Stem cell transplantation supports the repair of injured olfactory Neuroepithelium after permanent lesion

Trends in Stem Cell Biology and Technology

Volumn , Issue , 2009, Pages 283-297

  Franceschini, Valeria ^a   Bettini, Simone ^a   Saccardi, Riccardo ^a   Revoltella, Roberto P ^a  

^a CNR   (Italy)

Author keywords

Neuro olfactory epithelium; Olfaction; Stem cell; Tissue regeneration; Transplantation

Indexed keywords

EID: 84900236159     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-60327-905-5_16     Document Type: Chapter

References (142)

1. Farbman AI. Cell biology of olfaction. Cambridge University Press, Cambridge, 1992 .
2. Ding XX, Coon MJ. Purification and characterization of two unique forms of cytochrome P 450 from rabbit nasal microsomes. Biochemistry 1988; 27: 8330-7 .
3. Chen Y, Getchell ML, Ding X, et al. Immunolocalization of two cytochrome P450 isozymes in rat nasal chemosensory tissue. Neuroreport 1992; 3: 749-52 .
4. Suzuki Y, Schafer J, Farbman AI. Phagocytic cells in the rat olfactory epithelium after bulbectomy. Exp Neurol 1995; 136: 225-33 .
5. Suzuki Y, Takeda M, Farbman AI. Supporting cells as phagocytes in the olfactory epithelium after bulbectomy. J Comp Neurol 1996; 376: 509-17 .
6. Huard JM, Schwob JE. Cell cycle of globose basal cells in rat olfactory epithelium. Dev Dyn 1995; 203: 17-26 .
7. Calderon-Garciduenas L, Rodriguez-Alcaraz A, Villarreal-Calderon A, et al. Nasal epithelium as a sentinel for airborne environmental pollution. Toxicol Sci 1998; 46: 352-64 .
8. Graziadei, PPC, Monti Graziadei GA. Continuous nerve cell renewal in the olfactory system. In: Jacobson M, editor. Handbook of sensory physiology. Vol. 9 Development of sensory systems. Springer, New York, 1978: 55-83 .
9. Farbman AI. Olfactory neurogenesis: genetic or environmental controls? Trends Neurosci 1990; 13: 362-5 .
10. Beyers DW, Farmer MS. Effects of copper on olfaction of Colorado pikeminnow. Environ Toxicol Chem 2001; 20: 907-12 .
11. Baldwin DH, Sandhal JF, Labenia JS, et al. Sublethal effect of copper on coho salmon: impacts on nonoverlapping receptor pathways in the peripheral olfactory nervous system. Environ Toxicol Chem 2003; 22: 2266-74 .
12. Schwob JE, Youngentob SL, Mezza RC. Reconstitution of the rat olfactory epithelium after methyl bromide-induced lesion. J Comp Neurol 1995; 359: 15-37 .
13. Bergman U, Brittebo EB. Methimazole toxicity in rodents: covalent binding in the olfactory mucosa and detection of glial fibrillary acidic protein in the olfactory bulb. Toxicol Appl Pharmacol 1999; 155: 190-200 .
14. Brandt I, Brittebo EB, Feil VJ, et al. Irreversible binding and toxicity of the herbicide dichlorobenil (2,6-dichlorobenzonitrile) in the olfactory mucosa of mice. Toxicol Appl Pharmacol 1990; 103: 491-501.
15. Bergman U, Ostergren A, Gustafson A-L, et al. Differential effects of olfactory toxicants on olfactory regeneration. Arch Toxicol 2002; 76: 104-12 .
16. Buckland ME, Cunningham AM. Alterations in expression of the neurotrophic factors glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophicfactor, in the target-deprived olfactory neuroepithelium. Neuroscience 1999; 90: 333-47 .
17. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-7 .
18. Strem BM, Hicok KC, Zhu M, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 2005; 54: 132-41 .
19. Mizuno H, Zuk PA, Zhu M, et al. Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg 2002; 109: 199-209 .
20. Van Damme EJM, Peumans WJ, Pusztai A, et al. Handbook of plant lectins: properties and biomedical applications. Wiley, Chichester, England, 1998 .
21. Ricci U, Sani I, Guarducci S, et al. Infrared fluorescent automated detection of thirteen short tandem repeat polymorphisms and one gender-determining system of the CODIS core system. Electrophoresis 2000; 213: 564-70 .
22. Taniguchi K, Saito H, Okamura M, et al. Immunohistochemical demonstration of protein gene product 9.5 (PGP 9.5) in the primary olfactory system of the rat. Neurosci Lett 1993; 156: 24-6 .
23. Johnson EW, Eller PM, Jafek BW. Protein gene product 9.5 in the developing and mature rat vomeronasal organ. Dev Brain Res 1994; 78: 259-64 .
24. Schofield JN, Day INM, Thompson RJ, et al. PGP 9.5, a ubiquitin C-Terminal hydrolase; pattern of mRNA and protein expression during neural development in the mouse. Dev Brain Res 1995; 85: 229-38 .
25. Key B, Akeson RA. Olfactory neurons express a unique glycosylated form of the neural cell adhesion molecule NCAM. J Cell Biol 1990; 110: 1729-43 .
26. Key B, Akeson RA. Immunochemical markers for the frog olfactory neuroepithelium. Dev Brain Res 1990; 57: 103-17 .
27. Breer H. Molecular reaction cascade in olfactory signal transduction. J Steroid Biochem Mol Biol 1991; 39: 621-5 .
28. Franceschini V, Lazzari M, Revoltella RP, et al. Histochemical study by lectin binding of surface glycoconjugates in the developing olfactory system of rat. Int J Dev Neurosci 1994; 12: 197-206 .
29. Lipscomb BW, Treolar HB, Klehoff J, et al. Cell surface carbohydrates and glomerular targeting of olfactory sensory neuron axons in the mouse. J Comp Neurol 2003; 467: 22-31 .
30. Henion TR, Raitcheva D, Grosholz R, et al. b 1,3- N - Acetylglucosaminyltransferase 1 glycosilation is required for axon pathfinding by olfactory sensory neurons. J Neurosci 2005; 25: 1894-903 .
31. St. John J, Key B. A model for axonal navigation based on glycocodes in the primary olfactory system. Chem Senses 2005; 30 Suppl 1: i123-4 .
32. Hao HN, Zhao J, Thomas RL, et al. Fetal human hemopoietic stem cells can differentiate sequentially into neural stem cells and then astrocytes in vitro. J Hematother Stem Cell Res 2003; 12: 23-32 .
33. Baal N, Reisinger K, Jahr H, et al. Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood. Thromb Haemost 2004; 92: 767-75 .
34. Nan B, Getchell ML, Partin JV, et al. Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J Comp Neurol 2001; 435: 60-77 .
35. Getchell TV, Shah DS, Partin JV, et al. Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation. J Neurosci Res 2002; 67: 246-54 .
36. Getchell TV, Subhedar NK, Shah DS, et al. Chemokine regulation of macrophage recruitment into the olfactory epithelium following target ablation: involvement of macrophage inflammatory protein-1 and monocyte chemoattractant protein-1. J Neurosci Res 2002; 70: 784-93.
37. Bauer S, Rasika S, Han J, et al. Leukemia inhibitory factor is a key signal for injury-induced neurogenesis in the adult mouse olfactory epithelium. J Neurosci 2003; 23: 1792-803 .
38. Michelini M, Franceschini V, Sihui Chen S, et al. Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems. Cell Prolif 2006; 39: 217-29 .
39. Awenagha O, Campbell G, Bird MM. Distribution of GAP-43, b -III tubulin and F-Actin in developing and regenerating axons and their growth cones in vitro, following neurotrophin treatment. J Neurocyt 2003; 32: 1077-89
40. DeFronzo RA, Ferrannini E, Keen H, et al. International textbook of diabetes mellitus, 3th ed. Wiley, Chichester, UK, 2004 .
41. Isermann B, Ritzel R, Zorn M, Schilling T, Nawroth PP. Autoantibodies in diabetes mellitus: current utility and perspectives. Exp Clin Endocrinol Diabetes 2007; 115: 483-90 .
42. Prentki M, Joly E, El-Assaad W, Roduit R. Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes 2002; 51: S405-13 .
43. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-8 .
44. Roche E, Reig JA, Campos A, et al. Insulin-secreting cells derived from stem cells: clinical perspectives, hypes and hopes. Transplant Immunol 2005; 15: 113-29 .
45. Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54: 2060-9 .
46. Hermann M, Margreiter R, Hengster P. Molecular and cellular key players in human islet transplantation. J Cell Mol Med 2007; 11: 398-415 .
47. Laybutt DR, Hawkins YC, Lock J, et al. Influence of diabetes on the loss of b -cell differentiation after islet transplantation in rats. Diabetologia 2007; 50: 2117-25 .
48. Marzorati S, Pileggi A, Ricordi C. Allogeneic islet transplantation. Expert Opin Biol Ther 2007; 7: 1627-45 .
49. Kaestner KH. Beta cell transplantation and immunosuppression: cant live with it, cant live without it. J Clin Invest 2007; 117: 2380-2 .
50. Smith AG. Embryo-derived stem cells of mice and men. Annu Rev Cell Dev Biol 2001; 17: 435-62 .
51. Smith AG. Culture and differentiation of embryonic stem cells. J Tissue Culture Methods 1991; 13: 89-94 .
52. Prowse AB, McQuade LR, Bryant KJ, Marcal H, Gray PP. Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. J Proteome Res 2007; 6: 3796-807 .
53. Roche E, Sepulcre P, Reig JA, Santana A, Soria B. Ectodermal commitment of insulinproducing cells derived from mouse embryonic stem cells. FASEB J 2005; 19: 1341-3 .
54. Ensenat-Waser R, Santana A, Vicente-Salar N, et al. Isolation and characterization of residual undifferentiated mouse embryonic stem cells from embryoid body cultures by fluorescence tracking. In Vitro Cell Develop Biol Animal 2006; 42: 115-23 .
55. Kahan BW, Jacobson LM, Hullett DA, et al. Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells. An in vitro model to study islet differentiation. Diabetes 2003; 52: 2016-24.
56. Skoudy A, Rovira M, Savatier P, et al. Transforming growth factor (TGF) b, fibroblast growth factor (FGF) and retinoid signaling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells. Biochem J 2004; 379: 749-56 .
57. Ensenat-Waser R, Santana A, Paredes B, et al. Embryonic stem cell processing in obtaining insulin-producing cells: a technical review. Cell Preserv Technol 2006; 4: 278-89 .
58. Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science 2000; 287: 1427-30 .
59. Barrilleaux B, Phinney DG, Prockop DJ, OConnor KC. Ex vivo engineering of living tissues with adult stem cells. Tissue Eng 2006; 12: 3007-19 .
60. Fellous TG, Guppy NJ, Brittan M, Alison MR. Cellular pathways to b -cell replacement. Diabetes/Metab Res Rev 2007; 23: 87-99 .
61. Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003; 111: 843-50 .
62. Hess D, Li L, Martin M, et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 2003; 21: 763-70 .
63. Ferber S, Halkin A, Cohen H, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000; 6: 568-72 .
64. Kojima H, Fujimiya M, Matsumura K, et al. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003; 9: 596-603 .
65. Soria B, Roche E, Bernat G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000; 49: 157-62 .
66. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes 2001; 50: 1691-7 .
67. Lumelsky N, Blondel O, Laeng P, et al. Differentiation of embryonic stem cells to insulinsecreting structures similar to pancreatic islets. Science 2001;292:1389-94.
68. Jones EA, Tosh D, Wilson DI, Lindsay S, Forrester LM. Hepatic differentiation of murine embryonic stem cells. Exp Cell Res 2002; 272: 15-22 .
69. Shiroi A, Yoshikawa M, Yokota H, et al. Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone. Stem Cells 2002; 20: 284-92 .
70. Kubo A, Shinozaki K, Shannon JM, et al. Development of definitive endoderm from embryonic stem cells in culture. Development 2004; 131: 1651-62 .
71. Ku HT, Zhang N, Kubo A, et al. Committing embryonic stem cells to early endocrine pancreas in vitro. Stem Cells 2004; 22: 1205-17 .
72. DAmour 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: 1534-41 .
73. Ishii T, Yasuchika K, Fujii H, et al. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes. Exp Cell Res 2005; 309: 68-77 .
74. Milne HM, Burns CJ, Kitsou-Mylona I, et al. Generation of insulin-expressing cells from mouse embryonic stem cells. Biochem Biophys Res Commun 2005; 328: 399-403 .
75. Tada S, Era T, Furusawa C, et al. Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture. Development 2005; 132: 4363-74 .
76. Yasunaga M, Tada S, Torikai-Nishikawa S, et al. Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 2005; 23: 1542-50 .
77. DAmour KA, Bang AG, Eliazer S, et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006; 24: 1392-401 .
78. Gadue P, Huber TL, Paddison PJ, Keller GM. Wnt and TGF- b signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells. Proc Natl Acad Sci U S A 2006; 103: 16806-11 .
79. Gouon-Evans V, Boussemart L, Gadue P, et al. BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nat Biotechnol 2006; 24: 1402-11 .
80. Jiang W, Shi Y, Zhao D, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res 2007; 17: 333-44.
81. Nakanishi M, Hamazaki TS, Komazaki S, Okochi H, Asashima M. Pancreatic tissue formation from murine embryonic stem cells in vitro. Differentiation 2007; 75: 1-11 .
82. Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA. Insulin staining of ES cell progeny from insulin uptake. Science 2003; 299: 363 .
83. Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 2002; 99: 16105-10 .
84. Moritoh Y, Yamato E, Yasui Y, Miyazaki S, Miyazaki J. Analysis of insulin-producing cells during in vitro differentiation from feeder-free embryonic stem cells. Diabetes 2003; 52: 1163-8 .
85. Blyszczuk P, Czyz J, Kania G, et al. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci U S A 2003; 100: 998-1003 .
86. Santana A, Enseat-Waser R, Arribas MI, Reig JA, Roche E. Insulin-producing cells derived from stem cells: recent progress and future directions. J Cell Mol Med 2006; 10: 866-83 .
87. Madsen OD, Serup P. Towards cell therapy for diabetes. Nat Biotechnol 2006; 24: 1481-3 .
88. Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 2003; 120: 1351-83 .
89. Yamanaka Y, Ralston A, Stephenson RO, Rossant J. Cell and molecular regulation of the mouse blastocyst. Dev Dyn 2006; 235: 2301-14 .
90. Inman KE, Downs KM. Localization of brachyury (T) in embryonic and extraembryonic tissues during mouse gastrulation. Gene Expr Patterns 2006; 6: 783-93 .
91. Wang L, Schulz TC, Sherrer ES, et al. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling. Blood 2007; 110: 4111-9 .
92. Nguyen TT, Sheppard AM, Kaye PL, Noakes PG. IGF-1 and insulin activate mitogen-Activated protein kinase via the type 1 IGF receptor in mouse embryonic stem cells. Reproduction 2007; 134: 41-9 .
93. McLean AB, DAmour 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 .
94. Schroeder IS, Rolletschek A, Blyszczuk P, Kania G, Wobus AM. Differentiation of mouse embryonic stem cells to insulin-producing cells. Nat Protocols 2006; 1: 495-507 .
95. Mfopou JK, De Groote V, Xu X, Heimberg H, Bouwens L. Sonic hedgehog and other soluble factors from differentiating embryoid bodies inhibit pancreas development. Stem Cells 2007; 25: 1156-65 .
96. Broln GKC, Heins N, Edsbagge J, Semb H. Signals from the embryonic mouse pancreas induce differentiation of human embryonic stem cells into insulin-producing b -cell-like cells. Diabetes 2005; 54: 2867-74 .
97. Rivas-Carrillo JD, Okitsu T, Tanaka N, Kobayashi N. Pancreas development and beta-cell differentiation of embryonic stem cells. Curr Med Chem 2007; 14: 1573-8 .
98. Vaca P, Martin F, Vegara-Meseguer JM, Rovira JM, Berna G, Soria B. Induction of differentiation of embryonic stem cells into insulin secreting cells by fetal soluble factors. Stem Cells 2006; 24: 258-65 .
99. Bonner-Weir S, Taneja M, Weir GC, et al. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 2000; 97: 7999-8004 .
100. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. Reversal of insulindependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000; 6: 278-82 .
101. 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: 521-33 .
102. Hao E, Tyrberg B, Itkin-Ansari P, et al. Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 2006; 12: 310-6 .
103. Taguchi M, Yamaguchi T, Otsuki M. Induction of PDX-1-positive cells in the main duct during regeneration after acute necrotizing pancreatitis in rats. J Pathol 2002; 197: 638-46.
104. Kritzik MR, Jones E, Chen Z, et al. PDX-1 and Msx-2 expression in the regenerating and developing pancreas. J Endocrinol 1999; 163: 523-30 .
105. Roche E, Jones J, Arribas MI, Leon-Quinto T, Soria B. Role of small bioorganic molecules in stem cell differentiation to insulin-producing cells. Bioorg Med Chem 2006; 14: 6466-74 .
106. Rafaeloff R, Pittenger GL, Barlow SW, et al. Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters. J Clin Invest 1997; 99: 2100-9 .
107. Zulewski H. Stem cells with potential to generate insulin-producing cells in man. Swiss Med Wkly 2006; 136: 647-54 .
108. Gershengorn MC, Hardikar AA, Hardikar A, Geras-Raaka E, Marcus-Samuels B, Raaka BM. Epithelial-To-mesenchymal transition generates proliferative human islet precursor cells. Science 2004; 306: 2261-4 .
109. Davani B, Ikonomou L, Raaka BM, et al. Human islet-derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone-expressing cells in vivo. Stem Cells 2007; 25: 3215 .
110. Atouf F, Park CH, Pechhold K, Ta M, Choi Y, Lumelsky NL. No evidence for mouse pancreatic beta-cell epithelial-mesenchymal transition in vitro. Diabetes 2007; 56: 699-702 .
111. Chase LG, Ulloa-Montoya F, Kidder BL, Verfaillie CM. Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal transition from Pdx-1 or insulin-positive cells. Diabetes 2007; 56: 3-7 .
112. Eberhardt M, Salmon P, von Mach MA, et al. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006; 345: 1167-76 .
113. Weinberg N, Ouziel-Yahalom L, Knoller S, Efrat S, Dor Y. Lineage tracing evidence for in vitro dedifferentiation but rare proliferation of mouse pancreatic beta-cells. Diabetes 2007; 56: 1299-304 .
114. DAlessandro JS, Lu K, Fung BP, Colman A, Clarke DL. Rapid and efficient in vitro generation of pancreatic islet progenitor cells from nonendocrine epithelial cells in the adult human pancreas. Stem Cells Dev 2007; 16: 75-89 .
115. Minami K, Okuno M, Miyawaki K, et al. Lineage tracing and characterization of insulinsecreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci U S A 2005; 102: 15116-21 .
116. Desai BM, Oliver-Krasinski J, De Leon DD, et al. Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell regeneration. J Clin Invest 2007; 117: 971-7 .
117. Ackermann AM, Gannon M. Molecular regulation of pancreatic b -cell mass development, maintenance, and expansion. J Mol Endocrinol 2007; 38: 193-206 .
118. Murtaugh LC. Pancreas and beta-cell development: from the actual to the possible. Development 2007; 134: 427-38 .
119. Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic b -cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004; 429: 41-6 .
120. Kodama S, Kuhtreiber W, Fujimura S, Dale EA, Faustman DL. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 2003; 302: 1223-7 .
121. Banerjee M, Kanitkar M, Bhonde RR. Approaches towards endogenous pancreatic regeneration. Rev Diab Stud 2005; 2: 165-76 .
122. Efrat S. Prospects for gene therapy of insulin-dependent diabetes mellitus. Diabetologia 1998; 41: 1401-9 .
123. Choi JB, Uchino H, Azuma K, et al. Little evidence of transdifferentiation of bone marrowderived cells into pancreatic beta cells. Diabetologia 2003; 46: 1366-74 .
124. Lechner A, Yang Y-Q, Blacken RA, Wang L, Nolan AL, Habener JF. No evidence for significant transdifferentiation of bone marrow into pancreatic b -cells in vivo. Diabetes 2004; 53: 616-23 .
125. Hasegawa Y, Ogihara T, Yamada T, et al. Bone marrow (BM) transplantation promotes beta-cell regeneration after acute injury through BM cell mobilization. Endocrinology 2007; 148: 2006-15 .
126. Butler AE, Huang A, Rao PN, et al. Hematopoietic stem cells derived from adult donors are not a source of pancreatic beta-cells in adult nondiabetic humans. Diabetes 2007; 56: 1810-6.
127. Lavazais E, Pogu S, Sai P, Martignat L. Cytokine mobilization of bone marrow cells and pancreatic lesion do not improve streptozotocin-induced diabetes in mice by transdifferentiation of bone marrow cells into insulin-producing cells. Diabetes Metab 2007; 33: 68-78 .
128. DIppolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 2004; 117: 2971-81 .
129. Tayaramma T, Ma B, Rohde M, Mayer H. Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells. Stem Cells 2006; 24: 2858-67 .
130. Moriscot C, de Fraipont F, Richard MJ, et al. 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: 594-604 .
131. Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 2007; 25: 2837-44 .
132. Yu S, Li C, Xin-guo H, et al. Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J (Engl) 2007; 120: 771-6 .
133. Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun 2006; 341: 1135-40 .
134. Ruhnke M, Ungefroren H, Nussler A, et al. Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 2005; 128: 1774-86 .
135. Zhao Y, Huang Z, Lazzarini P, Wang Y, Di A, Chen M. A unique human blood-derived cell population displays high potential for producing insulin. Biochem Biophys Res Commun 2007; 360: 205-11 .
136. Yang L, Li S, Hatch H, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A 2002; 99: 8078-83 .
137. Kim S, Shin JS, Kim HJ, Fisher RC, Lee MJ, Kim CW. Streptozotocin-induced diabetes can be reversed by hepatic oval cell activation through hepatic transdifferentiation and pancreatic islet regeneration. Lab Invest 2007; 87: 702-12 .
138. Zalzman M, Gupta S, Giri RK, et al. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci U S A 2003; 100: 7253-8 .
139. Shternhall-Ron K, Quintana FJ, Perl S, et al. Ectopic PDX-1 expression in liver ameliorates type 1 diabetes. J Autoimmun 2007; 28: 134-42 .
140. Kojima H, Nakamura T, Fujita Y, et al. Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 2002; 51: 1398-408 .
141. Han J, Lee HH, Kwon H, Shin S, Yoon JW, Jun HS. Engineered enteroendocrine cells secrete insulin in response to glucose and reverse hyperglycemia in diabetic mice. Mol Ther 2007; 15: 1195-202 .
142. Choi D, Lee HJ, Jee S, et al. In vitro differentiation of mouse embryonic stem cells: enrichment of endodermal cells in the embryoid body. Stem Cells 2005;23:817-27