In Vivo Differentiation of Stem Cell-derived Human Pancreatic Progenitors to Treat Type 1 Diabetes
- PMID: 32844324
- DOI: 10.1007/s12015-020-10018-5
In Vivo Differentiation of Stem Cell-derived Human Pancreatic Progenitors to Treat Type 1 Diabetes
Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the loss of the pancreatic β-cells. The autoimmune destruction of the β-cells causes the loss of insulin production from the islets of the pancreas, resulting in the loss of blood glucose regulation. This loss of regulation, if not treated, can lead to a plethora of long-term complications in patients. Subsequently, T1DM patients rely on the administration of exogenous insulin sources to maintain their blood glucose levels. In this review, we summarize the history of T1DM therapy and current treatment options. Although treatments for T1DM have progressed substantially, none of the available treatment options allow the patient to live autonomously. Therefore, the challenge to develop a therapy that will fully reverse the disease still remains. A promising field of T1DM therapies is cell replacement therapies derived from human pluripotent stem cells. Here, we specifically review studies that employ stem-cell derived pancreatic progenitors transplanted for in vivo differentiation/maturation and discuss, in detail, the complications that arise post transplantation, including heterogeneity, graft immaturity, and host foreign bodyresponse. We also discuss efforts to induce human stem cell-derived mature β-cells in vitro and compare strategies regarding transplantation of pancreatic progenitors versus mature β-cells cells. Finally, we review key approaches that address critical limitations of in vivo progenitor differentiation including vascularization, oxygenation, and transplant location. The field of islet replacement therapy has made tremendous progress in the last two decades. If the strengths and limitations of the field continue to be identified and addressed, future studies will lead to an ideal treatment for T1DM. Graphical abstract.
Keywords: Beta cells; Cell therapy; In vivo; Islet cell transplantation; Islets; Pancreatic endoderm; Pancreatic progenitors; Pluripotent stem cells; Type 1 diabetes mellitus.
Similar articles
-
Transplantation of human dental pulp stem cells in streptozotocin-induced diabetic rats.Anat Sci Int. 2020 Sep;95(4):523-539. doi: 10.1007/s12565-020-00550-2. Epub 2020 May 31. Anat Sci Int. 2020. PMID: 32476103
-
Current progress in stem cell therapy for type 1 diabetes mellitus.Stem Cell Res Ther. 2020 Jul 8;11(1):275. doi: 10.1186/s13287-020-01793-6. Stem Cell Res Ther. 2020. PMID: 32641151 Free PMC article. Review.
-
Human Induced Pluripotent Stem Cells in the Curative Treatment of Diabetes and Potential Impediments Ahead.Adv Exp Med Biol. 2019;1144:25-35. doi: 10.1007/5584_2018_305. Adv Exp Med Biol. 2019. PMID: 30569414 Review.
-
Harnessing Proliferation for the Expansion of Stem Cell-Derived Pancreatic Cells: Advantages and Limitations.Front Endocrinol (Lausanne). 2021 Feb 25;12:636182. doi: 10.3389/fendo.2021.636182. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 33716986 Free PMC article. Review.
-
In vitro generation of pancreatic β-cells for diabetes treatment. I. β-like cells derived from human pluripotent stem cells.Folia Histochem Cytobiol. 2019;57(1):1-14. doi: 10.5603/FHC.a2019.0001. Epub 2019 Mar 14. Folia Histochem Cytobiol. 2019. PMID: 30869153 Review.
Cited by
-
p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells.Stem Cell Rev Rep. 2023 May;19(4):942-952. doi: 10.1007/s12015-023-10509-1. Epub 2023 Jan 28. Stem Cell Rev Rep. 2023. PMID: 36707464 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical