Exp Clin Endocrinol Diabetes 2020; 128(05): 339-346
DOI: 10.1055/a-0661-5873
Mini-Review
© Georg Thieme Verlag KG Stuttgart · New York

Generation of Pancreatic β-cells From iPSCs and their Potential for Type 1 Diabetes Mellitus Replacement Therapy and Modelling

Maria Csobonyeiova
1   Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
,
Stefan Polak
1   Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
,
Lubos Danisovic
2   Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
3   REGENMED Ltd., Bratislava, Slovakia
› Author Affiliations
Further Information

Publication History

received 30 April 2018
revised  16 July 2018

accepted 19 July 2018

Publication Date:
16 August 2018 (online)

Abstract

Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting β-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic β-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease. Therefore, much effort has focused on understanding the regulation of β-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source for T1D modelling and cell replacement therapy because of their ability to differentiate into all cell types in vitro. Recent advances in stem cell-based therapy and gene-editing tools have enabled the generation of functionally adult pancreatic β-cells derived from iPSCs. Although animal and human pancreatic development and β-cell physiology have significant differences, animal models represent an important tool in evaluating the therapeutic potential of iPSC-derived β-cells on type 1 diabetes treatment. This review outlines the recent progress in iPSC-derived β-cell differentiation methods, disease modelling, and future perspectives.

 
  • References

  • 1 Maahs DM, West NA, Lawrence JM. et al. Chapter 1: Epidemiology of Type 1 Diabetes. Endocrinol Metab Clin North Am 2010; 39: 481-497
  • 2 Onengut-Gumuscu S, Chen WM, Burren O. et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet 2015; 47: 381-386
  • 3 Thakkar UG, Vanikar AV, Trivedi HL. Should we practice stem cell therapy for type 1 diabetes mellitus as precision medicine?. Cytotherapy 2017; 19: 574-576
  • 4 Kawser Hossain M, Abdal Dayem A, Han J. et al. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells. Int J Mol Sci 2016; 17: 256
  • 5 Nathan DM, Bayless M, Cleary P. et al. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Advances and Contributions. Diabetes 2013; 62: 3976-3986
  • 6 Shapiro AM. State of the art of clinical islet transplantation and novel protocols of immunosuppression. Curr Diabet Rep 2011; 11: 345-354
  • 7 Teramura Y, Iwata H. Bioartificial pancreas microencapsulation and conformal coating of islet of Langerhans. Adv Drug Deliv Rev 2010; 62: 827-840
  • 8 Cañibano-Hernández A, Sáenz Del Burgo L, Espona-Noguera A. et al. Current advanced therapy cell-based medicinal products for type-1-diabetes treatment. Int J Pharm 2018; 543: 107-112
  • 9 Sordi V, Pellegrini S, Krampera M. et al. Stem cells to restore insulin production and cure diabetes. Nutr Metab Cardiovasc Dis 2017; 27: 583-600
  • 10 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: 1392-1401
  • 11 Kroon E, Martinson LA, Kadoya K. et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26: 443-452
  • 12 Rezania A, Bruin JE, Riedel MJ. et al. Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice. Diabetes 2012; 61: 2016-2029
  • 13 Chmielowiec J, Borowiak M. In vitro differentiation and expansion of human pluripotent stem cell-derived pancreatic progenitors. Rev Diabet Stud 2014; 1: 19-34
  • 14 Bruin JE, Asadi A, Fox JK. et al. Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice. Stem Cell Reports 2015; 5: 1081-1096
  • 15 Balboa D, Otonkoski T. Human pluripotent stem cell based islet models for diabetes research. Best Pract Res Clin Endocrinol Metab 2015; 29: 899-909
  • 16 Lu J, Xia Q, Zhou Q. How to make insulin-producing pancreatic β cells for diabetes treatment. Sci China Life Sci 2017; 60: 239-248
  • 17 McLean AB, D’Amour KA, Jones KL. et al. Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells 2007; 25: 29-38
  • 18 Chen AE, Borowiak M, Sherwood RI. et al. Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation. Development 2013; 140: 675-686
  • 19 Rezania A, Bruin JE, Xu J. et al. Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. Stem Cells 2013; 31: 2432-2442
  • 20 McGaugh EC, Nostro MC. Efficient Differentiation of Pluripotent Stem Cells to NKX6-1 + Pancreatic Progenitors. J Vis Exp 2017
  • 21 Bar-Nur O, Russ HA, Efrat S. et al. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 2011; 9: 17-23
  • 22 Zhang D, Jiang W, Liu M. et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 2009; 19: 429-438
  • 23 Thatava T, Kudva YC, Edukulla R. et al. Intrapatient variations in type 1 diabetes specific iPS cell differentiation into insulin-producing cells. Mol Ther 2013; 21: 228-239
  • 24 Quiskamp N, Bruin JE, Kieffer TJ. Differentiation of human pluripotent stem cells into β-cells: Potential and challenges. Best Pract Res Clin Endocrinol Metab 2015; 29: 833-847
  • 25 Tateishi K, He J, Taranova O. et al. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 2008; 283: 31601-31617
  • 26 Alipio Z, Liao W, Roemer EJ. et al. Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci U S A 2010; 107: 13426-13431
  • 27 Maehr R, Chen S, Snitow M. et al. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci U S A 2009; 106: 15768-15773
  • 28 Jeon K, Lim H, Kim JH. et al. Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model. Stem Cells Dev 2012; 21: 2642-2655
  • 29 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: 1121-1133
  • 30 Pagliuca FW, Millman JR, Gürtler M. et al. Generation of functional human pancreatic β cells in vitro. Cell 2014; 159: 428-439
  • 31 Rajaei B, Shamsara M, Amirabad LM. et al. Pancreatic Endoderm-Derived From Diabetic Patient-Specific Induced Pluripotent Stem Cell Generates Glucose-Responsive Insulin-Secreting Cells. J Cell Physiol 2017; 232: 2616-2625
  • 32 Shaer A, Azarpira N, Karimi MH. Differentiation of Human Induced Pluripotent Stem Cells into Insulin-Like Cell Clusters with miR-186 and miR-375 by using chemical transfection. Appl Biochem Biotechnol 2014; 174: 242-258
  • 33 Lahmy R, Soleimani M, Sanati MH. et al. MiRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells. Mol Biol Rep 2014; 41: 2055-2066
  • 34 Konagaya S, Iwata H. Reproducible preparation of spheroids of pancreatic hormone positive cells from human iPS cells: An in vitro study. Biochim Biophys Acta 2016; 1860: 2008-2016
  • 35 Hirano K, Konagaya S, Turner A. et al. Closed-channel culture system for efficient and reproducible differentiation of human pluripotent stem cells into islet cells. Biochem Biophys Res Commun 2017; 487: 344-350
  • 36 Manzar GS, Kim EM, Zavazava N. Demethylation of induced pluripotent stem cells from type 1 diabetic patients enhances differentiation into functional pancreatic β cells. J Biol Chem 2017; 292: 14066-14079
  • 37 Stepniewski J, Kachamakova-Trojanowska N, Ogrocki D. et al. Induced pluripotent stem cells as a model for diabetes investigation. Sci Rep 2015; 5: 8597
  • 38 Zhu FF, Zhang PB, Zhang DH. et al. Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells. Diabetologia 2011; 54: 2325-2336
  • 39 Iovino S, Burkart AM, Kriauciunas K. et al. Genetic Insulin Resistance Is a Potent Regulator of Gene Expression and Proliferation in Human iPS Cells. Diabetes 2014; 63: 4130-4142
  • 40 Burkart AM, Tan K, Warren L. et al. Insulin Resistance in Human iPS Cells Reduces Mitochondrial Size and Function. Sci Rep 2016; 6: 22788
  • 41 Huang Y, Wan J, Guo Y. et al. Transcriptome Analysis of Induced Pluripotent Stem Cell (iPSC)-derived Pancreatic β-like Cell Differentiation. Cell Transplant 2017; 26: 1380-1391
  • 42 Sordi V, Pellegrini S, Piemonti L. Immunological Issues After Stem Cell-Based β Cell Replacement. Curr Diab Rep 2017; 17: 68
  • 43 Araki R, Uda M, Hoki Y. et al. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 2013; 494: 100-104
  • 44 Zhao T, Zhang ZN, Rong Z. et al. Immunogenicity of induced pluripotent stem cells. Nature 2011; 474: 212-215
  • 45 Orive G, Emerich D, Khademhosseini A. et al. Engineering a Clinically Translatable Bioartificial Pancreas to Treat Type I Diabetes. Trends Biotechnol 2018; 36: 445-456
  • 46 Tomei AA, Villa C, Ricordi C. Development of an encapsulated stem cell-based therapy for diabetes. Expert Opin Biol Ther 2015; 15: 1321-1336
  • 47 Song S, Roy S. Progress and Challenges in Macroencapsulation Approaches for Type 1 Diabetes (T1D) Treatment: Cells, Biomaterials, and Devices. Biotechnol Bioeng. 2016; 113: 1381-1402
  • 48 Calafiore R, Basta G. Clinical application of microencapsulated islets: Actual prospectives on progress and challenges. Adv Drug Deliv Rev 2014; 67-68: 84
  • 49 Barkai U, Rotem A, de Vos P. Survival of encapsulated islets: More than a membrane story. World J Transplant 2016; 6: 69-90
  • 50 Kozlovskaya V, Zavgorodnya O, Chen Y. et al. Ultrathin polymeric coatings based on hydrogen-bonded polyphenol for protection of pancreatic islet cells. Adv Funct Mater 2012; 22: 3389-3398
  • 51 Korsgren O. Islet Encapsulation: Physiological Possibilities and Limitations. Diabetes 2017; 66: 1748-1754
  • 52 Bhujbal SV, de Haan B, Niclou SP et al. A novel multilayer immunoisolating encapsulation system overcoming protrusion of cells. Sci Rep 2014
  • 53 Bandiera A. Transglutaminase-catalyzed preparation of human elastin-like polypeptide-based three-dimensional matrices for cell encapsulation. Enzyme Microb Technol 2011; 49: 347-352
  • 54 Prochorov AV, Tretjak SI, Goranov VA. et al. Treatment of insulin dependent diabetes mellitus with intravascular transplantation of pancreatic islet cells without immunosuppressive therapy. Adv Med Sci 2008; 53: 240-244
  • 55 Chang R, Faleo G, Russ HA. et al. Nanoporous Immunoprotective Device for Stem-Cell-Derived β-Cell Replacement Therapy. ACS Nano 2017; 11: 7747-7757
  • 56 Carlsson PO, Espes D, Sedigh A. et al. Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus. Am J Transplant 2018; 18: 1735-1744
  • 57 Skrzypek K, Groot Nibbelink M, van Lente J. et al. Pancreatic islet macroencapsulation using microwell porous membranes. Sci Rep 2017; 7: 9186
  • 58 Jacobson EF, Tzanakakis ES. Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions. J Biomed Eng 2017; 11: 21
  • 59 Kawser Hossain M, Abdal Dayem A, Han J. et al. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells. Int J Mol Sci 2016; 17: 256
  • 60 Calafiore R, Basta G. Stem cells for the cell and molecular therapy of type 1 diabetes mellitus (T1D): The gap between dream and reality. Am J Stem Cells 2015; 4: 22-31
  • 61 Miura K, Okada Y, Aoi T. et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 2009; 27: 743-745
  • 62 Millman JR, Xie C, Van Dervort A. et al. Corrigendum: Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun 2016; 7: 12379
  • 63 Liu J, Joglekar MV, Sumer H. et al. Integration-Free Human Induced Pluripotent Stem Cells From Type 1 Diabetes Patient Skin Fibroblasts Show Increased Abundance of Pancreas-Specific microRNAs. Cell Med 2014; 7: 15-24