Present and future cell therapies for pancreatic beta cell replenishment

World Journal of Gastroenterology

Volumn 18, Issue 47, 2012, Pages 6876-6884

  Domínguez Bendala, Juan ^a   Ricordi, Camillo ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Beta cell differentiation; Human embryonic stem cells; Induced pluripotent stem cells; Islet transplantation; Mesenchymal stem cells; Reprogramming

Indexed keywords

5' NUCLEOTIDASE; BRAIN DERIVED NEUROTROPHIC FACTOR; ENDOGLIN; FIBROBLAST GROWTH FACTOR 2; INSULIN; NERVE GROWTH FACTOR; NEUROGENIN 3; SCATTER FACTOR; SOMATOMEDIN C; THY 1 ANTIGEN; TRANSCRIPTION FACTOR MAFA; TRANSCRIPTION FACTOR PDX 1; VASCULOTROPIN;

ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL REGENERATION; CELL TRANSDIFFERENTIATION; DIABETES MELLITUS; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; MESENCHYMAL STEM CELL; NONHUMAN; NUCLEAR REPROGRAMMING; PANCREAS ISLET TRANSPLANTATION; PLURIPOTENT STEM CELL;

EID: 84873912337     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v18.i47.6876     Document Type: Article

References (137)

1. White SA, Manas DW. Pancreas transplantation. Ann R Coll Surg Engl 2008; 90: 368-370
2. Burke GW, Ciancio G, Sollinger HW. Advances in pancreas transplantation. Transplantation 2004; 77: S62-S67
3. Ricordi C, Strom TB. Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 2004; 4: 259-268
4. Inverardi L, Kenyon NS, Ricordi C. Islet transplantation: immunological perspectives. Curr Opin Immunol 2003; 15: 507-511
5. Merani S, Shapiro AM. Current status of pancreatic islet transplantation. Clin Sci (Lond) 2006; 110: 611-625
6. Murdoch TB, McGhee-Wilson D, Shapiro AM, Lakey JR. Methods of human islet culture for transplantation. Cell Transplant 2004; 13: 605-617
7. Pileggi A, Alejandro R, Ricordi C. Clinical islet transplantation. Minerva Endocrinol 2006; 31: 219-232
8. Seung E, Mordes JP, Greiner DL, Rossini AA. Induction of tolerance for islet transplantation for type 1 diabetes. Curr Diab Rep 2003; 3: 329-335
9. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes 1988; 37: 413-420
10. Korsgren O, Lundgren T, Felldin M, Foss A, Isaksson B, Permert J, Persson NH, Rafael E, Rydén M, Salmela K, Tibell A, Tufveson G, Nilsson B. Optimising islet engraftment is critical for successful clinical islet transplantation. Diabetologia 2008; 51: 227-232
11. Carlsson PO, Mattsson G. Oxygen tension and blood flow in relation to revascularization in transplanted adult and fetal rat pancreatic islets. Cell Transplant 2002; 11: 813-820
12. Carlsson PO, Palm F, Mattsson G. Low revascularization of experimentally transplanted human pancreatic islets. J Clin Endocrinol Metab 2002; 87: 5418-5423
13. Lammert E, Gu G, McLaughlin M, Brown D, Brekken R, Murtaugh LC, Gerber HP, Ferrara N, Melton DA. Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 2003; 13: 1070-1074
14. Fenn J, Raskino M. Mastering the hype cycle: how to choose the right innovation at the right time. Boston, Mass.: Harvard Business Press, 2008
15. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-238
16. Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54: 2060-2069
17. Bellin MD, Kandaswamy R, Parkey J, Zhang HJ, Liu B, Ihm SH, Ansite JD, Witson J, Bansal-Pakala P, Balamurugan AN, Papas KK, Sutherland DE, Moran A, Hering BJ. Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant 2008; 8: 2463-2470
18. Mosna F, Sensebé L, Krampera M. Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide. Stem Cells Dev 2010; 19: 1449-1470
19. Prabakar KR, Domínguez-Bendala J, Molano RD, Pileggi A, Villate S, Ricordi C, Inverardi L. Generation of glucoseresponsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplant 2012; 21: 1321-1339
20. Paredes B, Santana A, Arribas MI, Vicente-Salar N, de Aza PN, Roche E, Such J, Reig JA. Phenotypic differences during the osteogenic differentiation of single cell-derived clones isolated from human lipoaspirates. J Tissue Eng Regen Med 2011; 5: 589-599
21. Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes 2008; 57: 1759-1767
22. Wu Y, Chen L, Scott PG, Tredget EE. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 2007; 25: 2648-2659
23. Lin HT, Chiou SH, Kao CL, Shyr YM, Hsu CJ, Tarng YW, Ho LL, Kwok CF, Ku HH. Characterization of pancreatic stem cells derived from adult human pancreas ducts by fuorescence activated cell sorting. World J Gastroenterol 2006; 12: 4529-4535
24. Seeberger KL, Dufour JM, Shapiro AM, Lakey JR, Rajotte RV, Korbutt GS. Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab Invest 2006; 86: 141-153
25. Baertschiger RM, Bosco D, Morel P, Serre-Beinier V, Berney T, Buhler LH, Gonelle-Gispert C. Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development. Pancreas 2008; 37: 75-84
26. Timper K, Seboek D, Eberhardt M, Linscheid P, Christ-Crain M, Keller U, Müller B, Zulewski H. Human adipose tissuederived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun 2006; 341: 1135-1140
27. Okura H, Komoda H, Fumimoto Y, Lee CM, Nishida T, Sawa Y, Matsuyama A. Transdifferentiation of human adipose tissue-derived stromal cells into insulin-producing clusters. J Artif Organs 2009; 12: 123-130
28. Trovato L, De Fazio R, Annunziata M, Sdei S, Favaro E, Ponti R, Marozio L, Ghigo E, Benedetto C, Granata R. Pluripotent stem cells isolated from human amniotic fuid and differentiation into pancreatic beta-cells. J Endocrinol Invest 2009; 32: 873-876
29. Pessina A, Eletti B, Croera C, Savalli N, Diodovich C, Gribaldo L. Pancreas developing markers expressed on human mononucleated umbilical cord blood cells. Biochem Biophys Res Commun 2004; 323: 315-322
30. Sun B, Roh KH, Lee SR, Lee YS, Kang KS. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun 2007; 354: 919-923
31. Gao F, Wu DQ, Hu YH, Jin GX, Li GD, Sun TW, Li FJ. In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res 2008; 151: 293-302
32. Gao F, Wu DQ, Hu YH, Jin GX. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Chin Med J (Engl) 2008; 121: 811-818
33. Hu YH, Wu DQ, Gao F, Li GD, Yao L, Zhang XC. A secretory function of human insulin-producing cells in vivo. Hepatobiliary Pancreat Dis Int 2009; 8: 255-260
34. Wu XH, Liu CP, Xu KF, Mao XD, Zhu J, Jiang JJ, Cui D, Zhang M, Xu Y, Liu C. Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells. World J Gastroenterol 2007; 13: 3342-3349
35. Paz AH, Salton GD, Ayala-Lugo A, Gomes C, Terraciano P, Scalco R, Laurino CC, Passos EP, Schneider MR, Meurer L, Cirne-Lima E. Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats. Stem Cells Dev 2011; 20: 223-232
36. Moriscot C, de Fraipont F, Richard MJ, Marchand M, Savatier P, Bosco D, Favrot M, Benhamou PY. Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 2005; 23: 594-603
37. Phadnis SM, Joglekar MV, Dalvi MP, Muthyala S, Nair PD, Ghaskadbi SM, Bhonde RR, Hardikar AA. Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo. Cytotherapy 2011; 13: 279-293
38. Harris DT, Badowski M, Ahmad N, Gaballa MA. The potential of cord blood stem cells for use in regenerative medicine. Expert Opin Biol Ther 2007; 7: 1311-1322
39. Harris DT, Rogers I. Umbilical cord blood: a unique source of pluripotent stem cells for regenerative medicine. Curr Stem Cell Res Ther 2007; 2: 301-309
40. Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Müller B, Vallejo M, Thomas MK, Habener JF. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001; 50: 521-533
41. Huang H, Tang X. Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest 2003; 83: 539-547
42. Zhang L, Hong TP, Hu J, Liu YN, Wu YH, Li LS. Nestinpositive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol 2005; 11: 2906-2911
43. Ouziel-Yahalom L, Zalzman M, Anker-Kitai L, Knoller S, Bar Y, Glandt M, Herold K, Efrat S. Expansion and redifferentiation of adult human pancreatic islet cells. Biochem Biophys Res Commun 2006; 341: 291-298
44. Eberhardt M, Salmon P, von Mach MA, Hengstler JG, Brulport M, Linscheid P, Seboek D, Oberholzer J, Barbero A, Martin I, Müller B, Trono D, Zulewski H. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006; 345: 1167-1176
45. D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006; 24: 1392-1401
46. Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D'Amour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26: 443-452
47. Kelly OG, Chan MY, Martinson LA, Kadoya K, Ostertag TM, Ross KG, Richardson M, Carpenter MK, D'Amour KA, Kroon E, Moorman M, Baetge EE, Bang AG. Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nat Biotechnol 2011; 29: 750-756
48. Xu YX, Chen L, Wang R, Hou WK, Lin P, Sun L, Sun Y, Dong QY. Mesenchymal stem cell therapy for diabetes through paracrine mechanisms. Med Hypotheses 2008; 71: 390-393
49. Johansson U, Rasmusson I, Niclou SP, Forslund N, Gustavsson L, Nilsson B, Korsgren O, Magnusson PU. Formation of composite endothelial cell-mesenchymal stem cell islets: a novel approach to promote islet revascularization. Diabetes 2008; 57: 2393-2401
50. Fang B, Li N, Song Y, Li J, Zhao RC, Ma Y. Cotransplantation of haploidentical mesenchymal stem cells to enhance engraftment of hematopoietic stem cells and to reduce the risk of graft failure in two children with severe aplastic anemia. Pediatr Transplant 2009; 13: 499-502
51. Lee ST, Maeng H, Chwae YJ, Oh DJ, Kim YM, Yang WI. Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model. Int J Hematol 2008; 87: 327-337
52. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 2007; 110: 2764-2767
53. Noort WA, Kruisselbrink AB, In'tanker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MH, Löwik CW, Falkenburg JH, Willemze R, Fibbe WE. Mesenchymal stem cells promote engraftment of human umbilical cord bloodderived CD34(+) cells in NOD/SCID mice. Exp Hematol 2002; 30: 870-878
54. Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simões BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 2007; 297: 1568-1576
55. Couri CE, Voltarelli JC. Autologous stem cell transplantation for early type 1 diabetes mellitus. Autoimmunity 2008; 41: 666-672
56. Estrada EJ, Valacchi F, Nicora E, Brieva S, Esteve C, Echevarria L, Froud T, Bernetti K, Cayetano SM, Velazquez O, Alejandro R, Ricordi C. Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus. Cell Transplant 2008; 17: 1295-1304
57. Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005; 28: 2155-2160
58. Domínguez-Bendala J. Pancreatic stem cells. 1st ed. New York: Humana Press, 2009: 1-254
59. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004; 22: 1115-1124
60. Smukler SR, Arntfield ME, Razavi R, Bikopoulos G, Karpowicz P, Seaberg R, Dai F, Lee S, Ahrens R, Fraser PE, Wheeler MB, van der Kooy D. The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 2011; 8: 281-293
61. Cardinale V, Wang Y, Carpino G, Cui CB, Gatto M, Rossi M, Berloco PB, Cantafora A, Wauthier E, Furth ME, Inverardi L, Dominguez-Bendala J, Ricordi C, Gerber D, Gaudio E, Alvaro D, Reid L. Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. Hepatology 2011; 54: 2159-2172
62. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292: 154-156
63. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981; 78: 7634-7638
64. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-1147
65. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 2001; 292: 1389-1394
66. Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Håkansson J, Fleckner J, Sköld HN, Melton D, Semb H, Serup P. Artifactual insulin release from differentiated embryonic stem cells. Diabetes 2004; 53: 2603-2609
67. 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: 1534-1541
68. Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M, Woo S, Fehling HJ, Keller G. Development of definitive endoderm from embryonic stem cells in culture. Development 2004; 131: 1651-1662
69. McLean AB, D'Amour KA, Jones KL, Krishnamoorthy M, Kulik MJ, Reynolds DM, Sheppard AM, Liu H, Xu Y, Baetge EE, Dalton S. 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
70. Basford CL, Prentice KJ, Hardy AB, Sarangi F, Micallef SJ, Li X, Guo Q, Elefanty AG, Stanley EG, Keller G, Allister EM, Nostro MC, Wheeler MB. The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells. Diabetologia 2012; 55: 358-371
71. Tang C, Lee AS, Volkmer JP, Sahoo D, Nag D, Mosley AR, Inlay MA, Ardehali R, Chavez SL, Pera RR, Behr B, Wu JC, Weissman IL, Drukker M. An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol 2011; 29: 829-834
72. Lewitzky M, Yamanaka S. Reprogramming somatic cells towards pluripotency by defined factors. Curr Opin Biotechnol 2007; 18: 467-473
73. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008; 26: 101-106
74. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 2008; 322: 949-953
75. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2007; 2: 3081-3089
76. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-872
77. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676
78. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA. Human induced pluripotent stem cells free of vector and transgene sequences. Science 2009; 324: 797-801
79. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318: 1917-1920
80. Izpisúa Belmonte JC, Ellis J, Hochedlinger K, Yamanaka S. Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nat Rev Genet 2009; 10: 878-883
81. Narazaki G, Uosaki H, Teranishi M, Okita K, Kim B, Matsuoka S, Yamanaka S, Yamashita JK. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation 2008; 118: 498-506
82. Okita K, Ichisaka T, Yamanaka S. Generation of germlinecompetent induced pluripotent stem cells. Nature 2007; 448: 313-317
83. Mason C, Manzotti E. Induced pluripotent stem cells: an emerging technology platform and the Gartner hype cycle. Regen Med 2009; 4: 329-331
84. Bar-Nur O, Russ HA, Efrat S, Benvenisty N. 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
85. Feng Q, Lu SJ, Klimanskaya I, Gomes I, Kim D, Chung Y, Honig GR, Kim KS, Lanza R. Hemangioblastic derivatives from human induced pluripotent stem cells exhibit limited expansion and early senescence. Stem Cells 2010; 28: 704-712
86. Gore A, Li Z, Fung HL, Young JE, Agarwal S, AntosiewiczBourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011; 471: 63-67
87. Pera MF. Stem cells: The dark side of induced pluripotency. Nature 2011; 471: 46-47
88. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brüstle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T. Copy number variation and selection during reprogramming to pluripotency. Nature 2011; 471: 58-62
89. Tateishi K, He J, Taranova O, Liang G, D'Alessio AC, Zhang Y. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 2008; 283: 31601-31607
90. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 2009; 4: 472-476
91. Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Schöler HR, Duan L, Ding S. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 2009; 4: 381-384
92. Jia F, Wilson KD, Sun N, Gupta DM, Huang M, Li Z, Panetta NJ, Chen ZY, Robbins RC, Kay MA, Longaker MT, Wu JC. A nonviral minicircle vector for deriving human iPS cells. Nat Methods 2010; 7: 197-199
93. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly Efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modifed mRNA. Cell Stem Cell 2010; 7: 618-630
94. Shi Y, Desponts C, Do JT, Hahm HS, Schöler HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 2008; 3: 568-574
95. Rao MS, Dwivedi RS, Subbarao V, Usman MI, Scarpelli DG, Nemali MR, Yeldandi A, Thangada S, Kumar S, Reddy JK. Almost total conversion of pancreas to liver in the adult rat: a reliable model to study transdifferentiation. Biochem Biophys Res Commun 1988; 156: 131-136
96. Rao MS, Reddy JK. Hepatic transdifferentiation in the pancreas. Semin Cell Biol 1995; 6: 151-156
97. Rao MS, Subbarao V, Reddy JK. Induction of hepatocytes in the pancreas of copper-depleted rats following copper repletion. Cell Differ 1986; 18: 109-117
98. Lee BC, Hendricks JD, Bailey GS. Metaplastic pancreatic cells in liver tumors induced by diethylnitrosamine. Exp Mol Pathol 1989; 50: 104-113
99. Shen CN, Slack JM, Tosh D. Molecular basis of transdifferentiation of pancreas to liver. Nat Cell Biol 2000; 2: 879-887
100. Nordlie RC, Foster JD, Lange AJ. Regulation of glucose production by the liver. Annu Rev Nutr 1999; 19: 379-406
101. Kim HI, Ahn YH. Role of peroxisome proliferator-activated receptor-gamma in the glucose-sensing apparatus of liver and beta-cells. Diabetes 2004; 53 Suppl 1: S60-S65
102. Melton D. Signals for tissue induction and organ formation in vertebrate embryos. Harvey Lect 1997-1998; 93: 49-64
103. Deutsch G, Jung J, Zheng M, Lóra J, Zaret KS. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001; 128: 871-881
104. Jung J, Zheng M, Goldfarb M, Zaret KS. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 1999; 284: 1998-2003
105. Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev 2004; 14: 582-590
106. Tremblay KD, Zaret KS. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 2005; 280: 87-99
107. Yoshitomi H, Zaret KS. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 2004; 131: 807-817
108. Zaret KS. Hepatocyte differentiation: from the endoderm and beyond. Curr Opin Genet Dev 2001; 11: 568-574
109. Zaret KS. Liver specification and early morphogenesis. Mech Dev 2000; 92: 83-88
110. Wells JM, Melton DA. Vertebrate endoderm development. Annu Rev Cell Dev Biol 1999; 15: 393-410
111. Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS. Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 1996; 10: 1670-1682
112. Douarin NM. An experimental analysis of liver development. Med Biol 1975; 53: 427-455
113. Cardinale V, Wang Y, Carpino G, Alvaro D, Reid L, Gaudio E. Multipotent stem cells in the biliary tree. Ital J Anat Embryol 2010; 115: 85-90
114. Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994; 371: 606-609
115. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. betacell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 1998; 12: 1763-1768
116. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N, Karasik A. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocininduced hyperglycemia. Nat Med 2000; 6: 568-572
117. Ber I, Shternhall K, Perl S, Ohanuna Z, Goldberg I, Barshack I, Benvenisti-Zarum L, Meivar-Levy I, Ferber S. Functional, persistent, and extended liver to pancreas transdifferentiation. J Biol Chem 2003; 278: 31950-31957
118. Meivar-Levy I, Sapir T, Gefen-Halevi S, Aviv V, Barshack I, Onaca N, Mor E, Ferber S. Pancreatic and duodenal homeobox gene 1 induces hepatic dedifferentiation by suppressing the expression of CCAAT/enhancer-binding protein beta. Hepatology 2007; 46: 898-905
119. Tang DQ, Lu S, Sun YP, Rodrigues E, Chou W, Yang C, Cao LZ, Chang LJ, Yang LJ. Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1and Pdx1-VP16 mediated by lentiviral vectors. Lab Invest 2006; 86: 83-93
120. Wang AY, Ehrhardt A, Xu H, Kay MA. Adenovirus transduction is required for the correction of diabetes using Pdx-1 or Neurogenin-3 in the liver. Mol Ther 2007; 15: 255-263
121. Kaneto H, Matsuoka TA, Nakatani Y, Miyatsuka T, Matsuhisa M, Hori M, Yamasaki Y. A crucial role of MafA as a novel therapeutic target for diabetes. J Biol Chem 2005; 280: 15047-15052
122. Kaneto H, Miyatsuka T, Fujitani Y, Noguchi H, Song KH, Yoon KH, Matsuoka TA. Role of PDX-1 and MafA as a potential therapeutic target for diabetes. Diabetes Res Clin Pract 2007; 77 Suppl 1: S127-S137
123. Kaneto H, Miyatsuka T, Shiraiwa T, Yamamoto K, Kato K, Fujitani Y, Matsuoka TA. Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells. Curr Med Chem 2007; 14: 1745-1752
124. Matsuoka TA, Kaneto H, Stein R, Miyatsuka T, Kawamori D, Henderson E, Kojima I, Matsuhisa M, Hori M, Yamasaki Y. MafA regulates expression of genes important to islet betacell function. Mol Endocrinol 2007; 21: 2764-2774
125. Miyatsuka T, Kaneto H, Kajimoto Y, Hirota S, Arakawa Y, Fujitani Y, Umayahara Y, Watada H, Yamasaki Y, Magnuson MA, Miyazaki J, Hori M. Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis. Biochem Biophys Res Commun 2003; 310: 1017-1025
126. Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003; 9: 596-603
127. Horb ME, Shen CN, Tosh D, Slack JM. Experimental conversion of liver to pancreas. Curr Biol 2003; 13: 105-115
128. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 2008; 455: 627-632
129. Aramata S, Han SI, Kataoka K. Roles and regulation of transcription factor MafA in islet beta-cells. Endocr J 2007; 54: 659-666
130. Aramata S, Han SI, Yasuda K, Kataoka K. Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1. Biochim Biophys Acta 2005; 1730: 41-46
131. Zhao L, Guo M, Matsuoka TA, Hagman DK, Parazzoli SD, Poitout V, Stein R. The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. J Biol Chem 2005; 280: 11887-11894
132. Lee SH, Hao E, Savinov AY, Geron I, Strongin AY, ItkinAnsari P. Human beta-cell precursors mature into functional insulin-producing cells in an immunoisolation device: implications for diabetes cell therapies. Transplantation 2009; 87: 983-991
133. Fort A, Fort N, Ricordi C, Stabler CL. Biohybrid devices and encapsulation technologies for engineering a bioartificial pancreas. Cell Transplant 2008; 17: 997-1003
134. Lin G, OuYang Q, Zhou X, Gu Y, Yuan D, Li W, Liu G, Liu T, Lu G. A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure. Cell Res 2007; 17: 999-1007
135. Revazova ES, Turovets NA, Kochetkova OD, Agapova LS, Sebastian JL, Pryzhkova MV, Smolnikova VI, Kuzmichev LN, Janus JD. HLA homozygous stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 2008; 10: 11-24
136. Melnikova I. RNA-based therapies. Nat Rev Drug Discov 2007; 6: 863
137. Osman EY, Yen PF, Lorson CL. Bifunctional RNAs targeting the intronic splicing silencer N1 increase SMN levels and reduce disease severity in an animal model of spinal muscular atrophy. Mol Ther 2012; 20: 119-126