Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: Phase I/II clinical trial

BMC Medicine

Volumn 11, Issue 1, 2013, Pages

  Zhao, Yong ^a,b   Jiang, Zhaoshun ^c   Zhao, Tingbao ^c   Ye, Mingliang ^c   Hu, Chengjin ^c   Zhou, Huimin ^d   Yin, Zhaohui ^c   Chen, Yana ^e   Zhang, Ye ^b   Wang, Shanfeng ^b   Shen, Jie ^b   Thaker, Hatim ^a   Jain, Summit ^a   Li, Yunxiang ^b   Diao, Yalin ^c   Chen, Yingjian ^c   Sun, Xiaoming ^c   Fisk, Mary Beth ^f   Li, Heng ^e  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b Jinan Tianhe Stem Cell Biotechology Co Ltd   (China)

^c JINAN MILITARY GENERAL HOSPITAL   (China)

^d HEBEI MEDICAL UNIVERSITY   (China)

^e SHANDONG UNIVERSITY   (China)

^f Texas Cord Blood Bank   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

C PEPTIDE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; ORAL ANTIDIABETIC AGENT;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DIET; EXERCISE; FEMALE; FOLLOW UP; GLUCOSE BLOOD LEVEL; HUMAN; IMMUNOMODULATION; INFLAMMATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; INSULIN TREATMENT; MALE; MEASUREMENT; METABOLIC REGULATION; MONONUCLEAR CELL; MULTIPOTENT STEM CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PANCREAS ISLET BETA CELL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; SAFETY; STEM CELL EDUCATOR THERAPY; STEM CELL TRANSPLANTATION; UMBILICAL CORD BLOOD;

ADULT; AGED; COCULTURE TECHNIQUES; DIABETES MELLITUS, TYPE 2; FEMALE; FETAL BLOOD; FOLLOW-UP STUDIES; HUMANS; HYPOGLYCEMIC AGENTS; IMMUNOMODULATION; INSULIN RESISTANCE; MALE; MIDDLE AGED; MOLECULAR TARGETED THERAPY; MULTIPOTENT STEM CELLS; STEM CELL TRANSPLANTATION; TRANSPLANTATION, AUTOLOGOUS;

EID: 84880030508     PISSN: None     EISSN: 17417015     Source Type: Journal    
DOI: 10.1186/1741-7015-11-160     Document Type: Article

References (67)

1. Diamond J. Medicine: diabetes in India. Nature 2011, 469:478-479. 10.1038/469478a, 21270882.
2. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J, China National Diabetes and Metabolic Disorders Study Group Prevalence of diabetes among men and women in China. N Engl J Med 2010, 362:1090-1101. 10.1056/NEJMoa0908292, 20335585, China National Diabetes and Metabolic Disorders Study Group.
3. Zhao Y, Jiang Z, Guo C. New hope for type 2 diabetics: Targeting insulin resistance through the immune modulation of stem cells. Autoimmun Rev 2011, 11:137-142. 10.1016/j.autrev.2011.09.003, 21964164.
4. Loke YK, Kwok CS, Singh S. Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. BMJ 2011, 342:d1309. 10.1136/bmj.d1309, 3230110, 21415101.
5. Stephenson J. Diabetes drug may be associated with increase in risk of bladder cancer. JAMA 2011, 306:143. 10.1001/jama.2011.939, 21750286.
6. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010, 72:219-246. 10.1146/annurev-physiol-021909-135846, 20148674.
7. Schenk S, Saberi M, Olefsky JM. Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 2008, 118:2992-3002. 10.1172/JCI34260, 2522344, 18769626.
8. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006, 116:1793-1801. 10.1172/JCI29069, 1483173, 16823477.
9. Winer S, Paltser G, Chan Y, Tsui H, Engleman E, Winer D, Dosch HM. Obesity predisposes to Th17 bias. Eur J Immunol 2009, 39:2629-2635. 10.1002/eji.200838893, 19662632.
10. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011, 11:98-107. 10.1038/nri2925, 21233852.
11. Couzin-Frankel J. Trying to reset the clock on type 1 diabetes. Science 2011, 333:819-821. 10.1126/science.333.6044.819, 21835995.
12. Bach JF. Anti-CD3 antibodies for type 1 diabetes: beyond expectations. Lancet 2011, 378:459-460. 10.1016/S0140-6736(11)60980-X, 21719098.
13. Mathieu C, Gillard P. Arresting type 1 diabetes after diagnosis: GAD is not enough. Lancet 2011, 378:291-292. 10.1016/S0140-6736(11)60978-1, 21715000.
14. Zhao Y, Wang H, Mazzone T. Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Exp Cell Res 2006, 312:2454-2464. 10.1016/j.yexcr.2006.04.008, 16716296.
15. Zhao Y, Huang Z, Qi M, Lazzarini P, Mazzone T. Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell. Immunol Lett 2007, 108:78-87. 10.1016/j.imlet.2006.10.007, 17161871.
16. Zhao Y, Lin B, Darflinger R, Zhang Y, Holterman MJ, Skidgel RA. Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice. PLoS One 2009, 4:e4226. 10.1371/journal.pone.0004226, 2627485, 19156219.
17. Zhao Y, Mazzone T. Human cord blood stem cells and the journey to a cure for type 1 diabetes. Autoimmun Rev 2010, 10:103-107. 10.1016/j.autrev.2010.08.011, 20728583.
18. Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med 2012, 10:3. 10.1186/1741-7015-10-3, 3322343, 22233865.
19. Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep 2012, 12:517-523. 10.1007/s11892-012-0308-1, 22833322.
20. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008, 294:E15-E26.
21. Radaelli T, Farrell KA, Huston-Presley L, Amini SB, Kirwan JP, McIntyre HD, Catalano PM. Estimates of insulin sensitivity using glucose and C-Peptide from the hyperglycemia and adverse pregnancy outcome glucose tolerance test. Diabetes Care 2010, 33:490-494. 10.2337/dc09-1463, 2827494, 20032280.
22. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419. 10.1007/BF00280883, 3899825.
23. Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005, 352:2598-2608. 10.1056/NEJMoa043980, 15972866.
24. Ludvigsson J, Faresjö M, Hjorth M, Axelsson S, Chéramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson NO, Aman J, Ortqvist E, Zerhouni P, Casas R. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 2008, 359:1909-1920. 10.1056/NEJMoa0804328, 18843118.
25. Zhao Y, Mazzone T. Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion. Exp Cell Res 2005, 310:311-318. 10.1016/j.yexcr.2005.08.004, 16143325.
26. Devaraj S, Dasu MR, Jialal I. Diabetes is a proinflammatory state: a translational perspective. Expert Rev Endocrinol Metab 2010, 5:19-28. 10.1586/eem.09.44, 2829992, 20204165.
27. Devaraj S, Jialal I. Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation. Circulation 2000, 102:191-196. 10.1161/01.CIR.102.2.191, 10889130.
28. Brooks-Worrell B, Palmer JP. Is diabetes mellitus a continuous spectrum?. Clin Chem 2011, 57:158-161. 10.1373/clinchem.2010.148270, 21068340.
29. Brooks-Worrell BM, Reichow JL, Goel A, Ismail H, Palmer JP. Identification of autoantibody-negative autoimmune type 2 diabetic patients. Diabetes Care 2011, 34:168-173. 10.2337/dc10-0579, 3004952, 20855551.
30. Goldfine AB, Fonseca V, Shoelson SE. Therapeutic approaches to target inflammation in type 2 diabetes. Clin Chem 2011, 57:162-167. 10.1373/clinchem.2010.148833, 3227024, 21098138.
31. Mathis D, Shoelson SE. Immunometabolism: an emerging frontier. Nat Rev Immunol 2011, 11:81. 10.1038/nri2922, 21469396.
32. Naik RG, Palmer JP. Latent autoimmune diabetes in adults (LADA). Rev Endocr Metab Disord 2003, 4:233-241. 10.1023/A:1025148211587, 14501174.
33. Jagannathan-Bogdan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, Nikolajczyk BS. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol 2011, 186:1162-1172. 10.4049/jimmunol.1002615, 3089774, 21169542.
34. Sumarac-Dumanovic M, Stevanovic D, Ljubic A, Jorga J, Simic M, Stamenkovic-Pejkovic D, Starcevic V, Trajkovic V, Micic D. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes (Lond) 2009, 33:151-156.
35. Wu HP, Kuo SF, Wu SY, Chuang DY. High interleukin-12 production from stimulated peripheral blood mononuclear cells of type 2 diabetes patients. Cytokine 2010, 51:298-304. 10.1016/j.cyto.2010.06.014, 20634089.
36. Mishra M, Kumar H, Bajpai S, Singh RK, Tripathi K. Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2 diabetes. Diabetes Res Clin Pract 2011, 94:255-261. 10.1016/j.diabres.2011.07.037, 21855158.
37. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 2012, 18:363-374. 10.1038/nm.2627, 22395709.
38. Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T. Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia 2012, 55:2583-2592. 10.1007/s00125-012-2607-0, 22733483.
39. Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab 2012, 15:635-645. 10.1016/j.cmet.2012.04.001, 22560216.
40. Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol 2012, 8:709-716. 10.1038/nrendo.2012.114, 22847239.
41. Beug ST, Cheung HH, Lacasse EC, Korneluk RG. Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol 2012, 33:535-545. 10.1016/j.it.2012.06.004, 22836014.
42. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011, 378:169-181. 10.1016/S0140-6736(11)60614-4, 21705072.
43. Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008, 34:2-11. 10.1016/j.diabet.2007.09.004, 18093861.
44. Bhargava P, Lee CH. Role and function of macrophages in the metabolic syndrome. Biochem J 2012, 442:253-262. 10.1042/BJ20111708, 22329799.
45. Rajwani A, Cubbon RM, Wheatcroft SB. Cell-specific insulin resistance: implications for atherosclerosis. Diabetes Metab Res Rev 2012, 28:627-634. 10.1002/dmrr.2336, 22987644.
46. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006, 116:1494-1505. 10.1172/JCI26498, 1459069, 16691291.
47. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M, Yamauchi T, Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Nagai R, Kadowaki T. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 2006, 281:26602-26614. 10.1074/jbc.M601284200, 16809344.
48. Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 2008, 8:301-309. 10.1016/j.cmet.2008.08.015, 2630775, 18840360.
49. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005, 23:515-548. 10.1146/annurev.immunol.23.021704.115611, 15771580.
50. Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004, 4:336-347. 10.1038/nri1349, 15122199.
51. Sethna MP, Van Parijs L, Sharpe AH, Abbas AK, Freeman GJ. A negative regulatory function of B7 revealed in B7-1 transgenic mice. Immunity 1994, 1:415-421. 10.1016/1074-7613(94)90072-8, 7533646.
52. Bugeon L, Dallman MJ. Costimulation of T cells. Am J Respir Crit Care Med 2000, 162:S164-S168. 10.1164/ajrccm.162.supplement_3.15tac5, 11029388.
53. Defuria J, Belkina AC, Jagannathan-Bogdan M, Snyder-Cappione J, Carr JD, Nersesova YR, Markham D, Strissel KJ, Watkins AA, Zhu M, Allen J, Bouchard J, Toraldo G, Jasuja R, Obin MS, McDonnell ME, Apovian C, Denis GV, Nikolajczyk BS. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A 2013, 110:5133-5138. 10.1073/pnas.1215840110, 23479618.
54. Haskell BD, Flurkey K, Duffy TM, Sargent EE, Leiter EH. The diabetes-prone NZO/HlLt strain. I. Immunophenotypic comparison to the related NZB/BlNJ and NZW/LacJ strains. Lab Invest 2002, 82:833-842.
55. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 2011, 17:610-617. 10.1038/nm.2353, 3270885, 21499269.
56. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 2009, 15:921-929. 10.1038/nm.2001, 3063199, 19633657.
57. Winer S, Winer DA. The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance. Immunol Cell Biol 2012, 90:755-762. 10.1038/icb.2011.110, 22231651.
58. Talukdar S, da Oh Y, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 2012, 18:1407-1412. 10.1038/nm.2885, 3491143, 22863787.
59. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011, 332:243-247. 10.1126/science.1201475, 3144160, 21436399.
60. Liu J, Divoux A, Sun J, Zhang J, Clement K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Shi GP. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 2009, 15:940-945. 10.1038/nm.1994, 2736875, 19633655.
61. Musilli C, Paccosi S, Pala L, Gerlini G, Ledda F, Mugelli A, Rotella CM, Parenti A. Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients. Mol Immunol 2011, 49:234-238. 10.1016/j.molimm.2011.08.019, 21940050.
62. Zhong J, Rao X, Deiuliis J, Braunstein Z, Narula V, Hazey J, Mikami D, Needleman B, Satoskar AR, Rajagopalan S. A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation. Diabetes 2013, 62:149-157. 10.2337/db12-0230, 22936179.
63. Kohn LD, Wallace B, Schwartz F, McCall K. Is type 2 diabetes an autoimmune-inflammatory disorder of the innate immune system?. Endocrinology 2005, 146:4189-4191. 10.1210/en.2005-0920, 16166230.
64. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 2006, 24:99-146. 10.1146/annurev.immunol.24.021605.090737, 16551245.
65. Li MO, Flavell RA. TGF-beta: a master of all T cell trades. Cell 2008, 134:392-404. 10.1016/j.cell.2008.07.025, 3677783, 18692464.
66. Zhao Y, Lin B, Dingeldein M, Guo C, Hwang D, Holterman MJ. New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes. Transl Res 2010, 155:211-216. 10.1016/j.trsl.2010.01.003, 20403575.
67. Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, Tesselaar K, Koenderman L. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood 2010, 116:625-627. 10.1182/blood-2010-01-259028, 20410504.