open access

Vol 57, No 3 (2019)
Review paper
Submitted: 2019-04-19
Accepted: 2019-08-06
Published online: 2019-08-09
Get Citation

Pancreatic β-cell replacement: advances in protocols used for differentiation of pancreatic progenitors to β-like cells

Muhammad Waseem Ghani1, Li Ye1, Zhao Yi1, Hammad Ghani2, Muhammad Waseem Birmani1, Aamir Nawab1, Lang Guan Cun1, Liu Bin1, Xiao Mei1
DOI: 10.5603/FHC.a2019.0013
Pubmed: 31396945
Folia Histochem Cytobiol 2019;57(3):101-115.
  1. Department of Livestock Production and Management, Agricultural College, Guangdong Ocean University, Zhanjiang, Guangdong, China, 524088, China
  2. Nawaz Sharif Medical College University of Gujrat, Punjab, Pakistan, Gujrat, Pakistan

open access

Vol 57, No 3 (2019)
Submitted: 2019-04-19
Accepted: 2019-08-06
Published online: 2019-08-09


Insulin-producing cells derived from in vitro differentiation of stem cells and non-stem cells by using different factors can spare the need for genetic manipulation and provide a cure for diabetes. In this context, pancreatic progenitors differentiating to β-like cells garner increasing attention as β-cell replacement source. This kind of cell therapy has the potential to cure diabetes, but is still on its way of being clinically useful. The primary restriction for in vitro production of mature and functional β-cells is developing a physiologically relevant in vitro culture system which can mimic in vivo pathways of islet development. In order to achieve this target, different approaches have been attempted for the differentiation of pancreatic stem/progenitor cells to β-like cells. Here, we will review some of the state-of-the-art protocols for the differentiation of pancreatic progenitors and differentiated pancreatic cells into β-like cells with a focus on pancreatic duct cells.


Insulin-producing cells derived from in vitro differentiation of stem cells and non-stem cells by using different factors can spare the need for genetic manipulation and provide a cure for diabetes. In this context, pancreatic progenitors differentiating to β-like cells garner increasing attention as β-cell replacement source. This kind of cell therapy has the potential to cure diabetes, but is still on its way of being clinically useful. The primary restriction for in vitro production of mature and functional β-cells is developing a physiologically relevant in vitro culture system which can mimic in vivo pathways of islet development. In order to achieve this target, different approaches have been attempted for the differentiation of pancreatic stem/progenitor cells to β-like cells. Here, we will review some of the state-of-the-art protocols for the differentiation of pancreatic progenitors and differentiated pancreatic cells into β-like cells with a focus on pancreatic duct cells.

Get Citation


β-cell replacement; transdifferentiation; pancreatic duct cells; acinar cells; centroacinar cells; endocrine cells; mesenchymal stem cells; β-like cells

About this article

Pancreatic β-cell replacement: advances in protocols used for differentiation of pancreatic progenitors to β-like cells


Folia Histochemica et Cytobiologica


Vol 57, No 3 (2019)

Article type

Review paper



Published online






Bibliographic record

Folia Histochem Cytobiol 2019;57(3):101-115.


β-cell replacement
pancreatic duct cells
acinar cells
centroacinar cells
endocrine cells
mesenchymal stem cells
β-like cells


Muhammad Waseem Ghani
Li Ye
Zhao Yi
Hammad Ghani
Muhammad Waseem Birmani
Aamir Nawab
Lang Guan Cun
Liu Bin
Xiao Mei

References (119)
  1. International Diabetes Federation. IDF 2017. WwwDiabetesatlasOrg. 2017;8:1–2.
  2. Zimmet P, Alberti KG, Magliano DJ, et al. Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat Rev Endocrinol. 2016; 12(10): 616–622.
  3. Afelik S, Rovira M, Afelik S, et al. Pancreatic β-cell regeneration: advances in understanding the genes and signaling pathways involved. Genome Med. 2017; 9(1): 42.
  4. Jacobson EF, Tzanakakis ES. Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions. J Biol Eng. 2017; 11: 21.
  5. Cañibano-Hernández A, Saenz Del Burgo L, Espona-Noguera A, et al. Hyaluronic Acid Promotes Differentiation of Mesenchymal Stem Cells from Different Sources toward Pancreatic Progenitors within Three-Dimensional Alginate Matrixes. Mol Pharm. 2019; 16(2): 834–845.
  6. Peng BY, Dubey NK, Mishra VK, et al. Addressing Stem Cell Therapeutic Approaches in Pathobiology of Diabetes and Its Complications. J Diabetes Res. 2018; 2018: 7806435.
  7. Zhou Q, Melton D. Pancreas regeneration. Nature. 2018; 557(7705): 351–358.
  8. Qadir MM, Álvarez-Cubela S, Klein D, et al. P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics. Cell Rep. 2018; 22(9): 2408–2420.
  9. Alberts B. Secialized Tissues, Stem Cells, and Tissue Renewal. In: Molecular Biology of The Cell 5th Edition. 2008 p : 1417–86.
  10. Afelik S, Rovira M. Pancreatic β-cell regeneration: Facultative or dedicated progenitors? Mol Cell Endocrinol. 2017; 445: 85–94.
  11. Tata PR, Mou H, Pardo-Saganta A, et al. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature. 2013; 503(7475): 218–223.
  12. Slack JM, Tosh D. Transdifferentiation and metaplasia--switching cell types. Curr Opin Genet Dev. 2001; 11(5): 581–586.
  13. Storz P. Acinar cell plasticity and development of pancreatic ductal adenocarcinoma. Nat Rev Gastroenterol Hepatol. 2017; 14(5): 296–304.
  14. Puri S, Hebrok M. Cellular plasticity within the pancreas--lessons learned from development. Dev Cell. 2010; 18(3): 342–356.
  15. Migliorini A, Bader E, Lickert H. Islet cell plasticity and regeneration. Mol Metab. 2014; 3(3): 268–274.
  16. Dor Y, Brown J, Martinez OI, et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 2004; 429(6987): 41–46.
  17. Domínguez-Bendala J, Qadir MM, Pastori RL. Pancreatic Progenitors: There and Back Again. Trends Endocrinol Metab. 2019; 30(1): 4–11.
  18. van der Meulen T, Mawla AM, DiGruccio MR, et al. Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets. Cell Metab. 2017; 25(4): 911–926.e6.
  19. Talchai C, Xuan S, Lin HV, et al. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 2012; 150(6): 1223–1234.
  20. Tan J, Liu L, Li B, et al. Pancreatic stem cells differentiate into insulin-secreting cells on fibroblast-modified PLGA membranes. Mater Sci Eng C Mater Biol Appl. 2019; 97: 593–601.
  21. Klein D, Álvarez-Cubela S, Lanzoni G, et al. BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion. Diabetes. 2015; 64(12): 4123–4134.
  22. Delaspre F, Beer RL, Rovira M, et al. Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration. Diabetes. 2015; 64(10): 3499–3509.
  23. Dhawan S, Dirice E, Kulkarni RN, et al. Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication. Diabetes. 2016; 65(5): 1208–1218.
  24. Andrzejewski D, Brown ML, Ungerleider N, et al. Activins A and B Regulate Fate-Determining Gene Expression in Islet Cell Lines and Islet Cells From Male Mice. Endocrinology. 2015; 156(7): 2440–2450.
  25. Chera S, Baronnier D, Ghila L, et al. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers. Nature. 2014; 514(7523): 503–507.
  26. Duruksu G, Aciksari A. Guiding the Differentiation Direction of Pancreatic Islet-Derived Stem Cells by Glycated Collagen. Stem Cells Int. 2018; 2018: 6143081.
  27. Balboa D, Saarimäki-Vire J, Otonkoski T. Concise Review: Human Pluripotent Stem Cells for the Modeling of Pancreatic β-Cell Pathology. Stem Cells. 2019; 37(1): 33–41.
  28. Pagliuca FW, Millman JR, Gürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014; 159(2): 428–439.
  29. Pokrywczynska M, Lanzoni G, Ricordi C, et al. From Adult Pancreatic Islets to Stem Cells. In: Atala A (eds). Principles of Regenerative Medicine. 3rd ed. , Academic Press. ; 2018.
  30. Avolio F, Pfeifer A, Courtney M, et al. From pancreas morphogenesis to β-cell regeneration. Curr Top Dev Biol. 2013; 106: 217–238.
  31. Xu X, Bonne S, Leu N De, Xiao X, Hoker JD, Stange G, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell [Internet]. 2008;132(2):197–207. Available from:
  32. Inada A, Nienaber C, Katsuta H, et al. Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc Natl Acad Sci U S A. 2008; 105(50): 19915–19919.
  33. Li WC, Rukstalis JM, Nishimura W, et al. Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats. J Cell Sci. 2010; 123(Pt 16): 2792–2802.
  34. Pierreux CE, Poll AV, Kemp CR, et al. The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse. Gastroenterology. 2006; 130(2): 532–541.
  35. Zhang H, Ables ET, Pope CF, et al. Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal differentiation. Mech Dev. 2009; 126(11-12): 958–973.
  36. Seymour PA, Freude KK, Tran MN, et al. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A. 2007; 104(6): 1865–1870.
  37. Maestro MA, Boj SF, Luco RF, et al. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet. 2003; 12(24): 3307–3314.
  38. Christensen AA, Gannon M. The Beta Cell in Type 2 Diabetes. Curr Diab Rep. 2019; 19(9): 81.
  39. El-Gohary Y, Wiersch J, Tulachan S, et al. Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells. Endocrinology. 2016; 157(1): 166–175.
  40. Criscimanna A, Speicher JA, Houshmand G, et al. Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice. Gastroenterology. 2011; 141(4): 1451–62, 1462.e1.
  41. Skurikhin EG, Ermakova NN, Khmelevskaya ES, et al. Differentiation of pancreatic stem and progenitor β-cells into insulin secreting cells in mice with diabetes mellitus. Bull Exp Biol Med. 2014; 156(6): 726–730.
  42. Zhang M, Lin Q, Qi T, et al. Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes. Proc Natl Acad Sci U S A. 2016; 113(3): 650–655.
  43. Shaotang Y, Yuxian Y, Jiang W, et al. Multipotent of Monoclonal Epithelial Stem Cells Derived from Pancreatic Duct. Chinese J Cell Biol. 2018; 40(1): 41–6.
  44. Gagliardino JJ, Del Zotto H, Massa L, et al. Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors. J Endocrinol. 2003; 177(2): 249–259.
  45. Sugimoto H, LeBleu VS, Bosukonda D, et al. Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis. Nat Med. 2012; 18(3): 396–404.
  46. Suarez-Pinzon WL, Yan Y, Power R, et al. Combination therapy with epidermal growth factor and gastrin increases beta-cell mass and reverses hyperglycemia in diabetic NOD mice. Diabetes. 2005; 54(9): 2596–2601.
  47. Ogawa N, List JF, Habener JF, et al. Cure of overt diabetes in NOD mice by transient treatment with anti-lymphocyte serum and exendin-4. Diabetes. 2004; 53(7): 1700–1705.
  48. Suarez-Pinzon WL, Lakey JRT, Brand SJ, et al. Combination therapy with epidermal growth factor and gastrin induces neogenesis of human islet {beta}-cells from pancreatic duct cells and an increase in functional {beta}-cell mass. J Clin Endocrinol Metab. 2005; 90(6): 3401–3409.
  49. Miettinen PJ, Huotari M, Koivisto T, et al. Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development. 2000; 127(12): 2617–2627.
  50. Corritore E, Lee YS, Sokal EM, et al. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells. Ther Adv Endocrinol Metab. 2016; 7(4): 182–199.
  51. Hui H, Wright C, Perfetti R. Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. Diabetes. 2001; 50(4): 785–796.
  52. Li Li, Lili R, Hui Qi, et al. Combination of GLP-1 and sodium butyrate promote differentiation of pancreatic progenitor cells into insulin-producing cells. Tissue Cell. 2008; 40(6): 437–445.
  53. Haumaitre C, Lenoir O, Scharfmann R. Histone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors. Mol Cell Biol. 2008; 28(20): 6373–6383.
  54. Chen XC, Liu H, Li H, et al. In vitro expansion and differentiation of rat pancreatic duct-derived stem cells into insulin secreting cells using a dynamicthree-dimensional cell culture system. Genet Mol Res. 2016; 15(2).
  55. Means AL, Meszoely IM, Suzuki K, et al. Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development. 2005; 132(16): 3767–3776.
  56. Pan FC, Bankaitis ED, Boyer D, et al. Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development. 2013; 140(4): 751–764.
  57. Baeyens L, Lemper M, Leuckx G, et al. Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. Nat Biotechnol. 2014; 32(1): 76–83.
  58. Clayton HW, Osipovich AB, Stancill JS, et al. Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming. Cell Rep. 2016; 17(8): 2028–2041.
  59. Baeyens L, Bonné S, Bos T, et al. Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro. Gastroenterology. 2009; 136(5): 1750–60.e13.
  60. Aïello V, Moreno-Asso A, Servitja JM, et al. Thyroid hormones promote endocrine differentiation at expenses of exocrine tissue. Exp Cell Res. 2014; 322(2): 236–248.
  61. Seymour PA. Sox9: a master regulator of the pancreatic program. Rev Diabet Stud. 2014; 11(1): 51–83.
  62. Manfroid I, Ghaye A, Naye F, et al. Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration. Dev Biol. 2012; 366(2): 268–278.
  63. Seymour PA, Freude KK, Dubois CL, et al. A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation. Dev Biol. 2008; 323(1): 19–30.
  64. Shih HP, Kopp JL, Sandhu M, et al. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. Development. 2012; 139(14): 2488–2499.
  65. Beer RL, Parsons MJ, Rovira M. Centroacinar cells: At the center of pancreas regeneration. Dev Biol. 2016; 413(1): 8–15.
  66. Parsons MJ, Pisharath H, Yusuff S, et al. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Dev. 2009; 126(10): 898–912.
  67. Ghaye AP, Bergemann D, Tarifeño-Saldivia E, et al. Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration. BMC Biol. 2015; 13: 70.
  68. Rovira M, Scott SG, Liss AS, et al. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci U S A. 2010; 107(1): 75–80.
  69. Ghazalli N, Wu X, Walker S, et al. Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro. Stem Cells Dev. 2018; 27(13): 898–909.
  70. Shih HP, Wang A, Sander M. Pancreas organogenesis: from lineage determination to morphogenesis. Annu Rev Cell Dev Biol. 2013; 29: 81–105.
  71. Georgia S, Bhushan A. Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest. 2004; 114(7): 963–968.
  72. Teta M, Rankin MM, Long SY, et al. Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev Cell. 2007; 12(5): 817–826.
  73. Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007; 117(9): 2553–2561.
  74. Cano DA, Rulifson IC, Heiser PW, et al. Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes. 2008; 57(4): 958–966.
  75. Desgraz R, Bonal C, Herrera PL. β-cell regeneration: the pancreatic intrinsic faculty. Trends Endocrinol Metab. 2011; 22(1): 34–43.
  76. Gregg BE, Moore PC, Demozay D, et al. Formation of a human β-cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab. 2012; 97(9): 3197–3206.
  77. Rieck S, Kaestner KH. Expansion of beta-cell mass in response to pregnancy. Trends Endocrinol Metab. 2010; 21(3): 151–158.
  78. Henquin JC, Rahier J. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia. 2011; 54(7): 1720–1725.
  79. Venkatesan V, Gopurappilly R, Goteti SK, et al. Pancreatic progenitors: The shortest route to restore islet cell mass. Islets. 2011; 3(6): 295–301.
  80. Puri S, Roy N, Russ HA, et al. Replication confers β cell immaturity. Nat Commun. 2018; 9(1): 485.
  81. Nielsen JH, Galsgaard ED, Møldrup A, et al. Regulation of beta-cell mass by hormones and growth factors. Diabetes. 2001; 50 Suppl 1: S25–S29.
  82. Ouziel-Yahalom L, Zalzman M, Anker-Kitai L, et al. Expansion and redifferentiation of adult human pancreatic islet cells. Biochem Biophys Res Commun. 2006; 341(2): 291–298.
  83. Thorel F, Népote V, Avril I, et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature. 2010; 464(7292): 1149–1154.
  84. Ye L, Robertson MA, Hesselson D, et al. Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development. 2015; 142(8): 1407–1417.
  85. Chung CH, Hao E, Piran R, et al. Pancreatic β-cell neogenesis by direct conversion from mature α-cells. Stem Cells. 2010; 28(9): 1630–1638.
  86. Cierpka-Kmiec K, Wronska A, Kmiec Z. 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.
  87. Brown ML, Andrzejewski D, Burnside A, et al. Activin Enhances α- to β-Cell Transdifferentiation as a Source For β-Cells In Male FSTL3 Knockout Mice. Endocrinology. 2016; 157(3): 1043–1054.
  88. Brown ML, Bonomi L, Ungerleider N, et al. Follistatin and follistatin like-3 differentially regulate adiposity and glucose homeostasis. Obesity (Silver Spring). 2011; 19(10): 1940–1949.
  89. Chakravarthy H, Gu X, Enge M, et al. Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx. Cell Metab. 2017; 25(3): 622–634.
  90. Adeghate E, Ponery AS. GABA in the endocrine pancreas: cellular localization and function in normal and diabetic rats. Tissue Cell. 2002; 34(1): 1–6.
  91. Ben-Othman N, Vieira A, Courtney M, et al. Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis. Cell. 2017; 168(1-2): 73–85.e11.
  92. Li J, Casteels T, Frogne T, et al. Artemisinins Target GABA Receptor Signaling and Impair α Cell Identity. Cell. 2017; 168(1-2): 86–100.e15.
  93. Ackermann AM, Moss NG, Kaestner KH. GABA and Artesunate Do Not Induce Pancreatic α-to-β Cell Transdifferentiation In Vivo. Cell Metab. 2018; 28(5): 787–792.e3.
  94. Shin JS, Kim JM, Min BH, et al. Absence of spontaneous regeneration of endogenous pancreatic β-cells after chemical-induced diabetes and no effect of GABA on α-to-β cell transdifferentiation in rhesus monkeys. Biochem Biophys Res Commun. 2019; 508(4): 1056–1061.
  95. Eizirik DL, Gurzov EN. Can GABA turn pancreatic α-cells into β-cells? Nat Rev Endocrinol. 2018; 14(11): 629–630.
  96. Muraro MJ, Dharmadhikari G, Grün D, et al. A Single-Cell Transcriptome Atlas of the Human Pancreas. Cell Syst. 2016; 3(4): 385–394.e3.
  97. Druelle N, Vieira A, Shabro A, et al. Ectopic expression of in pancreatic δ cells results in β-like cell neogenesis. J Cell Biol. 2017; 216(12): 4299–4311.
  98. Damia E, Chicharro D, Lopez S, et al. Adipose-Derived Mesenchymal Stem Cells: Are They a Good Therapeutic Strategy for Osteoarthritis? Int J Mol Sci. 2018; 19(7).
  99. Mendes Filho D, Ribeiro PDC, Oliveira LF, et al. Therapy With Mesenchymal Stem Cells in Parkinson Disease: History and Perspectives. Neurologist. 2018; 23(4): 141–147.
  100. Badimon L, Oñate B, Vilahur G. Adipose-derived Mesenchymal Stem Cells and Their Reparative Potential in Ischemic Heart Disease. Rev Esp Cardiol (Engl Ed). 2015; 68(7): 599–611.
  101. Carlsson PO, Schwarcz E, Korsgren O, et al. Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes. 2015; 64(2): 587–592.
  102. Okura H, Komoda H, Fumimoto Y, et al. Transdifferentiation of human adipose tissue-derived stromal cells into insulin-producing clusters. J Artif Organs. 2009; 12(2): 123–130.
  103. Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun. 2009; 32(1): 33–42.
  104. Cantarelli E, Pellegrini S, Citro A, et al. Bone marrow-and cord blood-derived stem cell transplantation for diabetes therapy. CellR4. 2015; 3(1): e1408.
  105. Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 2001; 50(3): 521–533.
  106. Karaoz E, Ayhan S, Gacar G, et al. Isolation and characterization of stem cells from pancreatic islet: pluripotency, differentiation potential and ultrastructural characteristics. Cytotherapy. 2010; 12(3): 288–302.
  107. Gong J, Zhang G, Tian F, et al. Islet-derived stem cells from adult rats participate in the repair of islet damage. J Mol Histol. 2012; 43(6): 745–750.
  108. Coskun E, Ercin M, Gezginci-Oktayoglu S. The Role of Epigenetic Regulation and Pluripotency-Related MicroRNAs in Differentiation of Pancreatic Stem Cells to Beta Cells. J Cell Biochem. 2018; 119(1): 455–467.
  109. Gao F, Wu Y, Wen H, et al. Multilineage potential research on pancreatic mesenchymal stem cells of bovine. Tissue Cell. 2019; 56: 60–70.
  110. 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): 263–274.
  111. 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): 1121–1133.
  112. Wang CY, Gou SM, Liu T, et al. Differentiation of CD24- pancreatic ductal cell-derived cells into insulin-secreting cells. Dev Growth Differ. 2008; 50(8): 633–643.
  113. Noguchi H, Naziruddin B, Shimoda M, et al. Induction of insulin-producing cells from human pancreatic progenitor cells. Transplant Proc. 2010; 42(6): 2081–2083.
  114. Huch M, Bonfanti P, Boj SF, et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J. 2013; 32(20): 2708–2721.
  115. Bonfanti P, Nobecourt E, Oshima M, et al. Ex Vivo Expansion and Differentiation of Human and Mouse Fetal Pancreatic Progenitors Are Modulated by Epidermal Growth Factor. Stem Cells Dev. 2015; 24(15): 1766–1778.
  116. Ma D, Tang S, Song J, et al. Culturing and transcriptome profiling of progenitor-like colonies derived from adult mouse pancreas. Stem Cell Res Ther. 2017; 8(1): 172.
  117. Movassat J, Beattie GM, Lopez AD, et al. Keratinocyte growth factor and beta-cell differentiation in human fetal pancreatic endocrine precursor cells. Diabetologia. 2003; 46(6): 822–829.
  118. Tokui Y, Kozawa J, Yamagata K, et al. Neogenesis and proliferation of beta-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector. Biochem Biophys Res Commun. 2006; 350(4): 987–993.
  119. Xu G, Kaneto H, Lopez-Avalos MD, et al. GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts. Diabetes Res Clin Pract. 2006; 73(1): 107–110.


Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: