the differentiation of insulin-secreting β cells of stem cells and the current research status of stem cell therapy for diabetes were reviewed. Stem cell replacement therapy is a promising treatment for diabetes, caused by defective insulin secretion, but there are still many problems to be solved, such as the biosafety and reliability of treatment, the emergence of tumors during treatment, untargeted differentiation and autoimmunity, etc. Therefore, further understanding of stem cell therapy for insulin is needed.

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“…In a recent study published in Nature Medicine , Du et al 5 describe a novel method for generating large quantities of human iPSC-derived islets and test their function by transplanting them in a nonhuman primate (NHP) model of diabetes. iPSCs were generated from human adipose-derived fibroblasts and used to produce islets.…”

Section: Human Pluripotent Stem-cell-derived Islets Ameliorate Diabet...mentioning

confidence: 99%

Research Highlights

Schroder¹,

Luo²

2022

Transplantation

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Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Cited by 65 publications

References 81 publications

Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

Stem cell therapy for insulin-dependent diabetes: Are we still on the road?

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