Stem cell and progenitor cell therapy in peripheral artery disease: A critical appraisal

Thrombosis and Haemostasis

Volumn 103, Issue 4, 2010, Pages 696-709

  Lawall, Holger ^a   Bramlage, Peter ^b   Amann, Berthold ^c  

^a Klinikum Karlsbad Langensteinbach   (Germany)

^b Institute for Cardiovascular Pharmacology und Epidemiology   (Germany)

^c MARTIN LUTHER KRANKENHAUS   (Germany)

Author keywords

Angiogenesis; Bone marrow transplantation; Critical limb ischaemia; Peripheral arterial disease; Progenitor cell therapy

Indexed keywords

GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR;

ANALGESIA; ANGIOGENESIS; ANIMAL MODEL; ANKLE BRACHIAL INDEX; ATHEROSCLEROSIS; AUTOLOGOUS STEM CELL TRANSPLANTATION; CAPILLARY PROLIFERATION; CELL FUNCTION; CELL SEPARATION; CELL TYPE; CLINICAL RESEARCH; CLINICAL TRIAL; COLLATERAL CIRCULATION; HEMATOPOIETIC STEM CELL; HUMAN; LEG AMPUTATION; LEG ISCHEMIA; LEG PAIN; LIMB ISCHEMIA; LIMB SALVAGE; NONHUMAN; OXYGEN TENSION; PATIENT SAFETY; PERIPHERAL BLOOD MONONUCLEAR CELL; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRIORITY JOURNAL; REVASCULARIZATION; REVIEW; STEM CELL TRANSPLANTATION; WOUND HEALING;

ANIMALS; COLLATERAL CIRCULATION; CRITICAL ILLNESS; DISEASE MODELS, ANIMAL; EVIDENCE-BASED MEDICINE; HUMANS; ISCHEMIA; LOWER EXTREMITY; MICROCIRCULATION; NEOVASCULARIZATION, PHYSIOLOGIC; PERIPHERAL VASCULAR DISEASES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECOVERY OF FUNCTION; REGENERATIVE MEDICINE; REGIONAL BLOOD FLOW; STEM CELL TRANSPLANTATION; TIME FACTORS; TRANSPLANTATION, AUTOLOGOUS; TREATMENT OUTCOME;

EID: 77952263979     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH09-10-0688     Document Type: Review

References (149)

1. Olin JW. Thromboangiitis obliterans (Buerger's disease). N Engl J Med 2000; 343: 864-869.
2. Ness J, Aronow WS. Prevalence of coexistence of coronary artery disease, ischemic stroke, and peripheral arterial disease in older persons, mean age 80 years, in an academic hospital-based geriatrics practice. J Am Geriatr Soc 1999; 47: 1255-1256. (Pubitemid 29473300)
3. Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 2005; 366: 1925-1934.
4. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology
5. Hershey JC, Baskin EP, Glass JD, et al. Revascularization in the rabbit hindlimb: dissociation between capillary sprouting and arteriogenesis. Cardiovasc Res 2001; 49: 618-625.
6. Ito WD, Arras M, Scholz D, et al. Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion. Am J Physiol 1997; 273: H1255-H1265. (Pubitemid 27418824)
7. Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol 2006; 59: 15-26.
8. Buschmann I, Schaper W. The pathophysiology of the collateral circulation (arteriogenesis). J Pathol 2000; 190: 338-342.
9. Heilmann C, Beyersdorf F, Lutter G. Collateral growth: cells arrive at the construction site. Cardiovasc Surg 2002; 10: 570-578. (Pubitemid 35365870)
10. Diehm C, Trampisch H, Haberl R, et al. Prognosis of patients with asymptomatic versus symptomatic peripheral arterial disease (PAD): 3-year results of the getABI study. Vasc Med 2007; 12: 141-148.
11. Schirmer SH, van Nooijen FC, Piek JJ, et al. Stimulation of collateral artery growth: travelling further down the road to clinical application. Heart 2009; 95: 191-197.
12. Schaper W. Collateral circulation: past and present. Basic Res Cardiol 2009; 104: 5-21.
13. Unthank JL, Sheridan KM, Dalsing MC. Collateral growth in the peripheral circulation: a review. Vasc Endovascular Surg 2004; 38: 291-313.
14. Pipp F, Boehm S, Cai WJ, et al. Elevated fluid shear stress enhances postocclusive collateral artery growth and gene expression in the pig hind limb. Arterioscler Thromb Vasc Biol 2004; 24: 1664-1668. (Pubitemid 39180892)
15. Schierling W, Troidl K, Troidl C, Schmitz-Rixen T, Schaper W, Eitenmuller IK. The role of angiogenic growth factors in arteriogenesis. J Vasc Res 2009; 46: 365-374.
16. Heil M, Eitenmuller I, Schmitz-Rixen T, et al. Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med 2006; 10: 45-55. (Pubitemid 44874291)
17. Chappell DC, Varner SE, Nerem RM, et al. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res 1998; 82: 532-539.
18. Ziegelhoeffer T, Fernandez B, Kostin S, et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 2004; 94: 230-238. (Pubitemid 38197456)
19. Kinnaird T, Stabile E, Burnett MS, et al. Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences. Circ Res 2004; 95: 354-363. (Pubitemid 39100453)
20. Heil M, Ziegelhoeffer T, Mees B, et al. A different outlook on the role of bone marrow stem cells in vascular growth: bone marrow delivers software not hardware. Circ Res 2004; 94: 573-574. (Pubitemid 38387738)
21. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967. (Pubitemid 27087709)
22. Rohde E, Malischnik C, Thaler D, et al. Blood monocytes mimic endothelial progenitor cells. Stem Cells 2006; 24: 357-367. (Pubitemid 44464805)
23. Rehman J, Li J, Orschell CM, et al. Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107: 1164-1169.
24. Egan CG, Caporali F, Huqi AF, et al. Reduced levels of putative endothelial progenitor and CXCR4+ cells in coronary artery disease: kinetics following percutaneous coronary intervention and association with clinical characteristics. Thromb Haemost 2009; 101: 1138-1146.
25. Smadja DM, Godier A, Susen S, et al. Endothelial progenitor cells are selectively mobilised immediately after coronary artery bypass grafting or valve surgery. Thromb Haemost 2009; 101: 983-985.
26. Dimmeler S, Leri A. Aging and disease as modifiers of efficacy of cell therapy. Circ Res 2008; 102: 1319-1330.
27. Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004; 53: 195-199.
28. Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002; 106: 2781-2786.
29. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001; 89: E1-E7.
30. Kondo T, Hayashi M, Takeshita K, et al. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol 2004; 24: 1442-1447. (Pubitemid 39050438)
31. Imanishi T, Hano T, Sawamura T, et al. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol 2004; 31: 407-413. (Pubitemid 39044118)
32. Zhu S, Liu X, Li Y, et al. Aging in the atherosclerosis milieu may accelerate the consumption of bone marrow endothelial progenitor cells. Arterioscler Thromb Vasc Biol 2007; 27: 113-119. (Pubitemid 46360387)
33. Shintani S, Murohara T, Ikeda H, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103: 2776-2779. (Pubitemid 32550062)
34. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5: 434-438. (Pubitemid 29180584)
35. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circulation Res 1999; 85: 221-228. (Pubitemid 29377293)
36. Kamihata H, Matsubara H, Nishiue T, et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 2001; 104: 1046-1052. (Pubitemid 32803883)
37. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000; 97: 3422-3427. (Pubitemid 30183318)
38. Gulati R, Simari RD. Defining the potential for cell therapy for vascular disease using animal models. Dis Model Mech 2009; 2: 130-137.
39. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360: 427-435.
40. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 1913-1918. (Pubitemid 35176294)
41. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26: 517-538. (Pubitemid 27408567)
42. Timmermans F, Plum J, Yoder MC, et al. Endothelial progenitor cells: identity defined? J Cell Mol Med 2009; 13: 87-102.
43. Timmermans F, Van HF, De SM, et al. Endothelial outgrowth cells are not derived from CD133+ cells or CD45+ hematopoietic precursors. Arterioscler Thromb Vasc Biol 2007; 27: 1572-1579. (Pubitemid 46986112)
44. Purhonen S, Palm J, Rossi D, et al. Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth. Proc Natl Acad Sci USA 2008; 105: 6620-6625. (Pubitemid 351754556)
45. Canizo MC, Lozano F, Gonzalez-Porras JR, et al. Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. Cytotherapy 2007; 9: 99-102. (Pubitemid 46992970)
46. Kudo FA, Nishibe T, Nishibe M, et al. Autologous transplantation of peripheral blood endothelial progenitor cells (CD34+) for therapeutic angiogenesis in patients with critical limb ischemia. Int Angiol 2003; 22: 344-348. (Pubitemid 38324801)
47. Iohara K, Zheng L, Wake H, et al. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp. Stem Cells 2008; 26: 2408-2418.
48. Sanz-Ruiz R, Fernandez-Santos E, Dominguez-Munoa M, et al. Early translation of adipose-derived cell therapy for cardiovascular disease. Cell Transplant 2009; 18: 245-254.
49. Murphy MP, Wang H, Patel AN, et al. Allogeneic endometrial regenerative cells: an "Off the shelf solution" for critical limb ischemia? J Transl Med 2008; 6: 45.
50. Huang YC, Yang ZM, Chen XH, et al. Isolation of Mesenchymal Stem Cells from Human Placental Decidua Basalis and Resistance to Hypoxia and Serum Deprivation. Stem Cell Rev Rep 2009; prepub online doi:10.1007s12015-009-09069.
51. Finney MR, Greco NJ, Haynesworth SE, et al. Direct comparison of umbilical cord blood versus bone marrow-derived endothelial precursor cells in mediating neovascularization in response to vascular ischemia. Biol Blood Marrow Transplant 2006; 12: 585-593.
52. Boyum A. Separation of lymphocytes, lymphocyte subgroups and monocytes: a review. Lymphology 1977; 10: 71-76. (Pubitemid 8098548)
53. Boyum A. Separation of lymphocytes, granulocytes, and monocytes from human blood using iodinated density gradient media. Methods Enzymol 1984; 108: 88-102. (Pubitemid 15215616)
54. Boyum A, Lovhaug D, Tresland L, et al. Separation of leucocytes: improved cell purity by fine adjustments of gradient medium density and osmolality. Scand J Immunol 1991; 34: 697-712.
55. Boyum A, Brincker FH, Martinsen I, et al. Separation of human lymphocytes from citrated blood by density gradient (NycoPrep) centrifugation: monocyte depletion depending upon activation of membrane potassium channels. Scand J Immunol 2002; 56: 76-84. (Pubitemid 35304378)
56. Prochazka V, Gumulec J, Chmelova J, et al. Autologous bone marrow stem cell transplantation in patients with end-stage chronical critical limb ischemia and diabetic foot. Vnitr Lek 2009; 55: 173-178.
57. Amann B, Luedemann C, Ratei R, et al. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant 2009; 18: 371-380.
58. Lenk K, Adams V, Lurz P, et al. Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur Heart J 2005; 26: 1903-1909. (Pubitemid 41253304)
59. Gastens MH, Goltry K, Prohaska W, et al. Good manufacturing practice-compliant expansion of marrow-derived stem and progenitor cells for cell therapy. Cell Transplant 2007; 16: 685-696. (Pubitemid 351448264)
60. Hermann PC, Huber SL, Herrler T, et al. Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity. Cell Transplant 2008; 16: 1059-1069. (Pubitemid 351732848)
61. Kawamura A, Horie T, Tsuda I, et al. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. J Artif Organs 2006; 9: 226-233. (Pubitemid 44954312)
62. Huang PP, Yang XF, Li SZ, et al. Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow-mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thromb Haemost 2007; 98: 1335-1342.
63. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004; 44: 1690-1699. (Pubitemid 39369805)
64. Hernandez P, Cortina L, Artaza H, et al. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis 2007; 194: e52-e56. (Pubitemid 47513071)
65. Seeger FH, Tonn T, Krzossok N, et al. Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J 2007; 28: 766-772. (Pubitemid 46439231)
66. Janssens S, Dubois C, Bogaert J, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006; 367: 113-121. (Pubitemid 43077127)
67. Schachinger V, Erbs S, Elsasser A, et al. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 2006; 27: 2775-2783. (Pubitemid 44871463)
68. Sprengers RW, Lips DJ, Moll FL, et al. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg 2008; 247: 411-420.
69. Higashi Y, Kimura M, Hara K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004; 109: 1215-1218. (Pubitemid 38372778)
70. Durdu S, Akar AR, Arat M, et al. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg 2006; 44: 732-739. (Pubitemid 44441783)
71. Saigawa T, Kato K, Ozawa T, et al. Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells. Circ J 2004; 68: 1189-1193. (Pubitemid 40018866)
72. Gyongyosi M, Lang I, Dettke M, et al. Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study. Nat Clin Pract Cardiovasc Med 2009; 6: 70-81.
73. Honold J, Lehmann R, Heeschen C, et al. Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 2006; 26: 2238-2243. (Pubitemid 44465717)
74. Dreger P, Schmitz N. Stem Cell Mobilization in Healthy Donors: Current Status. Infusionstherapie und Transfusionsmedizin 1999; 26: 92-95. (Pubitemid 29185839)
75. Johnsen HE. Clinical practice and future needs in recombinant human granulocyte colony-stimulating factor treatment: a review of randomized trials in clinical haemato-oncology. J Int Med Res 2001; 29: 87-99.
76. Buschmann IR, Hoefer IE, van Royen N, et al. GM-CSF: a strong arteriogenic factor acting by amplification of monocyte function. Atherosclerosis 2001; 159: 343-356.
77. Terrovitis J, Charitos C, Dolou P, et al. No effect of stem cell mobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction. Basic Res Cardiol 2004; 99: 241-246. (Pubitemid 38931227)
78. Huang P, Li S, Han M, et al. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005; 28: 2155-2160. (Pubitemid 41242461)
79. Shi Q, Hodara V, Butler SD, et al. Differential bone marrow stem cell mobilization by G-CSF injection or arterial ligation in baboons. J Cell Mol Med 2008; 13: 1896-1906.
80. Assmus B, Schachinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 2002; 106: 3009-3017. (Pubitemid 35440281)
81. Thompson CA, Reddy VK, Srinivasan A, et al. Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells. J Heart Lung Transplant 2005; 24: 1385-1392. (Pubitemid 41247826)
82. Zhang M, Methot D, Poppa V, et al. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 2001; 33: 907-921. (Pubitemid 32545326)
83. Tran N, Li Y, Maskali F, et al. Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium. Cell Transplant 2006; 15: 351-358. (Pubitemid 44162647)
84. Amann B, Ludemann C, Ruckert R, et al. Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI). VASA 2008; 37: 319-325.
85. Yoshida M, Horimoto H, Mieno S, et al. Intra-arterial bone marrow cell transplantation induces angiogenesis in rat hindlimb ischemia. Eur Surg Res 2003; 35: 86-91. (Pubitemid 36407917)
86. Bartsch T, Brehm M, Zeus T, et al. Autologous mononuclear stem cell transplantation in patients with peripheral occlusive arterial disease. J Cardiovasc Nurs 2006; 21: 430-432.
87. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 1913-1918. (Pubitemid 35176294)
88. Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 2005; 115: 572-583. (Pubitemid 40322227)
89. Bartsch T, Brehm M, Zeus T, et al. Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (the TAMPAD study). Clin Res Cardiol 2007; 96: 891-899. (Pubitemid 350164931)
90. Van Tongeren RB, Hamming JF, Fibbe WE, et al. Intramuscular or combined intramuscular/ intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J Cardiovasc Surg 2008; 49: 51-58.
91. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circulation Res 2001; 89: E1-E7.
92. Fadini GP, Sartore S, Albiero M, et al. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 2006; 26: 2140-2146. (Pubitemid 44253800)
93. Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 2004; 109: 1615-1622. (Pubitemid 38451717)
94. Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108: 391-397. (Pubitemid 32730785)
95. Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone marrow - derived endothelial progenitor cells. J Clin Invest 2001; 108: 399-405. (Pubitemid 32730786)
96. Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001; 103: 2885-2890. (Pubitemid 32578123)
97. Assmus B, Urbich C, Aicher A, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circulation Res 2003; 92: 1049-1055. (Pubitemid 36588505)
98. Shantsila E, Watson T, Lip GY. Endothelial progenitor cells in cardiovascular disorders. J Am Coll Cardiol 2007; 49: 741-752. (Pubitemid 46251466)
99. Pistrosch F, Herbrig K, Oelschlaegel U, et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells. Atherosclerosis 2005; 183: 163-167. (Pubitemid 41416835)
100. Wang CH, Ting MK, Verma S, et al. Pioglitazone increases the numbers and improves the functional capacity of endothelial progenitor cells in patients with diabetes mellitus. Am Heart J 2006; 152: 1051-1058. (Pubitemid 44854808)
101. Di Stefano R., Barsotti MC, Melillo E, et al. The prostacyclin analogue iloprost increases circulating endothelial progenitor cells in patients with critical limb ischemia. Thromb Haemost 2008; 100: 871-877.
102. Wadhwa M, Thorpe R. Haematopoietic growth factors and their therapeutic use. Thromb Haemost 2008; 99: 863-873. (Pubitemid 351705302)
103. Akita T, Murohara T, Ikeda H, et al. Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Lab Invest 2003; 83: 65-73. (Pubitemid 36126051)
104. Sasaki K, Heeschen C, Aicher A, et al. 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 USA 2006; 103: 14537-14541. (Pubitemid 44484785)
105. Iwaguro H, Yamaguchi J, Kalka C, et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002; 105: 732-738. (Pubitemid 34157378)
106. Yi C, Xia W, Zheng Y, et al. Transplantation of endothelial progenitor cells transferred by vascular endothelial growth factor gene for vascular regeneration of ischemic flaps. J Surg Res 2006; 135: 100-106. (Pubitemid 44215901)
107. Choi JH, Hur J, Yoon CH, et al. Augmentation of therapeutic angiogenesis using genetically modified human endothelial progenitor cells with altered glycogen synthase kinase-3beta activity. J Biol Chem 2004; 279: 49430-49438.
108. Miyamoto K, Nishigami K, Nagaya N, et al. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation 2006; 114: 2679-2684. (Pubitemid 44967352)
109. Matoba S, Tatsumi T, Murohara T, et al. 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 2008; 156: 1010-1018.
110. Iba O, Matsubara H, Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation 2002; 106: 2019-2025. (Pubitemid 35176311)
111. Kinnaird T, Stabile E, Burnett MS, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109: 1543-1549. (Pubitemid 38420184)
112. Kinnaird T, Stabile E, Burnett MS, et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circulation Res 2004; 94: 678-685. (Pubitemid 38387752)
113. Niagara MI, Haider HK, Ye L, et al. Autologous skeletal myoblasts transduced with a new adenoviral bicistronic vector for treatment of hind limb ischemia. J Vasc Surg 2004; 40: 774-785. (Pubitemid 39311647)
114. Napoli C, Williams-Ignarro S, de Nigris F, et al. Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb. Proc Natl Acad Sci USA 2005; 102: 17202-17206. (Pubitemid 41692707)
115. Takagi Y, Omura T, Yoshiyama M, et al. Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia. J Pharmacol Sci 2005; 99: 45-51. (Pubitemid 41366889)
116. Iwase T, Nagaya N, Fujii T, et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res 2005; 66: 543-551. (Pubitemid 40725766)
117. Nakagami H, Maeda K, Morishita R, et al. Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells. Arterioscler Thromb Vasc Biol 2005; 25: 2542-2547. (Pubitemid 43732276)
118. Yoon KH, Lee JH, Kim JW, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006; 368: 1681-1688. (Pubitemid 46048556)
119. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation 2006; 114: 2823-2830. (Pubitemid 46018285)
120. Awad O, Dedkov EI, Jiao C, et al. Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol 2006; 26: 758-764.
121. Kobayashi K, Kondo T, Inoue N, et al. Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis. Arterioscler Thromb Vasc Biol 2006; 26: 1465-1472. (Pubitemid 44288970)
122. Li S, Zhou B, Han ZC. Therapeutic neovascularization by transplantation of mobilized peripheral blood mononuclear cells for limb ischemia. A comparison between CD34+ and. Thromb Haemost 2006; 95: 301-311.
123. Kim SW, Han H, Chae GT, et al. Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger's disease and ischemic limb disease animal model. Stem Cells 2006; 24: 1620-1626. (Pubitemid 44464680)
124. Moon MH, Kim SY, Kim YJ, et al. Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem 2006; 17: 279-290.
125. Sica V, Williams-Ignarro S, de Nigris F, et al. Autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the diabetic mouse hindlimb. Cell Cycle 2006; 5: 2903-2908. (Pubitemid 44953945)
126. Jeon O, Song SJ, Bhang SH, et al. Additive effect of endothelial progenitor cell mobilization and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs. J Biomed Sci 2007; 14: 323-330. (Pubitemid 46855420)
127. Zhang H, Zhang N, Li M, et al. Therapeutic angiogenesis of bone marrow mononuclear cells (MNCs) and peripheral blood MNCs: transplantation for ischemic hindlimb. Ann Vasc Surg 2008; 22: 238-247.
128. Esato K, Hamano K, Li TS, et al. Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease. Cell Transplant 2002; 11: 747-752. (Pubitemid 36176786)
129. Saigawa T, Kato K, Ozawa T, et al. Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells. Circ J 2004; 68: 1189-1193. (Pubitemid 40018866)
130. Higashi Y, Kimura M, Hara K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004; 109: 1215-1218. (Pubitemid 38372778)
131. Miyamoto M, Yasutake M, Takano H, et al. Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy. Cell Transplant 2004; 13: 429-437. (Pubitemid 39163088)
132. Nizankowski R, Petriczek T, Skotnicki A, et al. The treatment of advanced
133. Durdu S, Akar AR, Arat M, et al. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg 2006; 44: 732-739. (Pubitemid 44441783)
134. Bartsch T, Falke T, Brehm M, et al. Transplantation of autologous adult bone marrow stem cells in patients with severe peripheral arterial occlusion disease. Med Klin (Munich) 2006; 101 (Suppl 1): 195-197. (Pubitemid 43194538)
135. Kajiguchi M, Kondo T, Izawa H, et al. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia. Circ J 2007; 71: 196-201. (Pubitemid 46182692)
136. Huang PP, Yang XF, Li SZ, et al. Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow-mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thromb Haemost 2007; 98: 1335-1342.
137. Hernandez P, Cortina L, Artaza H, et al. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis 2007; 194: e52-e56. (Pubitemid 47513071)
138. Gu YQ, Zhang J, Guo LR, et al. Transplantation of autologous bone marrow mononuclear cells for patients with lower limb ischemia. Chin Med J (Engl) 2008; 121: 963-967. (Pubitemid 351578032)
139. Chochola M, Pytlik R, Kobylka P, et al. Autologous intra-arterial infusion of bone marrow mononuclear cells in patients with critical leg ischemia. Int Angiol 2008; 27: 281-290.
140. Wester T, Jorgensen JJ, Stranden E, et al. Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study. Scand J Surg 2008; 97: 56-62. (Pubitemid 351449965)
141. Van Tongeren RB, Hamming JF, Fibbe WE, et al. Intramuscular or combined intramuscular/ intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J Cardiovasc Surg 2008; 49: 51-58.
142. De Vriese AS, Billiet J, Van Droogenbroeck J, et al. Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans. J Intern Med 2008; 263: 395-403. (Pubitemid 351342677)
143. Amann B, Luedemann C, Ratei R, et al. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant 2009; 18: 371-380.
144. Huang PP, Li SZ, Han MZ, et al. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Thromb Haemost 2004; 91: 606-609.
145. Kawamura A, Horie T, Tsuda I, et al. Prevention of limb amputation in patients with limbs ulcers by autologous peripheral blood mononuclear cell implantation. Ther Apher Dial 2005; 9: 59-63. (Pubitemid 40393326)
146. Lenk K, Adams V, Lurz P, et al. Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur Heart J 2005; 26: 1903-1909. (Pubitemid 41253304)
147. Huang P, Li S, Han M, et al. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005; 28: 2155-2160. (Pubitemid 41242461)
148. Ishida A, Ohya Y, Sakuda H, et al. Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia. Circ J 2005; 69: 1260-1265. (Pubitemid 41382950)
149. Kawamura A, Horie T, Tsuda I, et al. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. J Artif Organs 2006; 9: 226-233. (Pubitemid 44954312)