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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Perspective Article

Can Functionally Mature Islet β-Cells be Derived from Pluripotent Stem Cells? A Step Towards Ready-To-Use β-Cells in Type 1 Diabetes

Author(s): Bishnu K. Khand* and Ramesh R. Bhonde

Volume 16, Issue 3, 2021

Published on: 21 June, 2020

Page: [231 - 237] Pages: 7

DOI: 10.2174/1574888X15666200621171726

Abstract

Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for the treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer’s disease, etc. PSCderived pancreatic islet β-cells appear to be a promising therapy for type 1 diabetic patients with impaired β-cell function. Several protocols have been developed to derive β-cells from PSCs. However, these protocols produce β-like cells that show low glucose stimulated insulin secretion (GSIS) function and mirror GSIS profile of functionally immature neonatal β-cells. Several studies have documented a positive correlation between the sirtuins (a family of ageing-related proteins) and the GSIS function of adult β-cells. We are of the view that the GSIS function of PSC-derived β-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the β-cell development and inclusion of the sirtuin activators and inhibitor cocktail (specific to a developmental stage) in the present protocols may help us derive functionally mature, ready-to-use β- cells in-vitro making them suitable for transplantation in type 1 diabetes.

Keywords: Pluripotent Stem Cells (PSCs), Pancreatic islet β-cells, Glucose stimulated insulin secretion (GSIS), Sirt1, Type 1 diabetes, Uncoupling Protein2 (UCP2).

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[1]
Standl E, Khunti K, Hansen TB, Schnell O. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol 2019; 26(2_suppl): 7-14.
[2]
Röder P V, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis Exp Mol Med 2016; 48(November 2015): e219
[http://dx.doi.org/10.1038/emm.2016.6]
[3]
Pagliuca FW, Millman JR, Gürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell 2014; 159(2): 428-39.
[http://dx.doi.org/10.1016/j.cell.2014.09.040] [PMID: 25303535]
[4]
D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 2005; 23(12): 1534-41.
[http://dx.doi.org/10.1038/nbt1163] [PMID: 16258519]
[5]
D’Amour KA, Bang AG, Eliazer S, et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006; 24(11): 1392-401.
[http://dx.doi.org/10.1038/nbt1259] [PMID: 17053790]
[6]
Mfopou JK, Chen B, Mateizel I, Sermon K, Bouwens L. Noggin, retinoids, and fibroblast growth factor regulate hepatic or pancreatic fate of human embryonic stem cells. Gastroenterology 2010; 138(7): 2233-45.
[http://dx.doi.org/10.1053/j.gastro.2010.02.056] [PMID: 20206178]
[7]
Chen S, Borowiak M, Fox JL, et al. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 2009; 5(4): 258-65.
[http://dx.doi.org/10.1038/nchembio.154] [PMID: 19287398]
[8]
Nostro MC, Sarangi F, Yang C, et al. Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines. Stem Cell Reports 2015; 4(4): 591-604.
[http://dx.doi.org/10.1016/j.stemcr.2015.02.017] [PMID: 25843049]
[9]
Russ HA, Parent AV, Ringler JJ, et al. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J 2015; 34(13): 1759-72.
[http://dx.doi.org/10.15252/embj.201591058] [PMID: 25908839]
[10]
Sambathkumar R, Migliorini A, Nostro MC. Pluripotent stem cell-derived pancreatic progenitors and β-like cells for type 1 diabetes treatment. Physiology (Bethesda) 2018; 33(6): 394-402.
[http://dx.doi.org/10.1152/physiol.00026.2018] [PMID: 30303772]
[11]
Jennings RE, Berry AA, Strutt JP, Gerrard DT, Hanley NA. Human pancreas development. Development 2015; 142(18): 3126-37.http://dev.biologists.org/cgi/doi/10.1242/dev.120063 [Internet].
[http://dx.doi.org/doi.org/10.1242/dev.120063] [PMID: 26395141]
[12]
Li K, Zhu S, Russ HA, et al. Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages. Cell Stem Cell 2014; 14(2): 228-36.
[http://dx.doi.org/10.1016/j.stem.2014.01.006] [PMID: 24506886]
[13]
Rezania A, Bruin JE, Arora P, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 2014; 32(11): 1121-33.
[http://dx.doi.org/10.1038/nbt.3033] [PMID: 25211370]
[14]
Khan A, Kin T, Lei J, Linetsky E, Liu C, Luo X, et al. Functional assessment of purified human pancreatic islets: Glucose stimulated insulin release by ELISA - A standard operating procedure of the NIH clinical islet transplantation consortium. CellR4 2014; 2(2): e900.
[15]
Blum B, Hrvatin S, Schuetz C, Bonal C, Rezania A, Melton DA. Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3. Nat Biotechnol 2012; 30(3): 261-4.
[http://dx.doi.org/10.1038/nbt.2141] [PMID: 22371083]
[16]
Schroeder IS, Rolletschek A, Blyszczuk P, Kania G, Wobus AM. Differentiation of mouse embryonic stem cells to insulin-producing cells. Nat Protoc 2006; 1(2): 495-507.
[http://dx.doi.org/10.1038/nprot.2006.71] [PMID: 17406275]
[17]
Vethe H, Ghila L, Berle M, et al. The effect of WnT pathway modulators on human iPSC-derived pancreatic beta cell maturation. Front Endocrinol (Lausanne) 2019; 10(MAY): 293.
[http://dx.doi.org/10.3389/fendo.2019.00293] [PMID: 31139151]
[18]
Velazco-Cruz L, Song J, Maxwell KG, et al. Acquisition of dynamic function in human stem cell-derived β cells. Stem Cell Reports 2019; 12(2): 351-65.
[http://dx.doi.org/10.1016/j.stemcr.2018.12.012] [PMID: 30661993]
[19]
Nair GG, Liu JS, Russ HA, et al. Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells. Nat Cell Biol 2019; 21(2): 263-74.
[http://dx.doi.org/10.1038/s41556-018-0271-4] [PMID: 30710150]
[20]
Bi H, Ye K, Jin S. Proteomic analysis of decellularized pancreatic matrix identifies collagen V as a critical regulator for islet organogenesis from human pluripotent stem cells. Biomaterials 2020; 233.
[http://dx.doi.org/10.1016/j.biomaterials.2019.119673]
[21]
Hogrebe NJ, Augsornworawat P, Maxwell KG, Velazco-Cruz L, Millman JR. Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells. Nat Biotechnol 2020; 38(4): 460-70.
[http://dx.doi.org/10.1038/s41587-020-0430-6] [PMID: 32094658]
[22]
Coppieters KT, Wiberg A, Amirian N, Kay TW, von Herrath MG. Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals. Diabetes Metab Res Rev 2011; 27(8): 746-54.http://libweb.anglia.ac.uk.
[http://dx.doi.org/10.1002/dmrr.124] [PMID: 22069254]
[23]
Andrali SS, Sampley ML, Vanderford NL, Özcan S. Glucose regulation of insulin gene expression in pancreatic β-cells. Biochem J 2008; 415(1): 1-10.
[http://dx.doi.org/10.1042/BJ20081029] [PMID: 18778246]
[24]
Fu Z, Gilbert ER, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 2013; 9(1): 25-53.http://www.ncbi.nlm.nih.gov/pubmed/22974359%0Ahttp://www, pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3934755
[http://dx.doi.org/10.2174/157339913804143225] [PMID: 22974359]
[25]
MacDonald PE, Joseph JW, Rorsman P. Glucose-sensing mechanisms in pancreatic β-cells. Philos Trans R Soc Lond B Biol Sci 2005; 360(1464): 2211-25.
[http://dx.doi.org/10.1098/rstb.2005.1762] [PMID: 16321791]
[26]
Tu J, Tuch BE. Glucose regulates the maximal velocities of glucokinase and glucose utilization in the immature fetal rat pancreatic islet. Diabetes 1996; 45(8): 1068-75.
[http://dx.doi.org/10.2337/diab.45.8.1068] [PMID: 8690154]
[27]
Aguayo-Mazzucato C, Koh A, El Khattabi I, et al. Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia 2011; 54(3): 583-93.
[http://dx.doi.org/10.1007/s00125-010-2026-z] [PMID: 21190012]
[28]
Tan C, Tuch BE, Tu J, Brown SA. Role of NADH shuttles in glucose-induced insulin secretion from fetal beta-cells. Diabetes 2002; 51: 2989-96.
[29]
Bordone L, Motta MC, Picard F, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells. PLoS Biol 2006; 4(2)e31
[http://dx.doi.org/10.1371/journal.pbio.0040031] [PMID: 16366736]
[30]
Luu L, Dai FF, Prentice KJ, et al. The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing. Diabetologia 2013; 56(9): 2010-20.
[http://dx.doi.org/10.1007/s00125-013-2946-5] [PMID: 23783352]
[31]
Pinho AV, Bensellam M, Wauters E, et al. Pancreas-specific Sirt1-deficiency in mice compromises beta-cell function without development of hyperglycemia. PLoS One 2015; 10(6)e0128012
[http://dx.doi.org/10.1371/journal.pone.0128012] [PMID: 26046931]
[32]
Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005; 2(2): 105-17.
[http://dx.doi.org/10.1016/j.cmet.2005.07.001] [PMID: 16098828]
[33]
Michan S, Sinclair D. Sirtuins in mammals: Insights into their biological function. Biochem J 2007; 404(1): 1-13.http://www.biochemj.org/cgi/doi/10.1042/BJ20070140
[http://dx.doi.org/10.1042/BJ20070140] [PMID: 17447894]
[34]
Pezzolla D, López-Beas J, Lachaud CC, et al. Resveratrol ameliorates the maturation process of β-cell-like cells obtained from an optimized differentiation protocol of human embryonic stem cells. PLoS One 2015; 10(3)e0119904
[http://dx.doi.org/10.1371/journal.pone.0119904] [PMID: 25774684]
[35]
Chang Hung-Chun L. Guarente. SIRT1 and other sirtuins in Metabolism. Trends Endocrinol Metab 2014; 25(3): 138-45.
[36]
Haigis MC, Guarente LP. Mammalian sirtuins-emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006; 20(21): 2913-21.
[http://dx.doi.org/10.1101/gad.1467506] [PMID: 17079682]

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