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The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy.

ABSTRACT: Diabetes is a complex metabolic disorder of carbohydrate metabolism, characterized by high blood glucose levels either due to an absolute deficiency of insulin secretion or an ineffective response of cells to insulin, a hormone synthetized by β-cells in the pancreas. Despite the current substantial progress of new drugs and strategies to prevent and treat diabetes, we do not understand precisely the exact cause of the failure and impairment of β-cells. Therefore, there is an urgent need to find new methods to restore β-cells. In recent years, pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC) can serve as an ideal alternative source for the pancreatic β-cells. In this review, we systematically summarize the current progress and protocols of generating pancreatic β-cells from human PSCs. Meanwhile, we also discuss some challenges and future perspectives of human PSCs treatments for diabetes.

SUBMITTER: Wang X

PROVIDER: S-EPMC9365963 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy.

Wang Xin X Gao Mengxi M Wang Yali Y Zhang Yucheng Y

Frontiers in endocrinology 20220728

Diabetes is a complex metabolic disorder of carbohydrate metabolism, characterized by high blood glucose levels either due to an absolute deficiency of insulin secretion or an ineffective response of cells to insulin, a hormone synthetized by β-cells in the pancreas. Despite the current substantial progress of new drugs and strategies to prevent and treat diabetes, we do not understand precisely the exact cause of the failure and impairment of β-cells. Therefore, there is an urgent need to find ...[more]

PMID: 35966093

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Project description:Background Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. Methods BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Results Flow cytometric analysis revealed that BASCs represented ~?7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Conclusions Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.

Dataset Information

The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy.

Publications

The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy.

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