Stem Cell Therapies in Peripheral Vascular Diseases — Current Status

Diana Opincariu 1 , 2 , András Mester 1 , 2 , Imre Benedek 1 , 2 ,  and István Benedek 1 , 3
  • 1 University of Medicine and Pharmacy, , Tîrgu Mureș, Romania
  • 2 Center of Advanced Research in Multimodality Cardiac Imaging, Cardio Med Medical Center, , Tîrgu Mureș, Romania
  • 3 Clinic of Hematology and Bone Marrow Transplantation Unit, , Tîrgu Mureș, Romania

Abstract

Peripheral artery diseases include all arterial diseases with the exception of coronary and aortic involvement, more specifically diseases of the extracranial carotids, upper limb arteries, mesenteric and renal vessels, and last but not least, lower limb arteries. Mononuclear stem cells, harvested from various sites (bone marrow, peripheral blood, mesenchymal cells, adipose-derived stem cells) have been studied as a treatment option for alleviating symptoms in peripheral artery disease, as potential stimulators for therapeutic angiogenesis, thus improving vascularization of the ischemic tissue. The aim of this manuscript was to review current medical literature on a novel treatment method — cell therapy, in patients with various peripheral vascular diseases, including carotid, renal, mesenteric artery disease, thromboangiitis obliterans, as well as upper and lower limb artery disease.

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  • 1. Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2017;00:1-60.

  • 2. Tendera M, Aboyans V, Bartelink ML, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32:2851-2906.

  • 3. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382:1329-1340.

  • 4. Lindgren H, Gottsäter A, Qvarfordt P, Bergman S. All Cause Chronic Widespread Pain is Common in Patients with Symptomatic Peripheral Arterial Disease and is Associated with Reduced Health Related Quality of Life. Eur J Vasc Endovasc Surg. 2016;52:205-210.

  • 5. Regensteiner JG, Hiatt WR, Coll JR. et al. The impact of peripheral arterial disease on health-related quality of life in the Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) Program. Vasc Med. 2008;13:15-24.

  • 6. Piepoli MF, Hoes WA, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37:2315-2381.

  • 7. Belcaro G, Nicolaides AN, Ramaswami G, et al. Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study). Atherosclerosis. 2001;156:379-387.

  • 8. de Weerd M, Greving JP, de Jong AW, Buskens E, Bots ML. Prevalence of asymptomatic carotid artery stenosis according to age and sex: systematic review and metaregression analysis. Stroke. 2009;40:1105-1113.

  • 9. Razzouk L, Rockman CB, Patel MR, et al. Co-existence of vascular disease in different arterial beds: peripheral artery disease and carotid artery stenosis—data from Life Line ScreeningVR. Atherosclerosis. 2015;241:687-691.

  • 10. McCarthy WJ, Flinn WR, Yao JS, Williams LR, Bergan JJ. Result of bypass grafting for upper limb ischemia. J Vasc Surg. 1986;3:741-746.

  • 11. Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl J Med. 2000;343:864-869.

  • 12. Papa M, Bass A, Adar R, et al. Autoimmune mechanisms in thromboangiitis obliterans (Buerger’s disease): the role of tobacco antigen and the major histocompatibility complex. Surgery. 1992;111:527-531.

  • 13. Widminsky P, Kohl P, Agewall S, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) – Web Addenda. Eur Heart J. 2017;00:1-22.

  • 14. Shadman R, Criqui MH, Bundens WP, et al. Subclavian artery stenosis: prevalence, risk factors, and association with cardiovascular diseases. J Am Coll Cardiol. 2004;44:618-623.

  • 15. Potter BJ, Pinto DS. Subclavian steal syndrome. Circulation. 2014;129:2320-2323.

  • 16. Saha T, Naqvi SY, Ayah OA, et al. Subclavian Artery Disease: Diagnosis and Therapy. Am J Med. 2017;130:409-416.

  • 17. Liew NC, Lee L, Nor Hanipah Z, et al. Pathogenesis and Management of Buerger's Disease. Int J Low Extrem Wounds. 2015;14:231-235.

  • 18. Bageacu S, Cerisier A, Isaaz K, Nourissat A, Barral X, Favre JP. Incidental visceral and renal artery stenosis in patients undergoing coronary angiography. Eur J Vasc Endovasc Surg. 2011;41:385-390.

  • 19. Hansen KJ1, Edwards MS, Craven TE, et al. Prevalence of renovascular disease in the elderly: a population-based study. J Vasc Surg. 2002;36:443-451.

  • 20. Rokni N, Salarifar M, Hakki Kazazi E, Goodarzynejad H. Frequency and Predictors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Catheterization. J Teh Univ Heart Ctr. 2012;7:58-64.

  • 21. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382:1329-1340.

  • 22. Patel MR, Conte MS, Cutlip DE, et al. Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from Peripheral Academic Research Consortium (PARC). J Am Coll Cardiol. 2015;65:931-941.

  • 23. Dua A, Lee CJ. Epidemiology of Peripheral Arterial Disease and Critical Limb Ischemia. Tech Vasc Interv Radiol. 2016;19:91-95.

  • 24. Varu VN, Hogg ME, Kibbe MR. Critical limb ischemia. J Vasc Surg. 2010;51:230-241.

  • 25. Abu Dabrh AM, Steffen MW, Undavalli C, et al. The natural history of untreated severe or critical limb ischemia. J Vasc Surg. 2015;62:1642-1651.

  • 26. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Intersociety consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45:S5-S67.

  • 27. Criqui MH, Aboyans V. Epidemiology of Peripheral Artery Disease. Circ Res. 2015;116:1509-1526.

  • 28. Lawall H, Bramlage P, Amann B. Treatment of peripheral arterial disease using stem and progenitor cell therapy. J Vasc Surg. 2011;53:445-453.

  • 29. Botham CM, Bennett WL, Cooke JP. Clinical trials of adult stem cell therapy for peripheral artery disease. Methodist Debakey Cardiovasc J. 2013;9:201-205.

  • 30. Hirota K, Semenza GL. Regulation of angiogenesis by hypoxiainducible factor 1. Crit Rev Oncol Hematol. 2006;59:15-26.

  • 31. Voskuil M, van Royen N, Hoefer I, Buschmann I, Schaper W, Piek JJ. Angiogenesis and arteriogenesis; the long road from concept to clinical application. Ned Tijdschr Geneeskd. 2001;145:670-675.

  • 32. Buschmann I, Schaper W. The pathophysiology of the collateral circulation (arteriogenesis). J Pathol. 2000;190:338-342.

  • 33. Heilmann C, Beyersdorf F, Lutter G. Collateral growth: cells arrive at the construction site. Cardiovasc Surg. 2002;10:570-578.

  • 34. Heil M, Ziegelhoeffer T, Mees B, Schaper W. 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.

  • 35. Kinnaird T, Stabile E, Burnett MS, Epstein SE. Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences. Circ Res. 2004;95:354-363.

  • 36. Jin DK, Shido K, Kopp HG, et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4_hemangiocytes. Nat Med. 2006;12:557-567.

  • 37. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964-967.

  • 38. Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164-1169.

  • 39. Imanishi T, Hano T, Sawamura T, Nishio I. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol. 2004;31:407-413.

  • 40. 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.

  • 41. 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.

  • 42. 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.

  • 43. Zhu S, Liu X, Li Y, Goldschmidt-Clermont PJ, Dong C. Aging in the atherosclerosis milieu may accelerate the consumption of bone marrow endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2007;27:113-119.

  • 44. Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. Thromb Haemost. 2010;103:696-709.

  • 45. Sen S, McDonald SP, Coates PT, Bonder CS. Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin Sci (Lond). 2011;120:263-283.

  • 46. Barber CL, Iruela-Arispe ML. The ever-elusive endothelial progenitor cell: identities, functions and clinical implications. Pediatr Res. 2006;59:26-32.

  • 47. Cañizo MC, Lozano F, González-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.

  • 48. Kudo FA, Nishibe T, Nishibe M, Yasuda K. Autologous transplantation of peripheral blood endothelial progenitor cells (CD34_) for therapeutic angiogenesis in patients with critical limb ischemia. Int Angiol. 2003;22:344-348.

  • 49. Misra V, Lal A, Khouri RE, Chen PR, Savitz SI. Intra-Arterial Delivery of Cell Therapies for Stroke. Stem Cells Dev. 2012;21:1007-1015.

  • 50. Savitz SI, Misra V, Kasam M, et al. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol. 2011;70:59-69.

  • 51. Battistella V, de Freitas GR, da Fonseca LM, et al. Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen Med. 2011;6:45-52.

  • 52. Kamiya N, Ueda M, Igarashi H, et al. Intra-arterial transplantation of bone marrow mononuclear cells immediately after reperfusion decreases brain injury after focal ischemia in rats. Life Sci. 2008;83:433-437.

  • 53. Li Y, Chopp M, Chen J, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000;20:1311-1319.

  • 54. Moniche F, Gonzalez A, Gonzalez-marcos J-R, et al. Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke. 2012;43:2242-2244.

  • 55. Wang QR, Wang BH, Huang YH, Dai G, Li WM, Yan Q. Purification and growth of endothelial progenitor cells from murine bone marrow mononuclear cells. J Cell Biochem. 2008;103:21-29.

  • 56. Kim H, Park J, Choi YJ, et al. Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy. Stem Cells. 2009;27:1686-1696.

  • 57. Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001;105:369-377.

  • 58. Kumar A, Prasad M, Jali VP, et al. Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review. Acta Neurol Scand. 2017;135:496-506.

  • 59. Jeong H, Yim HW, Cho YS, et al. Efficacy and safety of stem cell therapies for patients with stroke: a systematic review and single arm meta-analysis. Int J Stem Cells. 2014;7:63-69.

  • 60. Bhasin A, Srivastava M, Bhatia R, Mohanty S, Kumaran S, Bose S. Autologous intravenous mononuclear stem cell therapy in chronic ischemic stroke. J Stem Cells Regen Med. 2012;8:181-189.

  • 61. Banerjee S, Bentley P, Hamady M, et al. Intra-arterial immunoselected CD34+ stem cells for acute ischemic stroke. Stem Cells Transl Med. 2014;3:1322-1330.

  • 62. Lees JS, Sena ES, Egan KJ, et al. Stem cell-based therapy for experimental stroke: a systematic review and meta-analysis. Int J Stroke. 2012;7:582-588.

  • 63. Janowski M, Walczak P, Date I. Intravenous route of cell delivery for treatment of neurological disorders: a meta-analysis of preclinical results. Stem Cells Dev. 2010;19:5-16.

  • 64. Willing AE, Lixian J, Milliken M, et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res. 2003;73:296-307.

  • 65. Yang B, Migliati E, Parsha K, et al. Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke. Stroke. 2013;44:3463-3472.

  • 66. Bharadvaj BK, Mabon RF, Giddens DP. Steady flow in a model of the human carotid bifurcation. Part I—flow visualization. J Biomech. 1982;15:349-362.

  • 67. Tanriover N, Kawashima M, Rhoton AL Jr, et al. Microsurgical anatomy of the early branches of the middle cerebral artery: morphometric analysis and classification with angiographic correlation. J Neurosurg. 2003;98:1277-1290.

  • 68. Hess DC, Wechsler LR, Clark WM, et al. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16:360-368.

  • 69. Prasad K, Sharma A, Garg A, et al. Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial. Stroke. 2014;45:3618-3624.

  • 70. van Ramshorst J, Bax JJ, Beeres SL, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009;301:1997-2004.

  • 71. De Vriese AS, Billet J, Van Droogenbroeck J, Ghekiere J, De Letter JA. Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans. J Int Med. 2008;263:395-403.

  • 72. Gyöngyösi M, Hemetsberger R, Wolbank S, et al. Delayed recovery of myocardial blood flow after intracoronary stem cell administration. Stem Cell Rev. 2011;7:616-623.

  • 73. Gyöngyösi M, Wojakowski W, Lemarchand P, et al. MetaAnalysis of Cellbased CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data. Circ Res. 2015;116:1346-1360.

  • 74. Bura A, Planat-Benard V, Bourin P, et al. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with nonrevascularizable critical limb ischemia. Cytotherapy. 2014;16:245-257.

  • 75. Takagi G, Miyamoto M, Tara S, et al. Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study. Rheumatology (Oxford). 2014;53:854-859.

  • 76. Georgiadis GS, Argyriou C, Antoniou GA, et al. Upper limb vascular calcification score as a predictor of mortality in diabetic hemodialysis patients. J Vasc Surg. 2015;61:1529-1537.

  • 77. Bae M, Chung SW, Lee CW, Choi J, Song S, Kim S. Upper Limb Ischemia: Clinical Experiences of Acute and Chronic Upper Limb Ischemia in a Single Center. Korean J Thorac Cardiovasc Surg. 2015;48:246-251.

  • 78. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. 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.

  • 79. Comerota AJ, Link A, Douville J, Burchard ER. Upper extremity ischemia treated with tissue repair cells from adult bone marrow. J Vasc Surg. 2010;52:723-729.

  • 80. Koshikawa M, Shimodaira S, Yoshioka T, et al. Therapeutic angiogenesis by bone marrow implantation for critical hand ischemia in patients with peripheral arterial disease: a pilot study. Curr Med Res Opin. 2006;22:793-798.

  • 81. Nevskaya T, Ananieva L, Bykovskaia S, et al. Autologous progenitor cell implantation as a novel therapeutic intervention for ischaemic digits in systemic sclerosis. Rheumatology (Oxford). 2009;48:61-64.

  • 82. Lee KB, Kang ES, Kim AK. Stem Cell Therapy in Patients with Thromboangiitis Obliterans: Assessment of the Long-Term Clinical Outcome and Analysis of the Prognostic Factors. International Journal of Stem Cells. Int J Stem Cells. 2011;4:88-98.

  • 83. Kim DI, Kim MJ, Joh JH, et al. Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger’s disease. Stem Cells. 2006;24:1194-1200.

  • 84. Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006;44:732-739.

  • 85. 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.

  • 86. Motukuru V, Suresh KR, Vivekanand V, Raj S, Girija KR. Therapeutic angiogenesis in Buerger’s disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells. J Vasc Surg. 2008;48:53S-60S.

  • 87. Kim DI, Kim MJ, Joh JH, et al. Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger's disease. Stem Cells. 2006;24:1194-1200.

  • 88. Motukuru V, Suresh KR, Vivekanand V, et al. Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells. J Vasc Surg. 2008;48:53S-60S.

  • 89. Roussel A, Castier Y, Nuzzo A, et al. Revascularization of acute mesenteric ischemia after creation of a dedicated multidisciplinary center. J Vasc Surg. 2015;62:1251-1256.

  • 90. Markel TA, Crisostomo PR, Lahm T, et al. Stem cells as a potential future treatment of pediatric intestinal disorders. J Pediatr Surg. 2008;43:1953-1963.

  • 91. Jensen AR, Doster DL, Hunsberger EB. Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury. Shock. 2016;46:75-82.

  • 92. Inan M, Bakar E, Cerkezkayabekir A, et al. Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage. J Pediatr Surg. 2017;52:1196-1206.

  • 93. Jiang H, Qu L, Li Y, et al. Bone marrow mesenchymal stem cells reduce intestinal ischemia/reperfusion injuries in rats. J Surg Res. 2011;168:127-134.

  • 94. van Ampting JM, Penne EL, Beek FJ, et al. Prevalence of atherosclerotic renal artery stenosis in patients starting dialysis. Nephrol Dial Transplant. 2003; 18:1147-1151.

  • 95. Fatica RA, Port FK, Young EW. Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States. Am J Kidney Dis. 2001;37:1184-1190.

  • 96. Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living related kidney transplants: a randomized controlled trial. JAMA. 2012;307:1169-1177.

  • 97. Textor SC, Lerman LO. Renal artery stenosis: medical versus interventional therapy. Curr Cardiol Rep. 2013;15:409.

  • 98. Sadek EM, Afifi NM, Elfattah LI, Mohsen MA. Histological study on effect of mesenchymal stem cell therapy on experimental renal injury induced by ischemia/reperfusion in male albino rat. Int J Stem Cells. 2013;6:55-66.

  • 99. Lee P, Chien Y, Chiou G, Lin C, Chiou C, Tarng D. Induced pluripotent stem cells without c-Myc attenuate acute kidney injury via downregulating the signaling of oxidative stress and inflammation in ischemia-reperfusion rats. Cell Transplant. 2012;21:2569-2585.

  • 100. Humphreys BD, Bonventre JV. Mesenchymal stem cells in acute kidney injury. Medicine. 2008;59:311.

  • 101. Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living related kidney transplants: a randomized controlled trial. JAMA. 2012;307:1169-1177.

  • 102. Zhu XY, Lerman A, Lerman LO. Concise Review: Mesenchymal Stem Cell Treatment for Ischemic Kidney Disease. Stem Cells. 2013;31:1731-1736.

  • 103. Chade AR, Zhu X, Lavi R, et al. Endothelial progenitor cells restore renal function in chronic experimental renovascular disease. Circulation. 2009;119:547-557.

  • 104. Chade AR, Zhu XY, Krier JD, et al. Endothelial progenitor cells homing and renal repair in experimental renovascular disease. Stem Cells. 2010;28:1039-1047.

  • 105. Ebrahimi B, Eirin A, Li Z, et al. Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis. PLos One. 2013;8:e67474.

  • 106. Eirin A, Zhu XY, Krier JD, et al. Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis. Stem Cells. 2012;30:1030-1041.

  • 107. Saad A, Dietz AB, Herrmann SMS, et al. Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease. J Am Soc Nephrol. 2017;28:2777-2785.

  • 108. Benedek T, Kovács I, Benedek I. Therapeutic Angiogenesis for Severely Ischemic Limbs — from Bench to Bedside in Acute Vascular Care. Journal of Cardiovascular Emergencies. 2017;3:160-171.

  • 109. Kum S, Tan YK, Schreve MA, et al. Midterm Outcomes From a Pilot Study of Percutaneous Deep Vein Arterialization for the Treatment of No-Option Critical Limb Ischemia. J Endovasc Ther. 2017; 24:619-626.

  • 110. Chen XP, Fu WM, Gu W. Spinal Cord stimulation for patients with inoperable chronic critical leg ischemia. World J Emerg Med. 2011;2:262-266.

  • 111. Compagna R, Amato B, Massa S, et al. Cell Therapy in Patients with Critical Limb Ischemia. Stem Cells Int. 2015;2015:931420.

  • 112. 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.

  • 113. Rigato M, Monami M, Fadini GP. Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies. Circ Res. 2017;120:1326-1340.

  • 114. Procházka V, Gumulec J, Jalůvka F, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplant. 2010;19:1413-1424.

  • 115. Walter DH, Krankenberg H, Balzer JO, et al. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebocontrolled pilot trial (PROVASA). Circ Cardiovasc Interv. 2011;4:26-37.

  • 116. Idei N, Soga J, Hata T, et al. Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease. Circ Cardiovasc Interv. 2011;4:15-25.

  • 117. Das AK, Bin Abdullah BJ, Dhillon SS, Vijanari A, Anoop CH, Gupta PK. Intraarterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: report of a phase I study. World J Surg. 2013;37:915-922.

  • 118. Jialal I, Devaraj S, Singh U, et al. Decreased number and impaired functionality of endothelial progenitor cells in subjects with metabolic syndrome: implications for increased cardiovascular risk. Atherosclerosis. 2010;211:297-302.

  • 119. 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.

  • 120. 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;89:1-7.

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