Skip to main content
SpringerLink
Log in

Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Diabetes mellitus is the most prevailing disease with progressive incidence worldwide. To date, the pathogenesis of diabetes is far to be understood, and there is no permanent treatment available for diabetes. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs). ESCs and iPSCs have a great potential to differentiate into all cell types, and they have a high ability to differentiate into insulin-secreting β cells. Obtaining PSCs genetically identical to the patient presenting with diabetes has been a longstanding dream for the in vitro modeling of disease and ultimately cell therapy. For several years, somatic cell nuclear transfer (SCNT) was the method of choice to generate patient-specific ESC lines. However, this technology faces ethical and practical concerns. Interestingly, the recently established iPSC technology overcomes the major problems of other stem cell types including the lack of ethical concern and no risk of immune rejection. Several iPSC lines have been recently generated from patients with different types of diabetes, and most of these cell lines are able to differentiate into insulin-secreting β cells. In this review, we summarize recent advances in the differentiation of pancreatic β cells from PSCs, and describe the challenges for their clinical use in diabetes cell therapy. Furthermore, we discuss the potential use of patient-specific PSCs as an in vitro model, providing new insights into the pathophysiology of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Thomson, J. A., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.

    Article  CAS  PubMed  Google Scholar 

  3. Aoi, T., et al. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321(5889), 699–702.

    Article  CAS  PubMed  Google Scholar 

  4. Hanna, J., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133(2), 250–264.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Yu, J., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

    Article  CAS  PubMed  Google Scholar 

  6. Abdelalim, E. M. (2013). Molecular mechanisms controlling the cell cycle in embryonic stem cells. Stem Cell Reviews, 9(6), 764–773.

    Article  CAS  PubMed  Google Scholar 

  7. Ruiz, S., et al. (2011). A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Current Biology, 21(1), 45–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Zhang, Z. N., et al. (2013). Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53 through Sirt1-mediated deacetylation. Stem Cells, 32, 157–65.

    Article  CAS  Google Scholar 

  9. Chin, M. H., et al. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell, 5(1), 111–123.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Stadtfeld, M., et al. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Danaei, G., et al. (2011). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet, 378(9785), 31–40.

    Article  CAS  PubMed  Google Scholar 

  12. Gregg, E. W., et al. (2007). Mortality trends in men and women with diabetes, 1971 to 2000. Annals of Internal Medicine, 147(3), 149–155.

    Article  PubMed  Google Scholar 

  13. Tisch, R., & McDevitt, H. (1996). Insulin-dependent diabetes mellitus. Cell, 85(3), 291–297.

    Article  CAS  PubMed  Google Scholar 

  14. van Belle, T. L., Coppieters, K. T., & von Herrath, M. G. (2011). Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiological Reviews, 91(1), 79–118.

    Article  PubMed  CAS  Google Scholar 

  15. Doria, A., Patti, M. E., & Kahn, C. R. (2008). The emerging genetic architecture of type 2 diabetes. Cell Metabolism, 8(3), 186–200.

    Article  CAS  PubMed  Google Scholar 

  16. Bonnefond, A., Froguel, P., & Vaxillaire, M. (2010). The emerging genetics of type 2 diabetes. Trends in Molecular Medicine, 16(9), 407–416.

    Article  CAS  PubMed  Google Scholar 

  17. Vaxillaire, M., & Froguel, P. (2008). Monogenic diabetes in the young, pharmacogenetics and relevance to multifactorial forms of type 2 diabetes. Endocrine Reviews, 29(3), 254–264.

    Article  CAS  PubMed  Google Scholar 

  18. Bonnefond, A., et al. (2012). Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One, 7(6), e37423.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Efrat, S. (2008). Beta-cell replacement for insulin-dependent diabetes mellitus. Advanced Drug Delivery Reviews, 60(2), 114–123.

    Article  CAS  PubMed  Google Scholar 

  20. Maehr, R., et al. (2009). Generation of pluripotent stem cells from patients with type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15768–15773.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Tateishi, K., et al. (2008). Generation of insulin-secreting islet-like clusters from human skin fibroblasts. Journal of Biological Chemistry, 283(46), 31601–31607.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang, D., et al. (2009). Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Research, 19(4), 429–438.

    Article  CAS  PubMed  Google Scholar 

  23. Jiang, J., et al. (2007). Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells, 25(8), 1940–1953.

    Article  CAS  PubMed  Google Scholar 

  24. Chen, S., et al. (2009). A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nature Chemical Biology, 5(4), 258–265.

    Article  CAS  PubMed  Google Scholar 

  25. Kroon, E., et al. (2008). Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature Biotechnology, 26(4), 443–452.

    Article  CAS  PubMed  Google Scholar 

  26. D’Amour, K. A., et al. (2006). Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nature Biotechnology, 24(11), 1392–1401.

    Article  PubMed  CAS  Google Scholar 

  27. Lumelsky, N., et al. (2001). Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 292(5520), 1389–1394.

    Article  CAS  PubMed  Google Scholar 

  28. Thatava, T., et al. (2011). Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny. Gene Therapy, 18(3), 283–293.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Kunisada, Y., et al. (2012). Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. Stem Cell Research, 8(2), 274–284.

    Article  CAS  PubMed  Google Scholar 

  30. Nostro, M. C., et al. (2011). Stage-specific signaling through TGFbeta family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development, 138(5), 861–871.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Shim, J. H., et al. (2007). Directed differentiation of human embryonic stem cells towards a pancreatic cell fate. Diabetologia, 50(6), 1228–1238.

    Article  CAS  PubMed  Google Scholar 

  32. Gage, B. K., Webber, T. D., & Kieffer, T. J. (2013). Initial cell seeding density influences pancreatic endocrine development during in vitro differentiation of human embryonic stem cells. PLoS One, 8(12), e82076.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Jiang, W., et al. (2007). In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Research, 17(4), 333–344.

    Article  CAS  PubMed  Google Scholar 

  34. D’Amour, K. A., et al. (2005). Efficient differentiation of human embryonic stem cells to definitive endoderm. Nature Biotechnology, 23(12), 1534–1541.

    Article  PubMed  CAS  Google Scholar 

  35. Mfopou, J. K., et al. (2010). Noggin, retinoids, and fibroblast growth factor regulate hepatic or pancreatic fate of human embryonic stem cells. Gastroenterology, 138(7), 2233–2245. 2245 e1–14.

    Article  CAS  PubMed  Google Scholar 

  36. Johannesson, M., et al. (2009). FGF4 and retinoic acid direct differentiation of hESCs into PDX1-expressing foregut endoderm in a time- and concentration-dependent manner. PLoS One, 4(3), e4794.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. McLean, A. B., et al. (2007). Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells, 25(1), 29–38.

    Article  CAS  PubMed  Google Scholar 

  38. Tian, T., & Meng, A. M. (2006). Nodal signals pattern vertebrate embryos. Cellular and Molecular Life Sciences, 63(6), 672–685.

    Article  CAS  PubMed  Google Scholar 

  39. Kubo, A., et al. (2004). Development of definitive endoderm from embryonic stem cells in culture. Development, 131(7), 1651–1662.

    Article  CAS  PubMed  Google Scholar 

  40. Hosoya, M. (2012). Preparation of pancreatic beta-cells from human iPS cells with small molecules. Islets, 4(3), 249–252.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Bruin, J. E., et al. (2013). Characterization of polyhormonal insulin-producing cells derived in vitro from human embryonic stem cells. Stem Cell Research, 12(1), 194–208.

    Article  PubMed  CAS  Google Scholar 

  42. Bone, H. K., et al. (2011). A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3. Journal of Cell Science, 124(Pt 12), 1992–2000.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Borowiak, M., et al. (2009). Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell Stem Cell, 4(4), 348–358.

    Article  CAS  PubMed  Google Scholar 

  44. Wandzioch, E., & Zaret, K. S. (2009). Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science, 324(5935), 1707–1710.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Bernardo, A. S., et al. (2009). Biphasic induction of Pdx1 in mouse and human embryonic stem cells can mimic development of pancreatic beta-cells. Stem Cells, 27(2), 341–351.

    Article  CAS  PubMed  Google Scholar 

  46. Zhu, F. F., et al. (2011). Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells. Diabetologia, 54(9), 2325–2336.

    Article  CAS  PubMed  Google Scholar 

  47. Sakano, D., et al. (2014). VMAT2 identified as a regulator of late-stage beta-cell differentiation. Nat Chem Biol, 10, 141–8.

    Article  CAS  PubMed  Google Scholar 

  48. Ohmine, S., et al. (2012). Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. Aging (Albany NY), 4(1), 60–73.

    CAS  Google Scholar 

  49. Rezania, A., et al. (2013). Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. Stem Cells, 31, 2432–2442.

    Article  CAS  PubMed  Google Scholar 

  50. Blyszczuk, P., et al. (2003). Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proceedings of the National Academy of Sciences of the United States of America, 100(3), 998–1003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Kwon, Y. D., et al. (2005). Cellular manipulation of human embryonic stem cells by TAT-PDX1 protein transduction. Molecular Therapy, 12(1), 28–32.

    Article  CAS  PubMed  Google Scholar 

  52. Soria, B., et al. (2000). Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes, 49(2), 157–162.

    Article  CAS  PubMed  Google Scholar 

  53. Liew, C. G., et al. (2008). PAX4 enhances beta-cell differentiation of human embryonic stem cells. PLoS One, 3(3), e1783.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Hua, H., et al. (2013). iPSC-derived beta cells model diabetes due to glucokinase deficiency. Journal of Clinical Investigation, 123(7), 3146–3153.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Thatava, T., et al. (2013). Intrapatient variations in type 1 diabetes-specific iPS cell differentiation into insulin-producing cells. Molecular Therapy, 21(1), 228–239.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Teo, A. K., Wagers, A. J., & Kulkarni, R. N. (2013). New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metabolism, 18(6), 775–791.

    Article  CAS  PubMed  Google Scholar 

  57. Kelly, O. G., et al. (2011). Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nature Biotechnology, 29(8), 750–756.

    Article  CAS  PubMed  Google Scholar 

  58. Cai, J., et al. (2010). Generation of homogeneous PDX1(+) pancreatic progenitors from human ES cell-derived endoderm cells. Journal of Molecular Cell Biology, 2(1), 50–60.

    Article  CAS  PubMed  Google Scholar 

  59. Xu, X., Browning, V. L., & Odorico, J. S. (2011). Activin, BMP and FGF pathways cooperate to promote endoderm and pancreatic lineage cell differentiation from human embryonic stem cells. Mechanisms of Development, 128(7–10), 412–427.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Rezania, A., et al. (2012). Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes, 61(8), 2016–2029.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Bruin, J. E., et al. (2013). Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice. Diabetologia, 56(9), 1987–1998.

    Article  PubMed  Google Scholar 

  62. Alipio, Z., et al. (2010). Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proceedings of the National Academy of Sciences of the United States of America, 107(30), 13426–13431.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Jeon, K., et al. (2012). Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model. Stem Cells and Development, 21(14), 2642–2655.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Yang, X., et al. (2007). Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nature Genetics, 39(3), 295–302.

    Article  CAS  PubMed  Google Scholar 

  65. Lanza, R. P., Cibelli, J. B., & West, M. D. (1999). Prospects for the use of nuclear transfer in human transplantation. Nature Biotechnology, 17(12), 1171–1174.

    Article  CAS  PubMed  Google Scholar 

  66. Wilmut, I., et al. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385(6619), 810–813.

    Article  CAS  PubMed  Google Scholar 

  67. Tachibana, M., et al. (2013). Human embryonic stem cells derived by somatic cell nuclear transfer. Cell, 153(6), 1228–1238.

    Article  CAS  PubMed  Google Scholar 

  68. Araki, R., et al. (2013). Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature, 494(7435), 100–104.

    Article  CAS  PubMed  Google Scholar 

  69. Sermon, K. D., et al. (2009). Creation of a registry for human embryonic stem cells carrying an inherited defect: joint collaboration between ESHRE and hESCreg. Human Reproduction, 24(7), 1556–1560.

    Article  CAS  PubMed  Google Scholar 

  70. Verlinsky, Y., et al. (2005). Human embryonic stem cell lines with genetic disorders. Reproductive Biomedicine Online, 10(1), 105–110.

    Article  CAS  PubMed  Google Scholar 

  71. Eiges, R., et al. (2007). Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell, 1(5), 568–577.

    Article  CAS  PubMed  Google Scholar 

  72. Mateizel, I., et al. (2006). Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders. Human Reproduction, 21(2), 503–511.

    Article  CAS  PubMed  Google Scholar 

  73. Lee, G., & Studer, L. (2010). Induced pluripotent stem cell technology for the study of human disease. Nature Methods, 7(1), 25–27.

    Article  CAS  PubMed  Google Scholar 

  74. Maehr, R. (2011). iPS cells in type 1 diabetes research and treatment. Clinical Pharmacology and Therapeutics, 89(5), 750–753.

    Article  CAS  PubMed  Google Scholar 

  75. Teo, A. K., et al. (2013). Derivation of human induced pluripotent stem cells from patients with maturity onset diabetes of the young. Journal of Biological Chemistry, 288(8), 5353–5356.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Kudva, Y. C., et al. (2012). Transgene-free disease-specific induced pluripotent stem cells from patients with type 1 and type 2 diabetes. Stem Cells Translational Medicine, 1(6), 451–461.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Velho, G., et al. (1992). Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young. Lancet, 340(8817), 444–448.

    Article  CAS  PubMed  Google Scholar 

  78. Estalella, I., et al. (2007). Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. Clinical Endocrinology, 67(4), 538–546.

    CAS  PubMed  Google Scholar 

  79. Froguel, P., et al. (1993). Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. New England Journal of Medicine, 328(10), 697–702.

    Article  CAS  PubMed  Google Scholar 

  80. Byrne, M. M., et al. (1994). Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. Journal of Clinical Investigation, 93(3), 1120–1130.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Li, H., et al. (2009). The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature, 460(7259), 1136–1139.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Banito, A., et al. (2009). Senescence impairs successful reprogramming to pluripotent stem cells. Genes and Development, 23(18), 2134–2139.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Hanna, J., et al. (2009). Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell, 4(6), 513–524.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.

    Article  CAS  PubMed  Google Scholar 

  85. Okita, K., et al. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903), 949–953.

    Article  CAS  PubMed  Google Scholar 

  86. Soldner, F., et al. (2009). Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5), 964–977.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Kaji, K., et al. (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458(7239), 771–775.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Woltjen, K., et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458(7239), 766–770.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Zhou, H., et al. (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 4(5), 381–384.

    Article  CAS  PubMed  Google Scholar 

  90. Kim, D., et al. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4(6), 472–476.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Yamanaka, S. (2007). Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell, 1(1), 39–49.

    Article  CAS  PubMed  Google Scholar 

  92. Knoepfler, P. S. (2008). Why myc? An unexpected ingredient in the stem cell cocktail. Cell Stem Cell, 2(1), 18–21.

    Article  CAS  PubMed  Google Scholar 

  93. Nakagawa, M., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 26(1), 101–106.

    Article  CAS  PubMed  Google Scholar 

  94. Wernig, M., et al. (2008). c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell, 2(1), 10–12.

    Article  CAS  PubMed  Google Scholar 

  95. Obokata, H., et al. (2014). Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature, 505(7485), 641–647.

    Article  CAS  PubMed  Google Scholar 

  96. Obokata, H., et al. (2014). Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature, 505(7485), 676–680.

    Article  CAS  PubMed  Google Scholar 

  97. Santana, A., et al. (2006). Insulin-producing cells derived from stem cells: recent progress and future directions. Journal of Cellular and Molecular Medicine, 10(4), 866–883.

    Article  CAS  PubMed  Google Scholar 

  98. Shapiro, A. M., et al. (2000). Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New England Journal of Medicine, 343(4), 230–238.

    Article  CAS  PubMed  Google Scholar 

  99. Penfornis, A., & Kury-Paulin, S. (2006). Immunosuppressive drug-induced diabetes. Diabetes & Metabolism, 32(5 Pt 2), 539–546.

    Article  CAS  Google Scholar 

  100. Fiorina, P., Voltarelli, J., & Zavazava, N. (2011). Immunological applications of stem cells in type 1 diabetes. Endocrine Reviews, 32(6), 725–754.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Patterson, M., et al. (2012). Defining the nature of human pluripotent stem cell progeny. Cell Research, 22(1), 178–193.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of Interest Statement

We declare no potential conflicts of interest

Author information

Authors and Affiliations

  1. Qatar Biomedical Research Institute, Qatar Foundation, Education City, 5825, Doha, Qatar

    Essam M. Abdelalim, Amélie Bonnefond & Philippe Froguel

  2. Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt

    Essam M. Abdelalim

  3. CNRS UMR8199, Pasteur Institute of Lille, Lille, France

    Amélie Bonnefond & Philippe Froguel

  4. Lille 2 University, Lille, France

    Amélie Bonnefond & Philippe Froguel

  5. European Genomic Institute for Diabetes (EGID), Lille, France

    Amélie Bonnefond & Philippe Froguel

  6. INSERM UMR S935, ESTeam Paris Sud, Université Paris Sud 11, Villejuif, France

    Annelise Bennaceur-Griscelli

  7. AP-HP Laboratory of Hematology, CHU, Bicêtre, France

    Annelise Bennaceur-Griscelli

  8. Department of Genomics of Common Disease, Hammersmith Hospital, Imperial College London, London, UK

    Philippe Froguel

Authors
  1. Essam M. Abdelalim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amélie Bonnefond
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annelise Bennaceur-Griscelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philippe Froguel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Essam M. Abdelalim or Philippe Froguel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdelalim, E.M., Bonnefond, A., Bennaceur-Griscelli, A. et al. Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes. Stem Cell Rev and Rep 10, 327–337 (2014). https://doi.org/10.1007/s12015-014-9503-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-014-9503-6

Keywords

Search

Navigation