Abstract
Type 1 diabetes mellitus (T1DM) is a disease that results from the selective autoimmune
destruction of insulin-producing β-cells. This disease process lends itself to cellular
therapy because of the single cell nature of insulin production. Murine models have
provided opportunities for the study of cellular therapies for the treatment of diabetes,
including the investigation of islet transplantation, and also the possibility of
stem cell therapies and islet regeneration. Studies in islet transplantation have
included both allo- and xeno-transplantation and have allowed for the study of new
approaches for the reversal of autoimmunity and achieving immune tolerance. Stem cells
from hematopoietic sources such as bone marrow and fetal cord blood, as well as from
the pancreas, intestine, liver, and spleen promise either new sources of islets or
may function as stimulators of islet regeneration. This review will summarize the
various cellular interventions investigated as potential treatments of T1DM.
Key words
type 1 diabetes mellitus - islet transplantation - β-cells - stem cell therapy
References
- 1
Sheehy MJ, Scharf SJ, Rowe JR, Neme de Gimenez MH, Meske LM, Erlich HA, Nepom BS.
A diabetes-susceptible HLA haplotype is best defined by a combination of HLA-DR and
-DQ alleles.
J Clin Invest.
1989;
83
830-835
- 2
Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA.
Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize
an insulin epitope.
Nature.
2005;
435
224-228
- 3
Eisenbarth GS, Gottlieb PA.
Autoimmune polyendocrine syndromes.
N Engl J Med.
2004;
350
2068-2079
- 4
Jahromi MM, Eisenbarth GS.
Cellular and molecular pathogenesis of type 1A diabetes.
Cell Mol Life Sci.
2007;
64
865-872
- 5
Stehouwer CD, Lambert J, Donker AJ, Hinsbergh VW van.
Endothelial dysfunction and pathogenesis of diabetic angiopathy.
Cardiovasc Res.
1997;
34
55-68
- 6
Barr CC.
Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial
of intensive insulin therapy, by The Diabetes Control and Complications Trial/Epidemiology
of Diabetes Interventions and Complications Research Group.
N Engl J Med.
2001;
342
381-389
- 7
Zhang L, Krzentowski G, Albert A, Lefebvre PJ.
Risk of developing retinopathy in diabetes control and Complications Trial type 1
diabetic patients with good or poor metabolic control.
Diabetes Care.
2001;
24
1275-1279
- 8
Rother KI, Harlan DM.
Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus.
J Clin Invest.
2004;
114
877-883
- 9
Anderson MS, Bluestone JA.
The NOD mouse: a model of immune dysregulation.
Annu Rev Immunol.
2005;
23
447-485
- 10
Tochino Y.
The NOD mouse as a model of type I diabetes.
Crit Rev Immunol.
1987;
8
49-81
- 11
Hutton JC, Eisenbarth GS.
A pancreatic beta-cell-specific homolog of glucose-6-phosphatase emerges as a major
target of cell-mediated autoimmunity in diabetes.
Proc Natl Acad Sci USA.
2003;
100
8626-8628
- 12
Lieberman SM, Evans AM, Han B, Takaki T, Vinnitskaya Y, Caldwell JA, Serreze DV, Shabanowitz J,
Hunt DF, Nathenson SG, Santamaria P, DiLorenzo TP.
Identification of the beta cell antigen targeted by a prevalent population of pathogenic
CD8+ T cells in autoimmune diabetes.
Proc Natl Acad Sci USA.
2003;
100
8384-8388
- 13
Like AA, Appel MC, Williams RM, Rossini AA.
Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies.
Lab Invest.
1978;
38
470-486
- 14
Rossini AA, Like AA, Chick WL, Appel MC, Cahill Jr GF.
Studies of streptozotocin-induced insulitis and diabetes.
Proc Natl Acad Sci USA.
1977;
74
2485-2489
- 15
MacEvoy RC, Andersson J, Sandler S, Hellerstrom C.
Multiple low-dose streptozotocin-induced diabetes in the mouse. Evidence for stimulation
of a cytotoxic cellular immune response against an insulin-producing beta cell line.
J Clin Invest.
1984;
74
715-722
- 16
Ballinger WF, Lacy PE.
Transplantation of intact pancreatic islets in rats.
Surgery.
1972;
72
175-186
- 17
Mullen Y, Maruyama M, Smith CV.
Current progress and perspectives in immunoisolated islet transplantation.
J Hepatobiliary Pancreat Surg.
2000;
7
347-357
- 18
Yonekawa Y, Okitsu T, Wake K, Iwanaga Y, Noguchi H, Nagata H, Liu X, Kobayashi N,
Matsumoto S.
A new mouse model for intraportal islet transplantation with limited hepatic lobe
as a graft site.
Transplantation.
2006;
82
712-715
- 19
Brendel MD, Hering B, Schultz AO. et al .
International Islet Transplant Registry.
Newsletter.
2001;
8
4
- 20 Bretzel RG, Hering BJ, Stroedter D. et al .Experimental islet transplantation in
small animals. In Pancreatic Islet Cell Transplantation. Ricordi RG (ed) Landes Company,
Austin 1992: 250
- 21
Juang JH, Hsu BR, Kuo CH.
Islet transplantation at subcutaneous and intramuscular sites.
Transplant Proc.
2005;
37
3479-3481
- 22
Rood PP, Bottino R, Balamurugan AN, Fan Y, Cooper DK, Trucco M.
Facilitating physiologic self-regeneration: a step beyond islet cell replacement.
Pharm Res.
2006;
23
227-242
- 23
Chong AS, Shen J, Tao J, Yin D, Kuznetsov A, Hara M, Philipson LH.
Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell
regeneration.
Science.
2006;
311
1774-1775
- 24
Yin D, Tao J, Lee DD, Shen J, Hara M, Lopez J, Kuznetsov A, Philipson LH, Chong AS.
Recovery of islet beta-cell function in streptozotocin- induced diabetic mice: an
indirect role for the spleen.
Diabetes.
2006;
55
3256-3263
- 25
Witkowski P, Zakai SB, Rana A, Sledzinski Z, Hardy MA.
Pancreatic islet transplantation, what has been achieved since Edmonton break-through.
Ann Transplant.
2006;
11
5-13
, ; discussion 32-43
- 26
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
- 27
Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A,
Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B,
Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE,
Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V,
Bluestone J, Lakey JR.
International trial of the Edmonton protocol for islet transplantation.
N Engl J Med.
2006;
355
1318-1330
- 28
Bennet W, Groth CG, Larsson R, Nilsson B, Korsgren O.
Isolated human islets trigger an instant blood mediated inflammatory reaction: implications
for intraportal islet transplantation as a treatment for patients with type 1 diabetes.
Ups J Med Sci.
2000;
105
125-133
- 29
Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R, Ostraat O, Salmela K,
Tibell A, Tufveson G, Elgue G, Nilsson Ekdahl K, Korsgren O, Nilsson B.
Production of tissue factor by pancreatic islet cells as a trigger of detrimental
thrombotic reactions in clinical islet transplantation.
Lancet.
2002;
360
2039-2045
- 30
Yin D, Ding JW, Shen J, Ma L, Hara M, Chong AS.
Liver ischemia contributes to early islet failure following intraportal transplantation:
benefits of liver ischemic-preconditioning.
Am J Transplant.
2006;
6
60-68
- 31
Markmann JF, Rosen M, Siegelman ES, Soulen MC, Deng S, Barker CF, Naji A.
Magnetic resonance-defined periportal steatosis following intraportal islet transplantation:
a functional footprint of islet graft survival?.
Diabetes.
2003;
52
1591-1594
- 32
Gupta V, Wahoff DC, Rooney DP, Poitout V, Sutherland DE, Kendall DM, Robertson RP.
The defective glucagon response from transplanted intrahepatic pancreatic islets during
hypoglycemia is transplantation site-determined.
Diabetes.
1997;
46
28-33
- 33
Al-Abdullah IH, Anil Kumar MS, Kelly-Sullivan D, Abouna GM.
Site for unpurified islet transplantation is an important parameter for determination
of the outcome of graft survival and function.
Cell Transplant.
1995;
4
297-305
- 34
Gustavson SM, Rajotte RV, Hunkeler D, Lakey JR, Edgerton DS, Neal DW, Snead WL, Penaloza AR,
Cherrington AD.
Islet auto-transplantation into an omental or splenic site results in a normal beta
cell but abnormal alpha cell response to mild non-insulin-induced hypoglycemia.
Am J Transplant.
2005;
5
2368-2377
- 35
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
- 36
Braghi S, Bonifacio E, Secchi A, Carlo V Di, Pozza G, Bosi E.
Modulation of humoral islet autoimmunity by pancreas allotransplantation influences
allograft outcome in patients with type 1 diabetes.
Diabetes.
2000;
49
218-224
- 37
Jaeger C, Brendel MD, Hering BJ, Eckhard M, Bretzel RG.
Progressive islet graft failure occurs significantly earlier in autoantibody-positive
than in autoantibody-negative IDDM recipients of intrahepatic islet allografts.
Diabetes.
1997;
46
1907-1910
- 38
Okitsu T, Bartlett ST, Hadley GA, Drachenberg CB, Farney AC.
Recurrent autoimmunity accelerates destruction of minor and major histoincompatible
islet grafts in nonobese diabetic [NOD] mice.
Am J Transplant.
2001;
1
138-145
- 39
Ming CS, Chen ZH.
Progress in pancreas transplantation and combined pancreas-kidney transplantation.
Hepatobiliary Pancreat Dis Int.
2007;
6
17-23
- 40
Paty BW, Harmon JS, Marsh CL, Robertson RP.
Inhibitory effects of immunosuppressive drugs on insulin secretion from HIT-T15 cells
and Wistar rat islets.
Transplantation.
2002;
73
353-357
- 41
Kirchhof N, Shibata S, Wijkstrom M, Kulick DM, Salerno CT, Clemmings SM, Heremans Y,
Galili U, Sutherland DE, Dalmasso AP, Hering BJ.
Reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine
islet xenografts precedes acute cellular rejection.
Xenotransplantation.
2004;
11
396-407
- 42
Wijkstrom M, Kenyon NS, Kirchhof N, Kenyon NM, Mullon C, Lake P, Cottens S, Ricordi C,
Hering BJ.
Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD,
and FTY720.
Transplantation.
2004;
77
827-835
- 43
Berney T, Pileggi A, Molano RD, Poggioli R, Zahr E, Ricordi C, Inverardi L.
The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic
islet grafts in nonobese diabetic mice.
Transplantation.
2003;
76
1669-1674
- 44
Ferrari-Lacraz S, Zheng XX, Kim YS, Li Y, Maslinski W, Li XC, Strom TB.
An antagonist IL-15/Fc protein prevents costimulation blockade-resistant rejection.
J Immunol.
2001;
167
3478-3485
- 45
Kenyon NS, Chatzipetrou M, Masetti M, Ranuncoli A, Oliveira M, Wagner JL, Kirk AD,
Harlan DM, Burkly LC, Ricordi C.
Long-term survival and function of intrahepatic islet allografts in rhesus monkeys
treated with humanized anti-CD154.
Proc Natl Acad Sci USA.
1999;
96
8132-8137
- 46
Kenyon NS, Fernandez LA, Lehmann R, Masetti M, Ranuncoli A, Chatzipetrou M, Iaria G,
Han D, Wagner JL, Ruiz P, Berho M, Inverardi L, Alejandro R, Mintz DH, Kirk AD, Harlan DM,
Burkly LC, Ricordi C.
Long-term survival and function of intrahepatic islet allografts in baboons treated
with humanized anti-CD154.
Diabetes.
1999;
48
1473-1481
- 47
Koulmanda M, Smith RN, Qipo A, Weir G, Auchincloss H, Strom TB.
Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based
therapy: nonimmunologic graft failure?.
Am J Transplant.
2006;
6
687-696
- 48
Rayat GR, Gill RG.
Indefinite survival of neonatal porcine islet xenografts by simultaneous targeting
of LFA-1 and CD154 or CD45RB.
Diabetes.
2005;
54
443-451
- 49
Street CN, Sipione S, Helms L, Binette T, Rajotte RV, Bleackley RC, Korbutt GS.
Stem cell-based approaches to solving the problem of tissue supply for islet transplantation
in type 1 diabetes.
Int J Biochem Cell Biol.
2004;
36
667-683
- 50
Lu P, Liu F, Yan L, Peng T, Liu T, Yao Z, Wang CY.
Stem cells therapy for type 1 diabetes.
Diabetes Res Clin Pract.
2007;
, in press
- 51
MadsenOD, Jensen J, Blume N, Petersen HV, Lund K, Karlsen C, Andersen FG, Jensen PB,
Larsson LI, Serup P.
Pancreatic development and maturation of the islet B cell. Studies of pluripotent
islet cultures.
Eur J Biochem.
1996;
242
435-445
- 52
Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG.
Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic
stem cells.
Nat Med.
2000;
6
278-282
- 53
Dudek RW, Lawrence Jr IE, Hill RS, Johnson RC.
Induction of islet cytodifferentiation by fetal mesenchyme in adult pancreatic ductal
epithelium.
Diabetes.
1991;
40
1041-1048
- 54
Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O’Neil JJ.
In vitro cultivation of human islets from expanded ductal tissue.
Proc Natl Acad Sci USA.
2000;
97
7999-8004
- 55
Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller 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
- 56
Abraham EJ, Leech CA, Lin JC, Zulewski H, Habener JF.
Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic
islet-derived progenitor cells into insulin-producing cells.
Endocrinology.
2002;
143
3152-3161
- 57
Ogata T, Park KY, Seno M, Kojima I.
Reversal of streptozotocin-induced hyperglycemia by transplantation of pseudoislets
consisting of beta cells derived from ductal cells.
Endocr J.
2004;
51
381-386
- 58
Hao E, Tyrberg B, Itkin-Ansari P, Lakey JR, Geron I, Monosov EZ, Barcova M, Mercola M,
Levine F.
Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas.
Nat Med.
2006;
12
310-316
- 59
Dor Y, Brown J, Martinez OI, Melton DA.
Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
Nature.
2004;
429
41-46
- 60
Brennand K, Huangfu D, Melton D.
All beta cells contribute equally to islet growth and maintenance.
PLoS Biol.
2007;
5
e163
- 61
Bonner-Weir S, Sharma A.
Are there pancreatic progenitor cells from which new islets form after birth?.
Nat Clin Pract Endocrinol Metab.
2006;
2
240-241
- 62
Zaret KS.
Liver specification and early morphogenesis.
Mech Dev.
2000;
92
83-88
- 63
Suzuki A, Zheng YW, Kaneko S, Onodera M, Fukao K, Nakauchi H, Taniguchi H.
Clonal identification and characterization of self-renewing pluripotent stem cells
in the developing liver.
J Cell Biol.
2002;
156
173-184
- 64
Yang LJ.
Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes.
Autoimmun Rev.
2006;
5
409-413
- 65
Yang L, Li S, Hatch H, Ahrens K, Cornelius JG, Petersen BE, Peck AB.
In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine
hormone-producing cells.
Proc Natl Acad Sci USA.
2002;
99
8078-8083
- 66
Zalzman M, Gupta S, Giri RK, Berkovich I, Sappal BS, Karnieli O, Zern MA, Fleischer N,
Efrat S.
Reversal of hyperglycemia in mice by using human expandable insulin-producing cells
differentiated from fetal liver progenitor cells.
Proc Natl Acad Sci USA.
2003;
100
7253-7258
- 67
Ryu S, Kodama S, Ryu K, Schoenfeld DA, Faustman DL.
Reversal of established autoimmune diabetes by restoration of endogenous beta cell
function.
J Clin Invest.
2001;
108
63-72
- 68
Kodama S, Kuhtreiber W, Fujimura S, Dale EA, Faustman DL.
Islet regeneration during the reversal of autoimmune diabetes in NOD mice.
Science.
2003;
302
1223-1227
- 69
Faustman DL, Tran SD, Kodama S, Lodde BM, Szalayova I, Key S, Toth ZE, Mezey E.
Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal
in NOD mice.
Science.
2006;
314
1243
, ; authors' reply 1243
- 70
Suri A, Calderon B, Esparza TJ, Frederick K, Bittner P, Unanue ER.
Immunological reversal of autoimmune diabetes without hematopoietic replacement of
beta cells.
Science.
2006;
311
1778-1780
- 71
Nishio J, Gaglia JL, Turvey SE, Campbell C, Benoist C, Mathis D.
Islet recovery and reversal of murine type 1 diabetes in the absence of any infused
spleen cell contribution.
Science.
2006;
311
1775-1778
- 72
Cheung AT, Dayanandan B, Lewis JT, Korbutt GS, Rajotte RV, Bryer-Ash M, Boylan MO,
Wolfe MM, Kieffer TJ.
Glucose-dependent insulin release from genetically engineered K cells.
Science.
2000;
290
1959-1962
- 73
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
1195-1202
- 74
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
843-850
- 75
Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE.
Adult bone marrow-derived cells trans-differentiating into insulin-producing cells
for the treatment of type I diabetes.
Lab Invest.
2004;
84
607-617
- 76
Moriscot C, Fraipont F de, 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
- 77
Sun Y, Chen L, Hou XG, Hou WK, Dong JJ, Sun L, Tang KX, Wang B, Song J, Li H, Wang KX.
Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients
into insulin-producing cells in vitro.
Chin Med J [Engl].
2007;
120
771-776
- 78
Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ.
In vivo and in vitro characterization of insulin-producing cells obtained from murine
bone marrow.
Diabetes.
2004;
53
1721-1732
- 79
Kang EM, Zickler PP, Burns S, Langemeijer SM, Brenner S, Phang OA, Patterson N, Harlan D,
Tisdale JF.
Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not
contribute to significant islet cell regeneration once disease is established.
Exp Hematol.
2005;
33
699-705
- 80
Mathews V, Hanson PT, Ford E, Fujita J, Polonsky KS, Graubert TA.
Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta-cell
injury.
Diabetes.
2004;
53
91-98
- 81
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
- 82
Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, Thyssen S, Gray DA, Bhatia M.
Bone marrow-derived stem cells initiate pancreatic regeneration.
Nat Biotechnol.
2003;
21
763-770
- 83
Hasegawa Y, Ogihara T, Yamada T, Ishigaki Y, Imai J, Uno K, Gao J, Kaneko K, Ishihara H,
Sasano H, Nakauchi H, Oka Y, Katagiri H.
Bone marrow [BM] transplantation promotes beta-cell regeneration after acute injury
through BM cell mobilization.
Endocrinology.
2007;
148
2006-2015
- 84
Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ.
Multipotent stromal cells from human marrow home to and promote repair of pancreatic
islets and renal glomeruli in diabetic NOD/scid mice.
Proc Natl Acad Sci USA.
2006;
103
17438-17443
- 85
Zorina TD, Subbotin VM, Bertera S, Alexander AM, Haluszczak C, Gambrell B, Bottino R,
Styche AJ, Trucco M.
Recovery of the endogenous beta cell function in the NOD model of autoimmune diabetes.
Stem Cells.
2003;
21
377-388
- 86
Steptoe RJ, Ritchie JM, Harrison LC.
Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes.
J Clin Invest.
2003;
111
1357-1363
- 87
Kogler G, Sensken S, Airey JA, Trapp T, Muschen M, Feldhahn N, Liedtke S, Sorg RV,
Fischer J, Rosenbaum C, Greschat S, Knipper A, Bender J, Degistirici O, Gao J, Caplan AI,
Colletti EJ, Almeida-Porada G, Muller HW, Zanjani E, Wernet P.
A new human somatic stem cell from placental cord blood with intrinsic pluripotent
differentiation potential.
J Exp Med.
2004;
200
123-135
- 88
Koblas T, Harman SM, Saudek F.
The application of umbilical cord blood cells in the treatment of diabetes mellitus.
Rev Diabet Stud.
2005;
2
228-234
- 89
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
- 90
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
- 91
Ende N, Chen R, Reddi AS.
Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic
mice.
Biochem Biophys Res Commun.
2004;
325
665-669
- 92
Ende N, Chen R, Reddi AS.
Transplantation of human umbilical cord blood cells improves glycemia and glomerular
hypertrophy in type 2 diabetic mice.
Biochem Biophys Res Commun.
2004;
321
168-171
- 93
Yoshida S, Ishikawa F, Kawano N, Shimoda K, Nagafuchi S, Shimoda S, Yasukawa M, Kanemaru T,
Ishibashi H, Shultz LD, Harada M.
Human cord blood-derived cells generate insulin-producing cells in vivo.
Stem Cells.
2005;
23
1409-1416
- 94
Blyszczuk P, Wobus AM.
In vitro differentiation of embryonic stem cells into the pancreatic lineage.
Methods Mol Biol.
2006;
330
373-385
- 95
Marenah L, MacCluskey JT, Abdel-Wahab YH, O’Harte FP, MacClenaghan NH, Flatt PR.
A stable analogue of glucose-dependent insulinotropic polypeptide, GIP[LysPAL16],
enhances functional differentiation of mouse embryonic stem cells into cells expressing
islet-specific genes and hormones.
Biol Chem.
2006;
387
941-947
- 96
Brolen GK, Heins N, Edsbagge J, Semb H.
Signals from the embryonic mouse pancreas induce differentiation of human embryonic
stem cells into insulin-producing beta-cell-like cells.
Diabetes.
2005;
54
2867-2874
- 97
Soria B, Roche E, Berna 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
157-162
- 98
Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, MacKay R.
Differentiation of embryonic stem cells to insulin-secreting structures similar to
pancreatic islets.
Science.
2001;
292
1389-1394
- 99
Schroeder IS, Rolletschek A, Blyszczuk P, Kania G, Wobus AM.
Differentiation of mouse embryonic stem cells to insulin-producing cells.
Nat Protoc.
2006;
1
495-507
- 100
Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA.
Insulin staining of ES cell progeny from insulin uptake.
Science.
2003;
299
363
- 101
Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Hakansson J,
Fleckner J, Skold HN, Melton D, Semb H, Serup P.
Artifactual insulin release from differentiated embryonic stem cells.
Diabetes.
2004;
53
2603-2609
- 102
Milne HM, Burns CJ, Kitsou-Mylona I, Luther MJ, Minger SL, Persaud SJ, Jones PM.
Generation of insulin-expressing cells from mouse embryonic stem cells.
Biochem Biophys Res Commun.
2005;
328
399-403
- 103
Evans MJ, Kaufman MH.
Establishment in culture of pluripotential cells from mouse embryos.
Nature.
1981;
292
154-156
- 104
Grinnemo KH, Kumagai-Braesch M, Mansson-Broberg A, Skottman H, Hao X, Siddiqui A,
Andersson A, Stromberg AM, Lahesmaa R, Hovatta O, Sylven C, Corbascio M, Dellgren G.
Human embryonic stem cells are immunogenic in allogeneic and xenogeneic settings.
Reprod Biomed Online.
2006;
13
712-724
- 105
Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, Lebl DR, Caffarelli AD,
Bruin JL de, Fedoseyeva EV, Robbins RC.
Embryonic stem cell immunogenicity increases upon differentiation after transplantation
into ischemic myocardium.
Circulation.
2005;
112
I166-I172
Correspondence
A.S. Chong
University of Chicago
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