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Diabetes-associated macrovascular complications: cell-based therapy a new tool?

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Abstract

Diabetes mellitus and its ongoing macrovascular complications represent one of the major health problems around the world. Rise in obesity and population ages correlate with the increased incidence of diabetes. This highlights the need for novel approaches to prevent and treat this pandemic. The discovery of a reservoir of stem/progenitors in bone marrow and in mesenchymal tissue has attracted interest of both biologists and clinicians. A number of preclinical and clinical trials were developed to explore their potential clinical impact, as target or vehicle, in different clinical settings, including diabetes complications. Currently, bone marrow, peripheral blood, mesenchymal, and adipose tissues have been used as stem/progenitor cell sources. However, evidences have been provided that both bone marrow and circulating progenitor cells are dysfunctional in diabetes. These observations along with the growing advantages in genetic manipulation have spurred researchers to exploit ex vivo manipulated cells to overcome these hurdles. In this article, we provide an overview of data relevant to stem-progenitors potential clinical application in revascularization and/or vascular repair. Moreover, the hurdles at using progenitor cells in diabetic patients will be also discussed.

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References

  1. F. Ismail-Beigi, Clinical practice. Glycemic management of type 2 diabetes mellitus. N. Engl. J. Med. 366, 1319–1327 (2012)

    PubMed  CAS  Google Scholar 

  2. N. Chaturvedi, The burden of diabetes and its complications: trends and implications for intervention. Diabetes Res. Clin. Pract. 76, S3–S12 (2007)

    PubMed  Google Scholar 

  3. P. Patel, A. Macerollo, Diabetes mellitus: diagnosis and screening. Am. Fam. Physician 81, 863–870 (2010)

    PubMed  Google Scholar 

  4. S. Keymel, Y. Heinen, J. Balzer, T. Rassaf, M. Kelm, T. Lauer, C. Heiss, Characterization of macro-and microvascular function and structure in patients with type 2 diabetes mellitus. Am. J. Cardiovasc. Dis. 1, 68–75 (2011)

    PubMed  CAS  Google Scholar 

  5. S.M. Marshall, A. Flyvbjerg, Prevention and early detection of vascular complications of diabetes. BMJ 333, 475–480 (2006)

    PubMed  Google Scholar 

  6. A.R. Pries, B. Reglin, T.W. Secomb, Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli. Hypertension 46, 725–731 (2005)

    PubMed  CAS  Google Scholar 

  7. A.M. Heagerty, C. Aalkjaer, S.J. Bund, N. Korsgaard, M.J. Mulvany, Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension 21, 391–397 (1993)

    PubMed  CAS  Google Scholar 

  8. D.M. Nathan, P.A. Cleary, J.Y. Backlund, S.M. Genuth, J.M. Lachin, T.J. Orchard, P. Raskin, B. Zinman, Diabetes, Control and complication Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group.: intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353, 2643–2653 (2005)

    PubMed  Google Scholar 

  9. A. Martin, M.R. Komada, D.C. Sane, Abnormal angiogenesis in diabetes mellitus. Med. Res. Rev. 23, 117–145 (2003)

    PubMed  CAS  Google Scholar 

  10. S. Patan, Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. J. Neurooncol. 50, 1–15 (2000)

    PubMed  CAS  Google Scholar 

  11. T. Asahara, T. Murohara, A. Sullivan, M. Silver, R. van der Zee, T. Li, B. Witzenbichler, G. Schatteman, J.M. Isner, Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964–967 (1997)

    PubMed  CAS  Google Scholar 

  12. W. Risau, Mechanisms of angiogenesis. Nature 386, 671–674 (1997)

    PubMed  CAS  Google Scholar 

  13. J. Folkman, Angiogenesis. Annu. Rev. Med. 57, 1–18 (2006)

    PubMed  CAS  Google Scholar 

  14. S. Banai, M.T. Jaklitsch, M. Shou, D.F. Lazarous, M. Scheinowitz, S. Biro, S.E. Epstein, E.F. Unger, Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 89, 2183–2189 (1994)

    PubMed  CAS  Google Scholar 

  15. S. Takeshita, L.P. Zheng, E. Brogi, M. Kearney, L.Q. Pu, S. Bunting, N. Ferrara, J.F. Symes, J.M. Isner, Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J. Clin. Invest. 93, 662–670 (1994)

    PubMed  CAS  Google Scholar 

  16. E.F. Unger, S. Banai, M. Shou, D.F. Lazarous, M.T. Jaklitsch, M. Scheinowitz, R. Correa, C. Klingbeil, S.E. Epstein, Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am. J. Physiol. 266, 1588–1595 (1994)

    Google Scholar 

  17. D.F. Lazarous, M. Scheinowitz, M. Shou, E. Hodge, S. Rajanayagam, S. Hunsberger, W.G. Robison Jr, J.A. Stiber, R. Correa, S.E. Epstein, Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation 91, 145–153 (1995)

    PubMed  CAS  Google Scholar 

  18. D.F. Lazarous, M. Shou, M. Scheinowitz, E. Hodge, V. Thirumurti, A.N. Kitsiou, J.A. Stiber, A.D. Lobo, S. Hunsberger, E. Guetta, S.E. Epstein, E.F. Unger, Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. Circulation 94, 1074–1082 (1996)

    PubMed  CAS  Google Scholar 

  19. H.T. Yang, M.R. Deschenes, R.W. Ogilvie, R.L. Terjung, Basic fibroblast growth factor increases collateral blood flow in rats with femoral arterial ligation. Circ. Res. 79, 62–69 (1996)

    PubMed  CAS  Google Scholar 

  20. J.J. Lopez, R.J. Laham, A. Stamler, J.D. Pearlman, S. Bunting, A. Kaplan, J.P. Carrozza, F.W. Sellke, M. Simons, VEGF administration in chronic myocardial ischemia in pigs. Cardiovasc. Res. 40, 272–281 (1998)

    PubMed  CAS  Google Scholar 

  21. R. Morishita, S. Nakamura, S. Hayashi, Y. Taniyama, A. Moriguchi, T. Nagano, M. Taiji, H. Noguchi, S. Takeshita, K. Matsumoto, T. Nakamura, J. Higaki, T. Ogihara, Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy. Hypertension 33, 1379–1384 (1999)

    PubMed  CAS  Google Scholar 

  22. D.J. Collinson, R. Donnelly, Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur. J. Vasc. Endovasc. Surg. 28, 9–23 (2004)

    PubMed  CAS  Google Scholar 

  23. M. Heil, I. Eitenmuller, T. Schmitz-Rixen, W. Schaper, Arteriogenesis versus angiogenesis: similarities and differences. J. Cell Mol. Med. 10, 45–55 (2006)

    PubMed  CAS  Google Scholar 

  24. H. Gerhardt, M. Golding, M. Fruttiger, C. Ruhrberg, A. Lundkvist, A. Abramsson, M. Jeltsch, C. Mitchell, K. Alitalo, D. Shima, C. Betsholtz, VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163–1177 (2003)

    PubMed  CAS  Google Scholar 

  25. S. Patel-Hett, P.A. D’Amore, Signal transduction in vasculogenesis and developmental angiogenesis. Int. J. Dev. Biol. 55, 353–363 (2011)

    PubMed  CAS  Google Scholar 

  26. M. Heil, W. Schaper, Cellular mechanisms of arteriogenesis. Exs, 181–191 (2005)

  27. I. Eitenmuller, O. Volger, A. Kluge, K. Troidl, M. Barancik, W.J. Cai, M. Heil, F. Pipp, S. Fischer, A.J. Horrevoets, T. Schmitz-Rixen, W. Schaper, The range of adaptation by collateral vessels after femoral artery occlusion. Circ. Res. 99, 656–662 (2006)

    PubMed  Google Scholar 

  28. J. Waltenberger, J. Lange, A. Kranz, Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: a potential predictor for the individual capacity to develop collaterals. Circulation 102, 185–190 (2000)

    PubMed  CAS  Google Scholar 

  29. V. Tchaikovski, S. Olieslagers, F.D. Bohmer, J. Waltenberger, Diabetes mellitus activates signal transduction pathways resulting in vascular endothelial growth factor resistance of human monocytes. Circulation 120, 150–159 (2009)

    PubMed  CAS  Google Scholar 

  30. E. Tateishi-Yuyama, H. Matsubara, T. Murohara, U. Ikeda, S. Shintani, H. Masaki, K. Amano, Y. Kishimoto, K. Yoshimoto, H. Akashi, K. Shimada, T. Iwasaka, T. Imaizumi, Therapeutic angiogenesis using cell transplantation study, I.: therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 360, 427–435 (2002)

    PubMed  Google Scholar 

  31. O. Honmou, K. Houkin, T. Matsunaga, Y. Niitsu, S. Ishiai, R. Onodera, S. G. Waxman, J. D. Kocsis, Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain:134, 1790–1807 (2011)

    Google Scholar 

  32. M. Gnecchi, P. Danieli, E. Cervio, Mesenchymal stem cell therapy for heart disease. Vasc. Pharmacol. 57, 48–55 (2012)

    CAS  Google Scholar 

  33. G.O. Ouma, R.A. Jonas, M.H. Usman, E.R. Mohler 3rd, Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc. Med. 17, 174–192 (2012)

    PubMed  Google Scholar 

  34. C. Kalka, H. Masuda, T. Takahashi, W. M. Kalka-Moll, M. Silver, M. Kearney, T. Li, J. M. Isner, T. Asahara, Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc. Natl. Acad. Sci. U S A 97, 3422–3427 (2000)

    Google Scholar 

  35. O. Jeon, S.W. Kang, H.W. Lim, D. Choi, D.I. Kim, S.H. Lee, J.H. Chung, B.S. Kim, Synergistic effect of sustained delivery of basic fibroblast growth factor and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs. Biomaterials 27, 1617–1625 (2006)

    PubMed  CAS  Google Scholar 

  36. A. Aicher, M. Rentsch, K. Sasaki, J.W. Ellwart, F. Fandrich, R. Siebert, J.P. Cooke, S. Dimmeler, C. Heeschen, Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ. Res. 100, 581–589 (2007)

    PubMed  CAS  Google Scholar 

  37. M. Jiang, B. Wang, C. Wang, B. He, H. Fan, T.B. Guo, Q. Shao, L. Gao, Y. Liu, Angiogenesis by transplantation of HIF-1 alpha modified EPCs into ischemic limbs. J. Cell. Biochem. 103, 321–334 (2008)

    PubMed  CAS  Google Scholar 

  38. M. Gnecchi, Z. Zhang, A. Ni, V.J. Dzau, Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res. 103, 1204–1219 (2008)

    PubMed  CAS  Google Scholar 

  39. Y. Jeong, D.J. Mangelsdorf, Nuclear receptor regulation of stemness and stem cell differentiation. Exp. Mol. Med. 41, 525–537 (2009)

    PubMed  CAS  Google Scholar 

  40. A. Keating, Mesenchymal stromal cells: new directions. Cell stem cell 10, 709–716 (2012)

    PubMed  CAS  Google Scholar 

  41. A. Blum, W. Balkan, J.M. Hare, Advances in cell-based therapy for peripheral vascular disease. Atherosclerosis 223, 269–277 (2012)

    PubMed  CAS  Google Scholar 

  42. P. Anversa, J. Kajstura, M. Rota, A. Leri, Regenerating new heart with stem cells. J. Clin. Invest. 123, 62–70 (2013)

    PubMed  CAS  Google Scholar 

  43. S. Matoba, T. Tatsumi, T. Murohara, T. Imaizumi, Y. Katsuda, M. Ito, Y. Saito, S. Uemura, H. Suzuki, S. Fukumoto, Y. Yamamoto, R. Onodera, S. Teramukai, M. Fukushima, H. Matsubara, TACT follow-up study investigators. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (therapeutic angiogenesis by cell transplantation [tact] trial) in patients with chronic limb ischemia. Am. Heart J. 156, 1010–1018 (2008)

    PubMed  Google Scholar 

  44. J.S. Lee, J.M. Hong, G.J. Moon, P.H. Lee, Y.H. Ahn, O.Y. Bang, A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem cells 28, 1099–1106 (2010)

    PubMed  Google Scholar 

  45. G. Astori, F. Bambi, G. Soldati, D. Surder, T. Moccetti, Autologous bone marrow mononucleated cell preparation for the clinical treatment of acute myocardial infarction and peripheral arterial disease. Cytotherapy 13, 1031–1035 (2011)

    PubMed  Google Scholar 

  46. S.I. Savitz, V. Misra, M. Kasam, H. Juneja, C.S. Cox Jr, S. Alderman, I. Aisiku, S. Kar, A. Gee, J.C. Grotta, Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann. Neurol. 70, 59–69 (2011)

    PubMed  Google Scholar 

  47. D.M. Clifford, S.A. Fisher, S.J. Brunskill, C. Doree, A. Mathur, S. Watt, E. Martin-Rendon, Stem cell treatment for acute myocardial infarction (Cochrane Database Syst., Rev, 2012)

    Google Scholar 

  48. H. Zimmet, P. Porapakkham, P. Porapakkham, Y. Sata, S.J. Haas, S. Itescu, A. Forbes, H. Krum, Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. Eur. J. Heart Fail. 14, 91–105 (2012)

    PubMed  Google Scholar 

  49. C.K. Rebelatto, A.M. Aguiar, M.P. Moretao, A.C. Senegaglia, P. Hansen, F. Barchiki, J. Oliveira, J. Martins, C. Kuligovski, F. Mansur, A. Christofis, V.F. Amaral, P.S. Brofman, S. Goldenberg, L.S. Nakao, A. Correa, Dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue. Exp Biol Med (Maywood) 233, 901–913 (2008)

    CAS  Google Scholar 

  50. G.C. Schatteman, M. Dunnwald, C. Jiao, Biology of bone marrow-derived endothelial cell precursors. Am. J. Physiol. Heart Circ. Physiol. 292, H1–H18 (2007)

    PubMed  CAS  Google Scholar 

  51. D.P. Sieveking, M.K. Ng, Cell therapies for therapeutic angiogenesis: back to the bench. Vasc. med. 14, 153–166 (2009)

    PubMed  Google Scholar 

  52. G.Q. Jia, M.M. Zhang, P. Yang, J.Q. Cheng, Y.R. Lu, X.T. Wu, Effects of the different culture and isolation methods on the growth, proliferation and biology characteristics of rat bone marrow mesenchymal stem cells. Sichuan Da Xue Xue Bao Yi Xue Ban. 40, 719–723 (2009)

    PubMed  Google Scholar 

  53. N. Hibino, A. Nalbandian, L. Devine, R.S. Martinez, E. McGillicuddy, T. Yi, S. Karandish, G.A. Ortolano, T. Shin’oka, E. Snyder, C.K. Breuer, Comparison of human bone marrow mononuclear cell isolation methods for creating tissue-engineered vascular grafts: novel filter system versus traditional density centrifugation method. Tissue Eng. 17, 993–998 (2011)

    CAS  Google Scholar 

  54. M. Gnecchi, L.G. Melo, Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium. Methods Mol. Biol. 482, 281–294 (2009)

    PubMed  CAS  Google Scholar 

  55. G. Condorelli, U. Borello, L. De Angelis, M. Latronico, D. Sirabella, M. Coletta, R. Galli, G. Balconi, A. Follenzi, G. Frati, M.G. De Cusella Angelis, L. Gioglio, S. Amuchastegui, L. Adorini, L. Naldini, A. Vescovi, E. Dejana, G. Cossu, Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implications for myocardium regeneration. Proc. Natl. Acad. Sci. U. S. A. 98, 10733–10738 (2001)

    PubMed  CAS  Google Scholar 

  56. N.F. Grigoropoulos, A. Mathur, Stem cells in cardiac repair. Curr. Opin. Pharmacol. 6, 169–175 (2006)

    PubMed  CAS  Google Scholar 

  57. T.J. Burdon, A. Paul, N. Noiseux, S. Prakash, D. Shum-Tim, Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. Bone Marrow Res. 2011, 207326 (2011)

    PubMed  Google Scholar 

  58. M.C. Yoder, L.E. Mead, D. Prater, T.R. Krier, K.N. Mroueh, F. Li, R. Krasich, C.J. Temm, J.T. Prchal, D.A. Ingram, Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 109, 1801–1809 (2007)

    PubMed  CAS  Google Scholar 

  59. W. Wojakowski, U. Landmesser, R. Bachowski, T. Jadczyk, M. Tendera, Mobilization of stem and progenitor cells in cardiovascular diseases. Leukemia 26, 23–33 (2012)

    Google Scholar 

  60. M.C. Yoder, D.A. Ingram, Endothelial progenitor cell: ongoing controversy for defining these cells and their role in neoangiogenesis in the murine system. Curr. Opin. Hematol. 16, 269–273 (2009)

    PubMed  CAS  Google Scholar 

  61. M. Mayr, D. Niederseer, J. Niebauer, From bench to bedside: what physicians need to know about endothelial progenitor cells. Am. J. Med. 124, 489–497 (2011)

    PubMed  Google Scholar 

  62. S. Shintani, T. Murohara, H. Ikeda, T. Ueno, T. Honma, A. Katoh, K. Sasaki, T. Shimada, Y. Oike, T. Imaizumi, Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103, 2776–2779 (2001)

    PubMed  CAS  Google Scholar 

  63. P. Huang, S. Li, M. Han, Z. Xiao, R. Yang, Z.C. Han, Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 28, 2155–2160 (2005)

    PubMed  Google Scholar 

  64. H. Ince, M. Petzsch, H.D. Kleine, H. Eckard, T. Rehders, D. Burska, S. Kische, M. Freund, C.A. Nienaber, Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and stem cell liberation in evolving acute myocardial infarction by granulocyte colony-stimulating factor (FIRSTLINE-AMI) trial. Circulation 112, I73–I80 (2005)

    PubMed  Google Scholar 

  65. R.S. Ripa, E. Jorgensen, Y. Wang, J.J. Thune, J.C. Nilsson, L. Sondergaard, H.E. Johnsen, L. Kober, P. Grande, J. Kastrup, Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation 113, 1983–1992 (2006)

    PubMed  CAS  Google Scholar 

  66. Y. Suarez, B.R. Shepherd, D.A. Rao, J.S. Pober, Alloimmunity to human endothelial cells derived from cord blood progenitors. J. Immunol. 179, 7488–7496 (2007)

    PubMed  CAS  Google Scholar 

  67. E. M. Horwitz, P. L. Gordon, W. K. Koo, J. C. Marx, M. D. Neel, R. Y. McNall, L. Muul, T. Hofmann, Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc. Natl. Acad. Sci. U S A 99, 8932–8937 (2002)

    Google Scholar 

  68. H.M. Lazarus, S.E. Haynesworth, S.L. Gerson, N.S. Rosenthal, A.I. Caplan, Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 16, 557–564 (1995)

    PubMed  CAS  Google Scholar 

  69. J. Cai, M.L. Weiss, M.S. Rao, In search of “stemness”. Exp. Hematol. 32, 585–598 (2004)

    PubMed  Google Scholar 

  70. N.J. Zvaifler, L. Marinova-Mutafchieva, G. Adams, C.J. Edwards, J. Moss, J.A. Burger, R.N. Maini, Mesenchymal precursor cells in the blood of normal individuals. Arthr. res. 2, 477–488 (2000)

    CAS  Google Scholar 

  71. J.G. Toma, M. Akhavan, K.J. Fernandes, F. Barnabe-Heider, A. Sadikot, D.R. Kaplan, F.D. Miller, Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 3, 778–784 (2001)

    PubMed  CAS  Google Scholar 

  72. U. Noth, A.M. Osyczka, R. Tuli, N.J. Hickok, K.G. Danielson, R.S. Tuan, Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J. Orthop. Res. 20, 1060–1069 (2002)

    PubMed  Google Scholar 

  73. I. Rogers, R.F. Casper, Umbilical cord blood stem cells. Best. Pract. Res. Clin. Obstet. Gynaecol. 18, 893–908 (2004)

    PubMed  Google Scholar 

  74. S. Kern, H. Eichler, J. Stoeve, H. Kluter, K. Bieback, Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem cells 24, 1294–1301 (2006)

    PubMed  CAS  Google Scholar 

  75. A.H. Klopp, A. Gupta, E. Spaeth, M. Andreeff, F. Marini 3rd, Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem cells 29, 11–19 (2011)

    PubMed  CAS  Google Scholar 

  76. Y. Jiang, B.N. Jahagirdar, R.L. Reinhardt, R.E. Schwartz, C.D. Keene, X.R. Ortiz-Gonzalez, M. Reyes, T. Lenvik, T. Lund, M. Blackstad, J. Du, S. Aldrich, A. Lisberg, W.C. Low, D.A. Largaespada, C.M. Verfaillie, Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41–49 (2002)

    PubMed  CAS  Google Scholar 

  77. M. Dominici, K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D. Prockop, E. Horwitz, Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315–317 (2006)

    PubMed  CAS  Google Scholar 

  78. H. Nakagami, R. Morishita, K. Maeda, Y. Kikuchi, T. Ogihara, Y. Kaneda, Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J. Atheroscler. Thromb. 13, 77–81 (2006)

    PubMed  Google Scholar 

  79. G. Chamberlain, J. Fox, B. Ashton, J. Middleton, Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem cells 25, 2739–2749 (2007)

    PubMed  CAS  Google Scholar 

  80. S. Tomita, R. K. Li, R. D. Weisel, D. A. Mickle, E. J. Kim, T. Sakai, Z. Q. Jia, Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100, II247–256 (1999)

    Google Scholar 

  81. M.F. Pittenger, B.J. Martin, Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 95, 9–20 (2004)

    PubMed  CAS  Google Scholar 

  82. D.G. Phinney, D.J. Prockop, Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem cells 25, 2896–2902 (2007)

    PubMed  Google Scholar 

  83. B.A. Bunnell, M. Flaat, C. Gagliardi, B. Patel, C. Ripoll, Adipose-derived stem cells: isolation, expansion and differentiation. Methods 45, 115–120 (2008)

    PubMed  CAS  Google Scholar 

  84. T. Murohara, Autologous adipose tissue as a new source of progenitor cells for therapeutic angiogenesis. J. Cardiol. 53, 155–163 (2009)

    PubMed  Google Scholar 

  85. K. Kondo, S. Shintani, R. Shibata, H. Murakami, R. Murakami, M. Imaizumi, Y. Kitagawa, T. Murohara, Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. Arterioscler. Thromb. Vasc. Biol. 29, 61–66 (2009)

    PubMed  CAS  Google Scholar 

  86. J. Rehman, D. Traktuev, J. Li, S. Merfeld-Clauss, C.J. Temm-Grove, J.E. Bovenkerk, C.L. Pell, B.H. Johnstone, R.V. Considine, K.L. March, Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109, 1292–1298 (2004)

    PubMed  Google Scholar 

  87. H. Nakagami, K. Maeda, R. Morishita, S. Iguchi, T. Nishikawa, Y. Takami, Y. Kikuchi, Y. Saito, K. Tamai, T. Ogihara, Y. Kaneda, Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells. Arterioscler. Thromb. Vasc. Biol. 25, 2542–2547 (2005)

    PubMed  CAS  Google Scholar 

  88. F. Mosna, L. Sensebe, M. Krampera, Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem cells dev. 19, 1449–1470 (2010)

    PubMed  CAS  Google Scholar 

  89. P.C. Baer, H. Geiger, Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem cells int. 2012, 812693 (2012)

    PubMed  Google Scholar 

  90. N. Tremain, J. Korkko, D. Ibberson, G.C. Kopen, C. DiGirolamo, D.G. Phinney, MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages. Stem cells 19, 408–418 (2001)

    PubMed  CAS  Google Scholar 

  91. W. Wagner, F. Wein, A. Seckinger, M. Frankhauser, U. Wirkner, U. Krause, J. Blake, C. Schwager, V. Eckstein, W. Ansorge, A.D. Ho, Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp. Hem. 33, 1402–1416 (2005)

    CAS  Google Scholar 

  92. W. Wagner, R.E. Feldmann Jr, A. Seckinger, M.H. Maurer, F. Wein, J. Blake, U. Krause, A. Kalenka, H.F. Burgers, R. Saffrich, P. Wuchter, W. Kuschinsky, A.D. Ho, The heterogeneity of human mesenchymal stem cell preparations–evidence from simultaneous analysis of proteomes and transcriptomes. Exp. Hem. 34, 536–548 (2006)

    CAS  Google Scholar 

  93. P. Dentelli, C. Barale, G. Togliatto, A. Trombetta, C. Olgasi, M. Gili, C. Riganti, M. Toppino, M.F. Brizzi, A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells. Diabetologia 56, 173–184 (2013)

    PubMed  CAS  Google Scholar 

  94. J.A. Thomson, J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall, J.M. Jones, Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998)

    PubMed  CAS  Google Scholar 

  95. H.J. Rippon, A.E. Bishop, Embryonic stem cells. Cell Prolif. 37, 23–34 (2004)

    PubMed  CAS  Google Scholar 

  96. B. Blum, N. Benvenisty, The tumorigenicity of human embryonic stem cells. Adv. Cancer Res. 100, 133–158 (2008)

    PubMed  Google Scholar 

  97. K. Takahashi, S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006)

    PubMed  CAS  Google Scholar 

  98. N.J. Leeper, A.L. Hunter, J.P. Cooke, Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells. Circulation 122, 517–526 (2010)

    PubMed  Google Scholar 

  99. K.S. Volz, E. Miljan, A. Khoo, J.P. Cooke, Development of pluripotent stem cells for vascular therapy. Vasc. Pharmacol. 56, 288–296 (2012)

    CAS  Google Scholar 

  100. K. Okita, M. Nakagawa, H. Hyenjong, T. Ichisaka, S. Yamanaka, Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949–953 (2008)

    PubMed  CAS  Google Scholar 

  101. M. Bellin, M.C. Marchetto, F.H. Gage, C.L. Mummery, Induced pluripotent stem cells: the new patient? Nat. Rev. Mol. Cell Biol. 13, 713–726 (2012)

    PubMed  Google Scholar 

  102. J.M. Hill, G. Zalos, J.P. Halcox, W.H. Schenke, M.A. Waclawiw, A.A. Quyyumi, T. Finkel, Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Eng. J. Med. 348, 593–600 (2003)

    Google Scholar 

  103. G.P. Fadini, C. Agostini, A. Avogaro, Endothelial progenitor cells and vascular biology in diabetes mellitus: current knowledge and future perspectives. Curr. Diabetes Rev. 1, 41–58 (2005)

    PubMed  CAS  Google Scholar 

  104. G. Togliatto, A. Trombetta, P. Dentelli, A. Baragli, A. Rosso, R. Granata, D. Ghigo, L. Pegoraro, E. Ghigo, M.F. Brizzi, Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes. Diabetes 59, 1016–1025 (2010)

    PubMed  CAS  Google Scholar 

  105. M.S. Ruiter, J.M. van Golde, N.C. Schaper, C.D. Stehouwer, M.S. Huijberts, Diabetes impairs arteriogenesis in the peripheral circulation: review of molecular mechanisms. Clin. Sci. (Lond.) 119, 225–238 (2010)

    CAS  Google Scholar 

  106. O.M. Tepper, R.D. Galiano, J.M. Capla, C. Kalka, P.J. Gagne, G.R. Jacobowitz, J.P. Levine, G.C. Gurtner, Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106, 2781–2786 (2002)

    PubMed  Google Scholar 

  107. C.J. Loomans, E.J. de Koning, F.J. Staal, M.B. Rookmaaker, C. Verseyden, H.C. de Boer, M.C. Verhaar, B. Braam, T.J. Rabelink, A.J. van Zonneveld, Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 53, 195–199 (2004)

    PubMed  CAS  Google Scholar 

  108. A. Trombetta, G. Togliatto, A. Rosso, P. Dentelli, C. Olgasi, P. Cotogni, M. F. Brizzi, Increase of palmitic acid concentration impairs endothelial progenitor cell and bone marrow-derived progenitor cell bioavailability: role of the signal transducer and activator of transcription 5/peroxisome proliferator-activated receptor gamma transcriptional complex. diabetes (2012)

  109. A. Rosso, A. Balsamo, R. Gambino, P. Dentelli, R. Falcioni, M. Cassader, L. Pegoraro, G. Pagano, M.F. Brizzi, p53 Mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes. J. Biol. Chem. 281, 4339–4347 (2006)

    PubMed  CAS  Google Scholar 

  110. J.W. Baynes, Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405–412 (1991)

    PubMed  CAS  Google Scholar 

  111. G.C. Schatteman, H.D. Hanlon, C. Jiao, S.G. Dodds, B.A. Christy, Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J. Clin. Invest. 106, 571–578 (2000)

    PubMed  CAS  Google Scholar 

  112. M. Albiero, A. Avogaro, G. P. Fadini, Restoring stem cell mobilization to promote vascular repair in diabetes. Vasc. pharmacol. (2013)

  113. G. P. Fadini, A. Avogaro, Diabetes impairs mobilization of stem cells for the treatment of cardiovascular disease: A meta-regression analysis. Int. J. Cardiol. (2012)

  114. J. Yan, G. Tie, S. Wang, K. E. Messina, S. DiDato, S. Guo, L. M. Messina, Type 2 diabetes restricts multipotency of mesenchymal stem cells and impairs their capacity to augment postischemic neovascularization in db/db mice. J. Am. Heart Assoc. 1(6), e002238 (2012)

  115. C. Berry, J.C. Tardif, M.G. Bourassa, Coronary heart disease in patients with diabetes: part I: recent advances in prevention and noninvasive management. J. Am. Coll. Cardiol. 49, 631–642 (2007)

    PubMed  CAS  Google Scholar 

  116. R.M. Jacoby, R.W. Nesto, Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. J. Am. Coll. Cardiol. 20, 736–744 (1992)

    PubMed  CAS  Google Scholar 

  117. S.L. Woodfield, C.F. Lundergan, J.S. Reiner, S.W. Greenhouse, M.A. Thompson, S.C. Rohrbeck, Y. Deychak, M.L. Simoons, R.M. Califf, E.J. Topol, A.M. Ross, Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J. Am. Coll. Cardiol. 28, 1661–1669 (1996)

    PubMed  CAS  Google Scholar 

  118. S. Yusuf, G. Dagenais, J. Pogue, J. Bosch, P. Sleight, Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N. Eng. J. Med. 342, 154–160 (2000)

    CAS  Google Scholar 

  119. M. Luo, X. Guan, E.D. Luczak, D. Lang, W. Kutschke, Z. Gao, J. Yang, P. Glynn, S. Sossalla, P.D. Swaminathan, R.M. Weiss, B. Yang, A.G. Rokita, L.S. Maier, I.R. Efimov, T.J. Hund, M.E. Anderson, Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J. Clin. Invest. 123, 1262–1274 (2013)

    PubMed  CAS  Google Scholar 

  120. P. Valensi, E. Cosson, It is not yet the time to stop screening diabetic patients for silent myocardial ischaemia. Diabetes Metab. 36, 91–96 (2010)

    PubMed  CAS  Google Scholar 

  121. C. Gazzaruso, A. Coppola, T. Montalcini, C. Valenti, A. Garzaniti, G. Pelissero, F. Salvucci, P. Gallotti, A. Pujia, C. Falcone, S.B. Solerte, A. Giustina, Erectile dysfunction can improve the effectiveness of the current guidelines for the screening for asymptomatic coronary artery disease in diabetes. Endocrine 40, 273–279 (2011)

    PubMed  CAS  Google Scholar 

  122. A. Prasad, G.W. Stone, T.D. Stuckey, C.O. Costantini, P.J. Zimetbaum, M. McLaughlin, R. Mehran, E. Garcia, J.E. Tcheng, D.A. Cox, C.L. Grines, A.J. Lansky, B.J. Gersh, Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction. J. Am. Coll. Cardiol. 45, 508–514 (2005)

    PubMed  Google Scholar 

  123. K.H. Mak, E.J. Topol, Emerging concepts in the management of acute myocardial infarction in patients with diabetes mellitus. J. Am. Coll. Cardiol. 35, 563–568 (2000)

    PubMed  CAS  Google Scholar 

  124. X. Yin, Y. Zheng, X. Zhai, X. Zhao, L. Cai, Diabetic inhibition of preconditioning- and postconditioning-mediated myocardial protection against ischemia/reperfusion injury. Exp. Diabetes Res. 2012, 198048 (2012)

    PubMed  Google Scholar 

  125. B.E. Strauer, R. Kornowski, Stem cell therapy in perspective. Circulation 107, 929–934 (2003)

    PubMed  Google Scholar 

  126. M. T. Abdel Aziz, M. F. El-Asmar, M. Haidara, H. M. Atta, N. K. Roshdy, L. A. Rashed, D. Sabry, M. A. Youssef, A. T. Abdel Aziz, M. Moustafa, Effect of bone marrow-derived mesenchymal stem cells on cardiovascular complications in diabetic rats. Med Sci Monit. 14, BR249–255 (2008)

  127. J.H. Li, N. Zhang, J.A. Wang, Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. J. Endocrinol. Invest. 31, 103–110 (2008)

    PubMed  CAS  Google Scholar 

  128. J. A. Govaert, R. J. Swijnenburg, S. Schrepfer, X. Xie, K. E. van der Bogt, G. Hoyt, W. Stein, K. J. Ransohoff, R. C. Robbins, J. C. Wu, Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium. J Heart Lung Transplant. 28, 1158–1165 e1151 (2009)

    Google Scholar 

  129. T. Kinnaird, E. Stabile, M.S. Burnett, C.W. Lee, S. Barr, S. Fuchs, S.E. Epstein, Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ. Res. 94, 678–685 (2004)

    PubMed  CAS  Google Scholar 

  130. M. Gnecchi, H. He, O.D. Liang, L.G. Melo, F. Morello, H. Mu, N. Noiseux, L. Zhang, R.E. Pratt, J.S. Ingwall, V.J. Dzau, Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med. 11, 367–368 (2005)

    PubMed  CAS  Google Scholar 

  131. M. Gnecchi, H. He, N. Noiseux, O.D. Liang, L. Zhang, F. Morello, H. Mu, L.G. Melo, R.E. Pratt, J.S. Ingwall, V.J. Dzau, Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20, 661–669 (2006)

    PubMed  CAS  Google Scholar 

  132. R. Mingliang, Z. Bo, W. Zhengguo, Stem cells for cardiac repair: status, mechanisms, and new strategies. Stem cells int. 2011, 310928 (2011)

    PubMed  Google Scholar 

  133. Y. Bai, T. Sun, P. Ye, Age, gender and diabetic status are associated with effects of bone marrow cell therapy on recovery of left ventricular function after acute myocardial infarction: a systematic review and meta-analysis. Ageing Res. Rev. 9, 418–423 (2010)

    PubMed  Google Scholar 

  134. F.M. Rauscher, P.J. Goldschmidt-Clermont, B.H. Davis, T. Wang, D. Gregg, P. Ramaswami, A.M. Pippen, B.H. Annex, C. Dong, D.A. Taylor, Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108, 457–463 (2003)

    PubMed  Google Scholar 

  135. L. Menegazzo, M. Albiero, A. Avogaro, G.P. Fadini, Endothelial progenitor cells in diabetes mellitus. BioFactors 38, 194–202 (2012)

    PubMed  CAS  Google Scholar 

  136. W. Ruan, C.Z. Pan, G.Q. Huang, Y.L. Li, J.B. Ge, X.H. Shu, Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging. Chin. Med. J. (Engl) 118, 1175–1181 (2005)

    Google Scholar 

  137. R.S. Karpov, S.V. Popov, V.A. Markov, T.E. Suslova, V.V. Ryabov, Y.S. Poponina, A.L. Krylov, S.V. Sazonova, Autologous mononuclear bone marrow cells during reparative regeneratrion after acute myocardial infarction. Bull. Exp. Biol. Med. 140, 640–643 (2005)

    PubMed  CAS  Google Scholar 

  138. S. Janssens, C. Dubois, J. Bogaert, K. Theunissen, C. Deroose, W. Desmet, M. Kalantzi, L. Herbots, P. Sinnaeve, J. Dens, J. Maertens, F. Rademakers, S. Dymarkowski, O. Gheysens, J. Van Cleemput, G. Bormans, J. Nuyts, A. Belmans, L. Mortelmans, M. Boogaerts, F. Van de Werf, Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367, 113–121 (2006)

    PubMed  Google Scholar 

  139. R.C. Huang, K. Yao, Y.Z. Zou, L. Ge, J.Y. Qian, J. Yang, S. Yang, Y.H. Niu, Y.L. Li, Y.Q. Zhang, F. Zhang, S.K. Xu, S.H. Zhang, A.J. Sun, J.B. Ge, Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction. Zhonghua yi xue za zhi 86, 1107–1110 (2006)

    PubMed  Google Scholar 

  140. H.J. Kang, H.Y. Lee, S.H. Na, S.A. Chang, K.W. Park, H.K. Kim, S.Y. Kim, H.J. Chang, W. Lee, W.J. Kang, B.K. Koo, Y.J. Kim, D.S. Lee, D.W. Sohn, K.S. Han, B.H. Oh, Y.B. Park, H.S. Kim, Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation 114, I145–I151 (2006)

    PubMed  Google Scholar 

  141. J. Ge, Y. Li, J. Qian, J. Shi, Q. Wang, Y. Niu, B. Fan, X. Liu, S. Zhang, A. Sun, Y. Zou, Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart 92, 1764–1767 (2006)

    PubMed  CAS  Google Scholar 

  142. F. Cao, D. Sun, C. Li, K. Narsinh, L. Zhao, X. Li, X. Feng, J. Zhang, Y. Duan, J. Wang, D. Liu, H. Wang, Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up. Eur. Heart J. 30, 1986–1994 (2009)

    PubMed  Google Scholar 

  143. S. Grajek, M. Popiel, L. Gil, P. Breborowicz, M. Lesiak, R. Czepczynski, K. Sawinski, E. Straburzynska-Migaj, A. Araszkiewicz, A. Czyz, M. Kozlowska-Skrzypczak, M. Komarnicki, Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur.Heart J. l31, 691–702 (2010)

  144. J. Chen, J. Chen, S. Chen, C. Zhang, L. Zhang, X. Xiao, A. Das, Y. Zhao, B. Yuan, M. Morris, B. Zhao, Y. Chen, Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice. PLoS ONE 7, e50105 (2012)

    PubMed  CAS  Google Scholar 

  145. J.M. Hare, J.H. Traverse, T.D. Henry, N. Dib, R.K. Strumpf, S.P. Schulman, G. Gerstenblith, A.N. DeMaria, A.E. Denktas, R.S. Gammon, J.B. Hermiller Jr, M.A. Reisman, G.L. Schaer, W. Sherman, A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J. Am. Coll. Cardiol. 54, 2277–2286 (2009)

    PubMed  CAS  Google Scholar 

  146. M. Shanmugasundaram, V.K. Ram, U.C. Luft, M. Szerlip, J.S. Alpert, Peripheral arterial disease–what do we need to know? Clin. Cardiol. 34, 478–482 (2011)

    PubMed  Google Scholar 

  147. American Diabetes Association, Peripheral arterial disease in people with diabetes. Diabetes Care 26, 3333–3341 (2003)

    Google Scholar 

  148. E.B. Jude, I. Eleftheriadou, N. Tentolouris, Peripheral arterial disease in diabetes–a review. Diabet. Med. 27, 4–14 (2010)

    PubMed  CAS  Google Scholar 

  149. S. Gandhi, I. Weinberg, R. Margey, M.R. Jaff, Comprehensive medical management of peripheral arterial disease. Prog. Cardiovasc. Dis. 54, 2–13 (2011)

    PubMed  Google Scholar 

  150. R. Baffour, J. Berman, J.L. Garb, S.W. Rhee, J. Kaufman, P. Friedmann, Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor. J. Vasc. Surg. 16, 181–191 (1992)

    PubMed  CAS  Google Scholar 

  151. P. Carmeliet, L. Moons, A. Luttun, V. Vincenti, V. Compernolle, M. De Mol, Y. Wu, F. Bono, L. Devy, H. Beck, D. Scholz, T. Acker, T. DiPalma, M. Dewerchin, A. Noel, I. Stalmans, A. Barra, S. Blacher, T. VandenDriessche, A. Ponten, U. Eriksson, K.H. Plate, J.M. Foidart, W. Schaper, D.S. Charnock-Jones, D.J. Hicklin, J.M. Herbert, D. Collen, M.G. Persico, Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat. Med. 7, 575–583 (2001)

    PubMed  CAS  Google Scholar 

  152. C. Borselli, H. Storrie, F. Benesch-Lee, D. Shvartsman, C. Cezar, J.W. Lichtman, H.H. Vandenburgh, D.J. Mooney, Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc. Natl. Acad. Sci. U S A107, 3287–3292 (2010)

    Google Scholar 

  153. S. Yla-Herttuala, K. Alitalo, Gene transfer as a tool to induce therapeutic vascular growth. Nat. Med. 9, 694–701 (2003)

    PubMed  Google Scholar 

  154. C.A. Mack, C.J. Magovern, K.T. Budenbender, S.R. Patel, E.A. Schwarz, P. Zanzonico, B. Ferris, T. Sanborn, P. Isom, B. Ferris, T. Sanborn, O.W. Isom, R.G. Crystal, T.K. Rosengart, Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. J. Vasc. Surg. 27, 699–709 (1998)

    PubMed  CAS  Google Scholar 

  155. N. Ohara, H. Koyama, T. Miyata, H. Hamada, S.I. Miyatake, M. Akimoto, H. Shigematsu, Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia. Gene Ther. 8, 837–845 (2001)

    PubMed  CAS  Google Scholar 

  156. D.S. Chang, H. Su, G.L. Tang, L.S. Brevetti, R. Sarkar, R. Wang, Y.W. Kan, L.M. Messina, Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb. Mol. Ther. 7, 44–51 (2003)

    PubMed  CAS  Google Scholar 

  157. F.D. Olea, G. Vera Janavel, L. Cuniberti, G. Yannarelli, P. Cabeza Meckert, J. Cors, L. Valdivieso, G. Lev, O. Mendiz, A. Bercovich, M. Criscuolo, C. Melo, R. Laguens, A. Crottogini, Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia. Gene Ther. 16, 716–723 (2009)

    PubMed  CAS  Google Scholar 

  158. E.V. De Paula, M.C. Flores-Nascimento, V.R. Arruda, R.A. Garcia, C.D. Ramos, A.T. Guillaumon, J.M. Annichino-Bizzacchi, Dual gene transfer of fibroblast growth factor-2 and platelet derived growth factor-BB using plasmid deoxyribonucleic acid promotes effective angiogenesis and arteriogenesis in a rodent model of hindlimb ischemia. Transl. Res.: J. Lab. Clin. Med. 153, 232–239 (2009)

    Google Scholar 

  159. E.B. Sneider, P.T. Nowicki, L.M. Messina, Regenerative medicine in the treatment of peripheral arterial disease. J. Cell. Biochem. 108, 753–761 (2009)

    PubMed  CAS  Google Scholar 

  160. S. Rajagopalan, E.R. Mohler 3rd, R.J. Lederman, F.O. Mendelsohn, J.F. Saucedo, C.K. Goldman, J. Blebea, J. Macko, P.D. Kessler, H.S. Rasmussen, B.H. Annex, Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 108, 1933–1938 (2003)

    PubMed  CAS  Google Scholar 

  161. R.J. Powell, M. Simons, F.O. Mendelsohn, G. Daniel, T.D. Henry, M. Koga, R. Morishita, B.H. Annex, Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation 118, 58–65 (2008)

    PubMed  CAS  Google Scholar 

  162. S. Nikol, I. Baumgartner, E. Van Belle, C. Diehm, A. Visona, M.C. Capogrossi, N. Ferreira-Maldent, A. Gallino, M.G. Wyatt, L.D. Wijesinghe, M. Fusari, D. Stephan, J. Emmerich, G. Pompilio, F. Vermassen, E. Pham, V. Grek, M. Coleman, F. Meyer, T. Investigators, Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol. Ther. 16, 972–978 (2008)

    PubMed  CAS  Google Scholar 

  163. G. Cobellis, A. Silvestroni, S. Lillo, G. Sica, C. Botti, C. Maione, V. Schiavone, S. Rocco, G. Brando, V. Sica, Long-term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease. Bone Marrow Transplant. 42, 667–672 (2008)

    PubMed  CAS  Google Scholar 

  164. A. Ranghino, V. Cantaluppi, C. Grange, L. Vitillo, F. Fop, L. Biancone, M.C. Deregibus, C. Tetta, G.P. Segoloni, G. Camussi, Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia. Int. J. Immunopathol. Pharmacol. 25, 75–85 (2012)

    PubMed  CAS  Google Scholar 

  165. R.B. Van Tongeren, J.F. Hamming, W.E. Fibbe, V. Van Weel, S.J. Frerichs, A.M. Stiggelbout, J.H. Van Bockel, J.H. Lindeman, Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J. Cardiovasc. Surg. (Torino) 49, 51–58 (2008)

    Google Scholar 

  166. K. Lenk, V. Adams, P. Lurz, S. Erbs, A. Linke, S. Gielen, A. Schmidt, D. Scheinert, G. Biamino, F. Emmrich, G. Schuler, R. Hambrecht, Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur. Heart J. 26, 1903–1909 (2005)

    PubMed  Google Scholar 

  167. R.W. Sprengers, F.L. Moll, M. Teraa, M.C. Verhaar, J.S. Group, Rationale and design of the JUVENTAS trial for repeated intra-arterial infusion of autologous bone marrow-derived mononuclear cells in patients with critical limb ischemia. J. Vasc. Surg. 51, 1564–1568 (2010)

    PubMed  Google Scholar 

  168. W. Fan, D. Sun, J. Liu, D. Liang, Y. Wang, K.H. Narsinh, Y. Li, X. Qin, J. Liang, J. Tian, F. Cao, Adipose stromal cells amplify angiogenic signaling via the VEGF/mTOR/Akt pathway in a murine hindlimb ischemia model: a 3D multimodality imaging study. PLoS ONE 7, e45621 (2012)

    PubMed  CAS  Google Scholar 

  169. L.R. Wechsler, Intravenous thrombolytic therapy for acute ischemic stroke. N. Eng. J. Med. 364, 2138–2146 (2011)

    CAS  Google Scholar 

  170. L.H. Schwamm, M.J. Reeves, W. Pan, E.E. Smith, M.R. Frankel, D. Olson, X. Zhao, E. Peterson, G.C. Fonarow, Race/ethnicity, quality of care, and outcomes in ischemic stroke. Circulation 121, 1492–1501 (2010)

    PubMed  Google Scholar 

  171. L.B. Goldstein, C.D. Bushnell, R.J. Adams, L.J. Appel, L.T. Braun, S. Chaturvedi, M.A. Creager, A. Culebras, R.H. Eckel, R.G. Hart, J.A. Hinchey, V.J. Howard, E.C. Jauch, S.R. Levine, J.F. Meschia, W.S. Moore, J.V. Nixon, T.A. Pearson, American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Epidemiology and Prevention; Council for High Blood Pressure Research,; Council on Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research.: guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 517–584 (2011)

    PubMed  Google Scholar 

  172. J.P. Broderick, P.M. Meyers, Acute stroke therapy at the crossroads. JAMA 306, 2026–2028 (2011)

    PubMed  CAS  Google Scholar 

  173. H.P. Adams Jr, G. del Zoppo, M.J. Alberts, D.L. Bhatt, L. Brass, A. Furlan, R.L. Grubb, R.T. Higashida, E.C. Jauch, C. Kidwell, P.D. Lyden, L.B. Morgenstern, A.I. Qureshi, R.H. Rosenwasser, P.A. Scott, E.F. Wijdicks, American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 38, 1655–1711 (2007)

    PubMed  Google Scholar 

  174. N.K. Mishra, S.M. Davis, M. Kaste, K.R. Lees, V. Collaboration, Comparison of outcomes following thrombolytic therapy among patients with prior stroke and diabetes in the Virtual International Stroke Trials Archive (VISTA). Diabetes Care 33, 2531–2537 (2010)

    PubMed  Google Scholar 

  175. D.J. Maron, W.E. Boden, J.A. Spertus, P.M. Hartigan, G.B. Mancini, S.P. Sedlis, W.J. Kostuk, B.R. Chaitman, L.J. Shaw, D.S. Berman, M. Dada, K.K. Teo, W.S. Weintraub, R.A. O’Rourke, COURAGE Trial Research Group: impact of metabolic syndrome and diabetes on prognosis and outcomes with early percutaneous coronary intervention in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial. J. Am. Coll. Cardiol. 58, 131–137 (2011)

    PubMed  Google Scholar 

  176. C. Rosso, J.C. Corvol, C. Pires, S. Crozier, Y. Attal, S. Jacqueminet, S. Deltour, G. Multlu, A. Leger, I. Meresse, C. Payan, D. Dormont, Y. Samson, Intensive versus subcutaneous insulin in patients with hyperacute stroke: results from the randomized INSULINFARCT trial. Stroke 43, 2343–2349 (2012)

    PubMed  Google Scholar 

  177. O.Y. Bang, J.S. Lee, P.H. Lee, G. Lee, Autologous mesenchymal stem cell transplantation in stroke patients. Ann. Neurol. 57, 874–882 (2005)

    PubMed  Google Scholar 

  178. M. A. Friedrich, M. P. Martins, M. D. Araujo, C. Klamt, L. Vedolin, B. Garicochea, E. F. Raupp, J. S. Ammar, D. C. Machado, J. C. Costa, R. G. Nogueira, P. H. Rosado-de-Castro, R. Mendez-Otero, G. R. de Freitas, Intra-arterial infusion of autologous bone-marrow mononuclear cells in patients with moderate to severe middle-cerebral-artery acute ischemic stroke. Cell Transplant. (2011)

  179. M. Chopp, Y. Li, Treatment of neural injury with marrow stromal cells. Lancet neurol. 1, 92–100 (2002)

    PubMed  Google Scholar 

  180. A. Taguchi, T. Matsuyama, H. Moriwaki, T. Hayashi, K. Hayashida, K. Nagatsuka, K. Todo, K. Mori, D.M. Stern, T. Soma, H. Naritomi, Circulating CD34-positive cells provide an index of cerebrovascular function. Circulation 109, 2972–2975 (2004)

    PubMed  Google Scholar 

  181. T. Sobrino, O. Hurtado, M.A. Moro, M. Rodriguez-Yanez, M. Castellanos, D. Brea, O. Moldes, M. Blanco, J.F. Arenillas, R. Leira, A. Davalos, I. Lizasoain, J. Castillo, The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke 38, 2759–2764 (2007)

    PubMed  Google Scholar 

  182. H.K. Yip, L.T. Chang, W.N. Chang, C.H. Lu, C.W. Liou, M.Y. Lan, J.S. Liu, A.A. Youssef, H.W. Chang, Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke 39, 69–74 (2008)

    PubMed  Google Scholar 

  183. F. Pescini, F. Cesari, B. Giusti, C. Sarti, E. Zicari, S. Bianchi, M.T. Dotti, A. Federico, M. Balestrino, A. Enrico, C. Gandolfo, A.M. Gori, R. Abbate, L. Pantoni, D. Inzitari, Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 41, 218–223 (2010)

    PubMed  Google Scholar 

  184. J. Chen, X. Ye, T. Yan, C. Zhang, X.P. Yang, X. Cui, Y. Cui, A. Zacharek, C. Roberts, X. Liu, X. Dai, M. Lu, M. Chopp, Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats. Stroke 42, 3551–3558 (2011)

    PubMed  Google Scholar 

  185. G.P. Fadini, M. Miorin, M. Facco, S. Bonamico, I. Baesso, F. Grego, M. Menegolo, S.V. de Kreutzenberg, A. Tiengo, C. Agostini, A. Avogaro, Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J. Am. Coll. Cardiol. 45, 1449–1457 (2005)

    PubMed  CAS  Google Scholar 

  186. S.A. Sorrentino, F.H. Bahlmann, C. Besler, M. Muller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horvath, A. Limbourg, F. Limbourg, D. Fliser, H. Haller, H. Drexler, U. Landmesser, Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 116, 163–173 (2007)

    PubMed  CAS  Google Scholar 

  187. P. Dentelli, A. Trombetta, G. Togliatto, A. Zeoli, A. Rosso, B. Uberti, F. Orso, D. Taverna, L. Pegoraro, M.F. Brizzi, Formation of STAT5/PPARgamma transcriptional complex modulates angiogenic cell bioavailability in diabetes. Arterioscler. Thromb. Vasc. Biol. 29, 114–120 (2009)

    PubMed  CAS  Google Scholar 

  188. G. Togliatto, A. Trombetta, P. Dentelli, A. Rosso, M.F. Brizzi, MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage. Diabetologia 54, 1930–1940 (2011)

    PubMed  CAS  Google Scholar 

  189. K. Sasaki, C. Heeschen, A. Aicher, T. Ziebart, J. Honold, C. Urbich, L. Rossig, U. Koehl, M. Koyanagi, A. Mohamed, R. P. Brandes, H. Martin, A. M. Zeiher, S. Dimmeler, Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy. Proc. Natl. Acad. Sci. U S A. 103, 14537–14541 (2006)

    Google Scholar 

  190. D.H. Walter, U. Rochwalsky, J. Reinhold, F. Seeger, A. Aicher, C. Urbich, I. Spyridopoulos, J. Chun, V. Brinkmann, P. Keul, B. Levkau, A.M. Zeiher, S. Dimmeler, J. Haendeler, Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arterioscler. Thromb. Vasc. Biol. 27, 275–282 (2007)

    PubMed  CAS  Google Scholar 

  191. S. Murasawa, J. Llevadot, M. Silver, J.M. Isner, D.W. Losordo, T. Asahara, Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation 106, 1133–1139 (2002)

    PubMed  CAS  Google Scholar 

  192. M.I. Niagara, H. Haider, S. Jiang, M. Ashraf, Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative stress and promote angiomyogenesis via release of paracrine factors in the infarcted heart. Circ. Res. 100, 545–555 (2007)

    PubMed  CAS  Google Scholar 

  193. F.H. Seeger, A.M. Zeiher, S. Dimmeler, Cell-enhancement strategies for the treatment of ischemic heart disease. Nat. Clin. Pract. Cardiovasc. Med. 4, S110–S113 (2007)

    PubMed  CAS  Google Scholar 

  194. K. Larsen, C. Cheng, D. Tempel, S. Parker, S. Yazdani, W.K. den Dekker, J.H. Houtgraaf, R. de Jong, S. Swager-ten Hoor, E. Ligtenberg, S.R. Hanson, S. Rowland, S. Rowland, S. Rowland, F. Kolodgie, P.W. Serruys, R. Virmani, H.J. Duckers, Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model. Eur. Heart J. 33, 120–128 (2012)

    PubMed  CAS  Google Scholar 

  195. E. Fuchs, T. Tumbar, G. Guasch, Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778 (2004)

    PubMed  CAS  Google Scholar 

  196. M.F. Brizzi, G. Tarone, P. Defilippi, Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr. Opin. Cell Biol. 24, 645–651 (2012)

    PubMed  CAS  Google Scholar 

  197. K.H. Nakayama, C.A. Batchelder, C.I. Lee, A.F. Tarantal, Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng. Part A 16, 2207–2216 (2010)

    PubMed  CAS  Google Scholar 

  198. H. Sekiguchi, M. Ii, D.W. Losordo, The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia. J. Cell. Physiol. 219, 235–242 (2009)

    PubMed  CAS  Google Scholar 

  199. D.W. Losordo, R.A. Schatz, C.J. White, J.E. Udelson, V. Veereshwarayya, M. Durgin, K.K. Poh, R. Weinstein, M. Kearney, M. Chaudhry, A. Burg, L. Eaton, L. Heyd, T. Thorne, L. Shturman, P. Hoffmeister, K. Story, V. Zak, D. Dowling, J.H. Traverse, R.E. Olson, J. Flanagan, D. Sodano, T. Murayama, A. Kawamoto, K.F. Kusano, J. Wollins, F. Welt, P. Shah, P. Soukas, T. Asahara, T.D. Henry, Intramyocardial transplantation of autologous CD34 + stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115, 3165–3172 (2007)

    PubMed  Google Scholar 

  200. D. W. Losordo, T. D. Henry, C. Davidson, J. Sup Lee, M. A. Costa, T. Bass, F. Mendelsohn, F. D. Fortuin, C. J. Pepine, J. H. Traverse, D. Amrani, B. M. Ewenstein, N. Riedel, K. Story, K. Barker, T. J. Povsic, R. A. Harrington, R. A. Schatz, A. C. Investigators, Intramyocardial, autologous CD34 + cell therapy for refractory angina. Circ. res. 109, 428–436 (2011)

  201. F.H. Seeger, T. Rasper, A. Fischer, M. Muhly-Reinholz, E. Hergenreider, D.M. Leistner, K. Sommer, Y. Manavski, R. Henschler, E. Chavakis, B. Assmus, A.M. Zeiher, S. Dimmeler, Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair. Circ. Res. 111, 854–862 (2012)

    PubMed  CAS  Google Scholar 

  202. L.G. Melo, A.S. Pachori, D. Kong, M. Gnecchi, K. Wang, R.E. Pratt, V.J. Dzau, Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism. Circ. 109, 2386–2393 (2004)

    Google Scholar 

  203. M. Takahashi, T.S. Li, R. Suzuki, T. Kobayashi, H. Ito, Y. Ikeda, M. Matsuzaki, K. Hamano, Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am. J. Physiol. Heart Circ. Physiol. 291, 886–893 (2006)

    Google Scholar 

  204. R. Bassi, A. Trevisani, S. Tezza, M. Ben Nasr, F. Gatti, A. Vergani, A. Farina, P. Fiorina, Regenerative therapies for diabetic microangiopathy. Exp. Diabetes Res. 2012, 916560 (2012)

    PubMed  Google Scholar 

  205. C.E. Glass, P.K. Singal, D.K. Singla, Stem cells in the diabetic infarcted heart. Heart Fail. Rev. 15, 581–588 (2010)

    PubMed  Google Scholar 

  206. A.R. Williams, J.M. Hare, Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ. Res. 109, 923–940 (2011)

    PubMed  CAS  Google Scholar 

  207. S.L. Chen, W.W. Fang, F. Ye, Y.H. Liu, J. Qian, Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction. Am. J. Cardiol. 94, 92–95 (2004)

    PubMed  Google Scholar 

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Acknowledgments

We thank G. Togliatto and P. Dentelli for their useful advices. This work was supported by Grants obtained by MFB from the Italian Association for Cancer Research (AIRC) and from Ministero dell’Università e della Ricerca Scientifica (MIUR) progetto PRIN.

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Correspondence to Maria Felice Brizzi.

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Maddalena Gili and Alberto Orsello equally contributed to the study.

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Gili, M., Orsello, A., Gallo, S. et al. Diabetes-associated macrovascular complications: cell-based therapy a new tool?. Endocrine 44, 557–575 (2013). https://doi.org/10.1007/s12020-013-9936-8

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