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Vol 57, No 1 (2019)
Review paper
Submitted: 2019-02-05
Accepted: 2019-02-06
Published online: 2019-03-11
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In vitro generation of pancreatic β-cells for diabetes treatment. I. β-like cells derived from human pluripotent stem cells

Katarzyna Cierpka-Kmiec1, Agata Wronska2, Zbigniew Kmiec2
DOI: 10.5603/FHC.a2019.0001
·
Pubmed: 30869153
·
Folia Histochem Cytobiol 2019;57(1):1-14.
Affiliations
  1. Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland
  2. Department of Histology, Medical University of Gdansk, Poland

open access

Vol 57, No 1 (2019)
REVIEW
Submitted: 2019-02-05
Accepted: 2019-02-06
Published online: 2019-03-11

Abstract

Diabetes mellitus is a chronic disease that affects hundreds of millions of people worldwide. Type 1 diabetes (T1D) is characterized by the lack of pancreatic β-cells that had been destroyed as a result of an autoimmune response. Therefore, in patients with T1D, the replacement therapy with functional β-cells derived from extrinsic sources could be a preferable option as compared to insulin treatment. Unfortunately, successful transplantation of whole pancreata or pancreatic islets into patients with diabetes is available only to a fraction of them due to the scarcity of donors. The rapid development of cell reprogramming methods made it possible to generate large numbers of human β-like cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). This review describes the basis of in vitro differentiaton protocols of β-like cells that mimic changes of the main signaling pathways during the key stages of human and murine pancreas development, which are described first. During the last 15 years it was found that there are no important differences between hESCs and hiPSCs in their differentiation capacities into β-like cells and the expression profiles of the key transcription factors. The in vitro produced β-like cells are immature as demonstrated by functional tests in rodents and single-cell transcriptomic and proteomic analyses. After the transplantation of the β cell progenitors into immunocompromised diabetic mice, a few weeks have to pass before the increased insulin levels in response to glucose load appear. There is a continuous progress in the development of open-type encapsulation devices which allow the vascularization of the transplanted cells and protect them against host’s immune cells. The results of the first clinical trial of human partially differentiated endocrine progenitors of β cells transplanted into patients with T1D will be published in the year 2019. It is hoped that further improvements in the techniques of large-scale generation of the β-like cells derived from human pluripotent stem cells will bring us closer to their clinical application as a form of cause-directed therapy for people with diabetes.

 

Abstract

Diabetes mellitus is a chronic disease that affects hundreds of millions of people worldwide. Type 1 diabetes (T1D) is characterized by the lack of pancreatic β-cells that had been destroyed as a result of an autoimmune response. Therefore, in patients with T1D, the replacement therapy with functional β-cells derived from extrinsic sources could be a preferable option as compared to insulin treatment. Unfortunately, successful transplantation of whole pancreata or pancreatic islets into patients with diabetes is available only to a fraction of them due to the scarcity of donors. The rapid development of cell reprogramming methods made it possible to generate large numbers of human β-like cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). This review describes the basis of in vitro differentiaton protocols of β-like cells that mimic changes of the main signaling pathways during the key stages of human and murine pancreas development, which are described first. During the last 15 years it was found that there are no important differences between hESCs and hiPSCs in their differentiation capacities into β-like cells and the expression profiles of the key transcription factors. The in vitro produced β-like cells are immature as demonstrated by functional tests in rodents and single-cell transcriptomic and proteomic analyses. After the transplantation of the β cell progenitors into immunocompromised diabetic mice, a few weeks have to pass before the increased insulin levels in response to glucose load appear. There is a continuous progress in the development of open-type encapsulation devices which allow the vascularization of the transplanted cells and protect them against host’s immune cells. The results of the first clinical trial of human partially differentiated endocrine progenitors of β cells transplanted into patients with T1D will be published in the year 2019. It is hoped that further improvements in the techniques of large-scale generation of the β-like cells derived from human pluripotent stem cells will bring us closer to their clinical application as a form of cause-directed therapy for people with diabetes.

 

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Keywords

diabetes; human pancreas development; hESC; hiPSC; in vitro differentiation; transcription factors; β-like cells; β cell replacement

About this article
Title

In vitro generation of pancreatic β-cells for diabetes treatment. I. β-like cells derived from human pluripotent stem cells

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 57, No 1 (2019)

Article type

Review paper

Pages

1-14

Published online

2019-03-11

Page views

5408

Article views/downloads

3484

DOI

10.5603/FHC.a2019.0001

Pubmed

30869153

Bibliographic record

Folia Histochem Cytobiol 2019;57(1):1-14.

Keywords

diabetes
human pancreas development
hESC
hiPSC
in vitro differentiation
transcription factors
β-like cells
β cell replacement

Authors

Katarzyna Cierpka-Kmiec
Agata Wronska
Zbigniew Kmiec

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