Intracavernous administration of bone marrow mononuclear cells: A new method of treating erectile dysfunction?

Journal of Translational Medicine

Volumn 11, Issue 1, 2013, Pages

  Ichim, Thomas E ^a   Warbington, Timothy ^b   Cristea, Octav ^c   Chin, Joseph L ^c   Patel, Amit N ^d  

^a INSTITUTE FOR MOLECULAR MEDICINE   (United States)

^b Creative Medical Health Inc   (United States)

^c UNIVERSITY OF WESTERN ONTARIO   (Canada)

^d UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; PHOSPHODIESTERASE V INHIBITOR; PROSTAGLANDIN E1; RECOMBINANT SOMATOMEDIN C;

ATHEROSCLEROSIS; AUTOTRANSPLANTATION; BONE MARROW MONONUCLEAR CELL; CELL TRANSPLANTATION; CHRONIC INFLAMMATION; CLINICAL TRIAL (TOPIC); CORPUS CAVERNOSUM; CRITICAL LIMB ISCHEMIA; CYTOKINE PRODUCTION; ENDOTHELIAL DYSFUNCTION; ENDOTHELIAL PROGENITOR CELL; ERECTILE DYSFUNCTION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; INTERNATIONAL INDEX OF ERECTILE FUNCTION; MESENCHYMAL STEM CELL TRANSPLANTATION; MICROARRAY ANALYSIS; MONONUCLEAR CELL; NONHUMAN; OUTCOME ASSESSMENT; PATIENT SAFETY; PENIS ERECTION; PROTEIN EXPRESSION; REVIEW; SEXUAL INTERCOURSE; STEM CELL MOBILIZATION; THERAPY EFFECT; TREATMENT RESPONSE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY;

ADULT; BONE MARROW CELLS; BONE MARROW TRANSPLANTATION; CYTOKINES; ENDOTHELIUM, VASCULAR; ERECTILE DYSFUNCTION; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; NEOVASCULARIZATION, PHYSIOLOGIC; PENIS; PHOSPHODIESTERASE 5 INHIBITORS;

EID: 84878647903     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/1479-5876-11-139     Document Type: Review

References (166)

1. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev 1995, 75(1):191-236.
2. Fournier GR, et al. Mechanisms of venous occlusion during canine penile erection: an anatomic demonstration. J Urol 1987, 137(1):163-167.
3. Toda N, Ayajiki K, Okamura T. Nitric oxide and penile erectile function. Pharmacol Ther 2005, 106(2):233-266. 10.1016/j.pharmthera.2004.11.011, 15866322.
4. Ravipati G, et al. Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease. Cardiol Rev 2007, 15(2):76-86. 10.1097/01.crd.0000233904.77128.49, 17303994.
5. Dussault S, et al. Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice. Hypertension 2009, 54(5):1043-1049. 10.1161/HYPERTENSIONAHA.109.139451, 19770400.
6. Foresta C, et al. The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells and CXCR4 expression. J Sex Med 2009, 6(2):369-372. 10.1111/j.1743-6109.2008.01014.x, 18823318.
7. Foresta C, et al. PDE-5 inhibitor, Vardenafil, increases circulating progenitor cells in humans. Int J Impot Res 2005, 17(4):377-380. 10.1038/sj.ijir.3901325, 15829988.
8. Foresta C, et al. Relationship between vascular damage degrees and endothelial progenitor cells in patients with erectile dysfunction: effect of vardenafil administration and PDE5 expression in the bone marrow. Eur Urol 2007, 51(5):1411-1417. discussion 1417-9, 10.1016/j.eururo.2006.08.052, 17034932.
9. Foresta C, et al. Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment. Clin Endocrinol 2009, 71(3):412-416.
10. Ferrini MG, et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 2006, 68(2):429-435. 10.1016/j.urology.2006.05.011, 16904479.
11. Kovanecz I, et al. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res 2008, 20(2):202-212. 10.1038/sj.ijir.3901612, 17882231.
12. Ozden E, et al. Effect of sildenafil citrate on penile weight and physiology of cavernous smooth muscle in a post-radical prostatectomy model of erectile dysfunction in rats. Urology 2011, 77(3):761 e1-7.
13. Padma-Nathan H, McCullough A, Forest C. Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies. Curr Urol Rep 2004, 5(6):467-471. 10.1007/s11934-004-0072-0, 15541217.
14. Sanna F, et al. Phosphodiesterase type 5 inhibitors facilitate noncontact erections in male rats: site of action in the brain and mechanism of action. J Sex Med 2009, 6(10):2680-2689. 10.1111/j.1743-6109.2009.01410.x, 19678884.
15. Hatzimouratidis K, Hatzichristou D. Phosphodiesterase type 5 inhibitors: the day after. Eur Urol 2007, 51(1):75-88. discussion 89, 10.1016/j.eururo.2006.07.020, 16949200.
16. Hatzimouratidis K, Hatzichristou DG. Phosphodiesterase type 5 inhibitors: unmet needs. Curr Pharm Des 2009, 15(30):3476-3485. 10.2174/138161209789207042, 19860693.
17. Gentile V, et al. Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes. Curr Med Res Opin 2004, 20(9):1377-1384. 10.1185/030079904X2394, 15383186.
18. Morano S, et al. Antioxidant treatment associated with sildenafil reduces monocyte activation and markers of endothelial damage in patients with diabetic erectile dysfunction: a double-blind, placebo-controlled study. Eur Urol 2007, 52(6):1768-1774. 10.1016/j.eururo.2007.04.042, 17478034.
19. Gutierrez P, Hernandez P, Mas M. Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders. Int J Impot Res 2005, 17(4):354-358. 10.1038/sj.ijir.3901290, 15703770.
20. Shabsigh R, et al. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2008, 179(5 Suppl):S97-S102.
21. Greco EA, Spera G, Aversa A. Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol 2006, 50(5):940-947. 10.1016/j.eururo.2006.06.049, 16979814.
22. Chew KK, et al. Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: findings from a linked-data study. J Sex Med 2010, 7(1 Pt 1):192-202.
23. Aversa A, et al. Endothelial dysfunction and erectile dysfunction in the aging man. International journal of urology: official journal of the Japanese Urological Association 2010, 17(1):38-47.
24. Chen SL, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 2004, 94(1):92-95. 10.1016/j.amjcard.2004.03.034, 15219514.
25. Chen SL, et al. Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction. Chin Med J 2004, 117(10):1443-1448.
26. Katritsis DG, et al. Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheterization and cardiovascular interventions: official journal of the Society for Cardiac Angiography & Interventions 2005, 65(3):321-329. 10.1002/ccd.20406, 23765522.
27. Chen S, et al. Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol 2006, 18(11):552-556.
28. Katritsis DG, et al. Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells. Europace: European pacing, arrhythmias, and cardiac electrophysiology: journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2007, 9(3):167-171.
29. Mohyeddin-Bonab M, et al. Autologous in vitro expanded mesenchymal stem cell therapy for human old myocardial infarction. Arch Iran Med 2007, 10(4):467-473.
30. Hare JM, et al. 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 2009, 54(24):2277-2286. 10.1016/j.jacc.2009.06.055, 3580848, 19958962.
31. Guhathakurta S, et al. Stem cell experiments and initial clinical trial of cellular cardiomyoplasty. Asian Cardiovasc Thorac Ann 2009, 17(6):581-586. 10.1177/0218492309349363, 20026532.
32. Lasala GP, et al. Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovascular revascularization medicine: including molecular interventions 2011, 12(1):29-34.
33. Lasala GP, et al. Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis. Angiology 2010, 61(6):551-556. 10.1177/0003319710364213, 20498146.
34. Iwase 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(3):543-551. 10.1016/j.cardiores.2005.02.006, 15914119.
35. Lu D, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: A double-blind, randomized, controlled trial. Diabetes Res Clin Pract 2011, 92(1):26-36. 10.1016/j.diabres.2010.12.010, 21216483.
36. Qiu X, et al. Combined Strategy of Mesenchymal Stem Cells Injection with VEGF Gene Therapy for the Treatment of Diabetes Associated Erectile Dysfunction. J Androl 2011, 33(1):37-44.
37. Qiu X, et al. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 2011, 8(2):427-436. 10.1111/j.1743-6109.2010.02118.x, 21091881.
38. Kendirci M, et al. Transplantation of nonhematopoietic adult bone marrow stem/progenitor cells isolated by p75 nerve growth factor receptor into the penis rescues erectile function in a rat model of cavernous nerve injury. J Urol 2010, 184(4):1560-1566. 10.1016/j.juro.2010.05.088, 3014289, 20728109.
39. Albersen M, et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med 2010, 7(10):3331-3340. 10.1111/j.1743-6109.2010.01875.x, 20561166.
40. Abdel Aziz MT, et al. Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats. Andrologia 2010, 42(3):187-192. 10.1111/j.1439-0272.2009.00977.x, 20500748.
41. Huang YC, et al. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 2010, 7(4 Pt 1):1391-1400. 3163604, 20141586.
42. Garcia MM, et al. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med 2010, 7(1 Pt 1):89-98. 2904063, 20104670.
43. Lin G, et al. Potential of adipose-derived stem cells for treatment of erectile dysfunction. J Sex Med 2009, 6(Suppl 3):320-327. 2895916, 19267855.
44. Nolazco G, et al. Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat. BJU Int 2008, 101(9):1156-1164. 10.1111/j.1464-410X.2008.07507.x, 18294308.
45. Song YS, et al. Magnetic resonance evaluation of human mesenchymal stem cells in corpus cavernosa of rats and rabbits. Asian J Androl 2007, 9(3):361-367. 10.1111/j.1745-7262.2007.00265.x, 17486277.
46. Song YS, et al. Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res 2007, 19(4):378-385. 10.1038/sj.ijir.3901539, 17460699.
47. Bivalacqua TJ, et al. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol 2007, 292(3):H1278-H1290.
48. Bochinski D, et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 2004, 94(6):904-909. 10.1111/j.1464-410X.2003.05057.x, 15476533.
49. Wespes E, Schulman CC. Erectile dysfunction and cardiovascular diseases. Arch Esp Urol 2010, 63(8):649-654.
50. Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997, 275(5302):964-967. 10.1126/science.275.5302.964, 9020076.
51. Sieveking DP, et al. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J Am Coll Cardiol 2008, 51(6):660-668. 10.1016/j.jacc.2007.09.059, 18261686.
52. Peichev M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000, 95(3):952-958.
53. Wojakowski W, Tendera M. Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes. Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society 2005, 43(4):229-232.
54. Massa M, et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood 2005, 105(1):199-206. 10.1182/blood-2004-05-1831, 15345590.
55. Voo S, et al. Enhanced functional response of CD133+ circulating progenitor cells in patients early after acute myocardial infarction. Eur Heart J 2008, 29(2):241-250.
56. Bogoslovsky T, et al. Endothelial progenitor cells correlate with lesion volume and growth in acute stroke. Neurology 2010, 75(23):2059-2062. 10.1212/WNL.0b013e318200d741, 2995536, 21135380.
57. Navarro-Sobrino M, et al. Mobilization, endothelial differentiation and functional capacity of endothelial progenitor cells after ischemic stroke. Microvasc Res 2010, 80(3):317-323. 10.1016/j.mvr.2010.05.008, 20594997.
58. Bogoslovsky T, et al. Stromal-derived factor-1[alpha] correlates with circulating endothelial progenitor cells and with acute lesion volume in stroke patients. Stroke; a journal of cerebral circulation 2011, 42(3):618-625. 10.1161/STROKEAHA.110.596007, 3693440, 23864999.
59. Sobrino T, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke; a journal of cerebral circulation 2007, 38(10):2759-2764. 10.1161/STROKEAHA.107.484386, 3693440, 23864999.
60. Schmidt-Lucke C, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005, 111(22):2981-2987. 10.1161/CIRCULATIONAHA.104.504340, 15927972.
61. Kupatt C, et al. Retroinfusion of embryonic endothelial progenitor cells attenuates ischemia-reperfusion injury in pigs: role of phosphatidylinositol 3-kinase/AKT kinase. Circulation 2005, 112(9 Suppl):I117-I122.
62. Aicher A, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003, 107(16):2134-2139. 10.1161/01.CIR.0000062649.63838.C9, 12695305.
63. Fan Y, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol 2010, 67(4):488-497. 10.1002/ana.21919, 3026588, 20437584.
64. Lam CF, et al. Transplantation of endothelial progenitor cells improves pulmonary endothelial function and gas exchange in rabbits with endotoxin-induced acute lung injury. Anesth Analg 2011, 112(3):620-627. 10.1213/ANE.0b013e3182075da4, 21233499.
65. Mao M, et al. Intravenous delivery of bone marrow-derived endothelial progenitor cells improves survival and attenuates lipopolysaccharide-induced lung injury in rats. Shock 2010, 34(2):196-204. 10.1097/SHK.0b013e3181d49457, 20090567.
66. Kahler CM, et al. Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury. Respir Res 2007, 8:50. 10.1186/1465-9921-8-50, 2000890, 17620112.
67. Elkhafif N, et al. CD133(+) human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 2011, 119(1):66-75. 10.1111/j.1600-0463.2010.02693.x, 21143528.
68. Liu F, et al. Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2009, 15(9):1092-1100.
69. Nakamura T, et al. Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model. Gastroenterology 2007, 133(1):91-107 e1. 10.1053/j.gastro.2007.03.110, 17631135.
70. Wang SH, et al. Late outgrowth endothelial cells derived from Wharton jelly in human umbilical cord reduce neointimal formation after vascular injury: involvement of pigment epithelium-derived factor. Arterioscler Thromb Vasc Biol 2009, 29(6):816-822. 10.1161/ATVBAHA.109.184739, 19342598.
71. Desouza CV, et al. Role of inflammation and insulin resistance in endothelial progenitor cell dysfunction. Diabetes 2011, 60(4):1286-1294. 10.2337/db10-0875, 3064102, 21346178.
72. Orlic D, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 2001, 98(18):10344-10349. 10.1073/pnas.181177898, 56963, 11504914.
73. Zhang L, et al. Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with d-galactosamine-induced acute liver failure. Toxicol Lett 2011, 204(1):92-99. 10.1016/j.toxlet.2011.04.016, 21550386.
74. Cho HJ, et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation 2003, 108(23):2918-2925. 10.1161/01.CIR.0000097001.79750.78, 14568896.
75. Lara-Hernandez R, et al. Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia. Ann Vasc Surg 2010, 24(2):287-294. 10.1016/j.avsg.2009.10.012, 20142004.
76. Kim DI, et al. Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger's disease. Stem Cells 2006, 24(5):1194-1200. 10.1634/stemcells.2005-0349, 16439614.
77. Mund JA, et al. Endothelial progenitor cells and cardiovascular cell-based therapies. Cytotherapy 2009, 11(2):103-113. 10.1080/14653240802714827, 19241233.
78. Franck-Lissbrant I, et al. Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats. Endocrinology 1998, 139(2):451-456. 10.1210/en.139.2.451, 9449610.
79. Sieveking DP, Chow RW, Ng MK. Androgens, angiogenesis and cardiovascular regeneration. Curr Opin Endocrinol Diabetes Obes 2010, 17(3):277-283. 10.1097/MED.0b013e3283394e20, 20389240.
80. Sieveking DP, et al. A sex-specific role for androgens in angiogenesis. J Exp Med 2010, 207(2):345-352. 10.1084/jem.20091924, 2822613, 20071503.
81. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev 2003, 24(3):313-340.
82. Yiu YF, et al. Vitamin d deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes. J Clin Endocrinol Metabol 2011, 96(5):E830-E835.
83. Kahn MB, et al. Insulin resistance impairs circulating angiogenic progenitor cell function and delays endothelial regeneration. Diabetes 2011, 60(4):1295-1303. 10.2337/db10-1080, 3064103, 21317296.
84. Li M, et al. The decrement in circulating endothelial progenitor cells (EPCs) in type 2 diabetes is independent of the severity of the hypoadiponectemia. Diabetes Metab Res Rev 2011, 27(2):185-194. 10.1002/dmrr.1159, 21294240.
85. Mieno S, et al. Effects of diabetes mellitus on VEGF-induced proliferation response in bone marrow derived endothelial progenitor cells. J Card Surg 2010, 25(5):618-625. 10.1111/j.1540-8191.2010.01086.x, 2958227, 20626511.
86. Reinhard H, et al. Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes. Diabetologia 2010, 53(10):2129-2133. 10.1007/s00125-010-1843-4, 20607514.
87. Ramunni A, et al. Effect of low-density lipoprotein apheresis on circulating endothelial progenitor cells in familial hypercholesterolemia. Blood Purif 2010, 29(4):383-389. 10.1159/000314650, 20484899.
88. Tie G, et al. Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res 2010, 47(6):519-530. 10.1159/000313879, 2945270, 20431300.
89. Rossi F, et al. HDL cholesterol is a strong determinant of endothelial progenitor cells in hypercholesterolemic subjects. Microvasc Res 2010, 80(2):274-279. 10.1016/j.mvr.2010.05.003, 20478316.
90. Pirro M, et al. Hypercholesterolemia-associated endothelial progenitor cell dysfunction. Ther Adv Cardiovasc Dis 2008, 2(5):329-339. 10.1177/1753944708094769, 19124431.
91. Cheng J, et al. Oxidized low-density lipoprotein stimulates p53-dependent activation of proapoptotic Bax leading to apoptosis of differentiated endothelial progenitor cells. Endocrinology 2007, 148(5):2085-2094. 10.1210/en.2006-1709, 17289842.
92. Croce G, et al. Nonpharmacological treatment of hypercholesterolemia increases circulating endothelial progenitor cell population in adults. Arterioscler Thromb Vasc Biol 2006, 26(5):e38-e39. 10.1161/01.ATV.0000218504.71680.b5, 16627813.
93. Heida NM, et al. Effects of obesity and weight loss on the functional properties of early outgrowth endothelial progenitor cells. J Am Coll Cardiol 2010, 55(4):357-367. 10.1016/j.jacc.2009.09.031, 20117442.
94. Tobler K, et al. Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity. Int J Obes 2010, 34(4):687-700.
95. Zenovich AG, Taylor DA. Atherosclerosis as a disease of failed endogenous repair. Frontiers in bioscience: a journal and virtual library 2008, 13:3621-3636.
96. Tousoulis D, et al. Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization: therapeutic implications for cardiovascular diseases. Atherosclerosis 2008, 201(2):236-247. 10.1016/j.atherosclerosis.2008.05.034, 18599065.
97. Kondo T, et al. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol 2004, 24(8):1442-1447. 10.1161/01.ATV.0000135655.52088.c5, 15191940.
98. Baumhakel M, et al. Circulating endothelial progenitor cells correlate with erectile function in patients with coronary heart disease. Eur Heart J 2006, 27(18):2184-2188. 10.1093/eurheartj/ehl202, 16926179.
99. Esposito K, et al. Circulating CD34+ KDR+ endothelial progenitor cells correlate with erectile function and endothelial function in overweight men. J Sex Med 2009, 6(1):107-114. 10.1111/j.1743-6109.2008.01042.x, 19170841.
100. Foresta C, et al. Increased levels of osteocalcin-positive endothelial progenitor cells in patients affected by erectile dysfunction and cavernous atherosclerosis. J Sex Med 2010, 7(2 Pt 1):751-757.
101. Shao H, et al. Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels. Stem Cells 2008, 26(5):1376-1384. 10.1634/stemcells.2007-0785, 18308946.
102. Zaruba MM, Franz WM. Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy. Expert Opin Biol Ther 2010, 10(3):321-335. 10.1517/14712590903460286, 20132055.
103. Hiasa K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004, 109(20):2454-2461. 10.1161/01.CIR.0000128213.96779.61, 15148275.
104. Ryu JK, et al. Downregulation of angiogenic factors and their downstream target molecules affects the deterioration of erectile function in a rat model of hypercholesterolemia. Urology 2006, 67(6):1329-1334. 10.1016/j.urology.2005.12.027, 16750245.
105. Xie D, et al. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med 2008, 5(9):2069-2078. 10.1111/j.1743-6109.2008.00933.x, 18637998.
106. Xie D, et al. Decreases in corporeal vascular endothelial growth factor expression precede vasoreactivity changes in cholesterol fed rabbits. J Urol 2005, 173(4):1418-1422. 10.1097/01.ju.0000149035.98638.33, 15758816.
107. De Young L, et al. Arteriogenic erectile dysfunction alters protein expression within the cavernosal tissue in an animal model. J Sex Med 2005, 2(2):199-206. 10.1111/j.1743-6109.2005.20229.x, 16422887.
108. Rajasekaran M, et al. Altered growth factor expression in the aging penis: the Brown-Norway rat model. J Androl 2002, 23(3):393-399.
109. Chang Hwang E, et al. Effects of Androgen on the Expression of Vascular Endothelial Growth Factor in the Penile Corpus Cavernosum. Urology 2011, 77(6):1381-1386. 10.1016/j.urology.2011.01.036, 21458034.
110. Wang T, et al. Alterations in angiogenic growth factors and neuronal nitric oxide synthase expression in chronic cavernosal ischemia. Int J Impot Res 2004, 16(5):403-411. 10.1038/sj.ijir.3901186, 14999219.
111. Byrne RR, et al. Vascular endothelial growth factor restores corporeal smooth muscle function in vitro. J Urol 2001, 165(4):1310-1315. 10.1016/S0022-5347(01)69890-2, 11257707.
112. Henry GD, et al. Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle relaxation in the hypercholesterolemic rabbit: a preliminary study. Int J Impot Res 2000, 12(6):334-339. 10.1038/sj.ijir.3900621, 11416837.
113. Rogers RS, et al. Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res 2003, 15(1):26-37. 10.1038/sj.ijir.3900943, 12605238.
114. Park K, et al. Intracavernosal injection of vascular endothelial growth factor improves erectile function in aged rats. Eur Urol 2004, 46(3):403-407. 10.1016/j.eururo.2004.04.032, 15306114.
115. Dall'Era JE, et al. Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model. Int J Impot Res 2008, 20(3):307-314. 10.1038/ijir.2008.1, 18273028.
116. Hsieh PS, et al. The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model. BJU Int 2003, 92(4):470-475. 10.1046/j.1464-410X.2003.04373.x, 12930443.
117. Lin CS, et al. Intracavernosal injection of vascular endothelial growth factor induces nitric oxide synthase isoforms. BJU Int 2002, 89(9):955-960. 10.1046/j.1464-410X.2002.02792.x, 12010247.
118. Musicki B, et al. Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection. Biol Reprod 2004, 70(2):282-289. 10.1095/biolreprod.103.021113, 14522830.
119. Yamanaka M, et al. Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura. J Urol 2005, 173(1):318-323. 10.1097/01.ju.0000141586.46822.44, 15592104.
120. Shirai M, et al. Vascular endothelial growth factor restores erectile function through modulation of the insulin-like growth factor system and sex hormone receptors in diabetic rat. Biochem Biophys Res Commun 2006, 341(3):755-762. 10.1016/j.bbrc.2005.12.226, 16455052.
121. Dai Q, et al. Systemic basic fibroblast growth factor induces favorable histological changes in the corpus cavernosum of hypercholesterolemic rabbits. J Urol 2003, 170(2 Pt 1):664-668.
122. Xie D, et al. Intracavernosal basic fibroblast growth factor improves vasoreactivity in the hypercholesterolemic rabbit. J Sex Med 2006, 3(2):223-232. 10.1111/j.1743-6109.2005.00174.x, 16490015.
123. Rabinovsky ED. The multifunctional role of IGF-1 in peripheral nerve regeneration. Neurol Res 2004, 26(2):204-210. 10.1179/016164104225013851, 15072640.
124. Abdel-Gawad M, Huynh H, Brock GB. Experimental chronic renal failure-associated erectile dysfunction: molecular alterations in nitric oxide synthase pathway and IGF-I system. Mol Urol 1999, 3(2):117-125.
125. Schaaf L, Stalla GK. [Endocrine changes with advancing age]. MMW Fortschr Med 2009, 151(42):43-45.
126. Probst-Hensch NM. Chronic age-related diseases share risk factors: do they share pathophysiological mechanisms and why does that matter?. Swiss Med Wkly 2010, 140:w13072.
127. Jung GW, et al. IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats. Int J Impot Res 1999, 11(5):247-259. 10.1038/sj.ijir.3900402, 10553803.
128. Pu XY, et al. Improvement in erectile dysfunction after insulin-like growth factor-1 gene therapy in diabetic rats. Asian J Androl 2007, 9(1):83-91. 10.1111/j.1745-7262.2007.00215.x, 16855763.
129. Pu XY, et al. Insulin-like growth factor-1 restores erectile function in aged rats: modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity. J Sex Med 2008, 5(6):1345-1354. 10.1111/j.1743-6109.2008.00817.x, 18355170.
130. Hinkel R, Trenkwalder T, Kupatt C. Gene therapy for ischemic heart disease. Expert Opin Biol Ther 2011, 11(6):723-737. 10.1517/14712598.2011.570749, 21434842.
131. Melman A, et al. hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial. Hum Gene Ther 2006, 17(12):1165-1176. 10.1089/hum.2006.17.1165, 17134370.
132. Ichim TE, et al. Combination stem cell therapy for heart failure. International archives of medicine 2010, 3(1):5. 10.1186/1755-7682-3-5, 3003238, 20398245.
133. Yu XY, et al. The effects of mesenchymal stem cells on c-kit up-regulation and cell-cycle re-entry of neonatal cardiomyocytes are mediated by activation of insulin-like growth factor 1 receptor. Mol Cell Biochem 2009, 332(1-2):25-32.
134. Shabbir A, et al. Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen. Am J Physiol Heart Circ Physiol 2009, 296(6):H1888-H1897. 10.1152/ajpheart.00186.2009, 2716100, 19395555.
135. Chen L, et al. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One 2008, 3(4):e1886. 10.1371/journal.pone.0001886, 2270908, 18382669.
136. Fan W, Crawford R, Xiao Y. The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization. Differentiation; research in biological diversity 2011, 81(3):181-191. 10.1016/j.diff.2010.12.003, 3707205, 23865046.
137. Jiang SY, Xie XT, Zhou JJ. [Gene profile and fibroblast growth factor 2 expression in mesenchymal stem cell from children with aplastic anemia]. Zhonghua er ke za zhi. Chinese journal of pediatrics 2009, 47(3):218-220.
138. Ichim TE, et al. Mesenchymal stem cells as anti-inflammatories: implications for treatment of Duchenne muscular dystrophy. Cell Immunol 2010, 260(2):75-82. 10.1016/j.cellimm.2009.10.006, 19917503.
139. Bae KS, et al. Neuron-like differentiation of bone marrow-derived mesenchymal stem cells. Yonsei Med J 2011, 52(3):401-412. 10.3349/ymj.2011.52.3.401, 3101055, 21488182.
140. Riordan NH, et al. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 2009, 7:29. 10.1186/1479-5876-7-29, 2679713, 19393041.
141. Zhong Z, et al. Feasibility investigation of allogeneic endometrial regenerative cells. J Transl Med 2009, 7:15. 10.1186/1479-5876-7-15, 2649897, 19232091.
142. Bahk JY, et al. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 2010, 8(2):150-160.
143. Thomas ED, et al. Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest 1959, 38:1709-1716. 10.1172/JCI103949, 444138, 13837954.
144. Kocher AA, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001, 7(4):430-436. 10.1038/86498, 11283669.
145. Fazel S, et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 2006, 116(7):1865-1877. 10.1172/JCI27019, 1483161, 16823487.
146. Orlic D. Adult bone marrow stem cells regenerate myocardium in ischemic heart disease. Ann N Y Acad Sci 2003, 996:152-157. 10.1111/j.1749-6632.2003.tb03243.x, 12799293.
147. Strauer BE, et al. [Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction]. Deutsche medizinische Wochenschrift 2001, 126(34-35):932-938.
148. Assmus B, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002, 106(24):3009-3017. 10.1161/01.CIR.0000043246.74879.CD, 12473544.
149. Yousef M, et al. The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. J Am Coll Cardiol 2009, 53(24):2262-2269. 10.1016/j.jacc.2009.02.051, 19520249.
150. Meyer GP, et al. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J 2009, 30(24):2978-2984. 10.1093/eurheartj/ehp374, 19773226.
151. Schachinger V, 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(8):1690-1699. 10.1016/j.jacc.2004.08.014, 15489105.
152. Wen Y, et al. Direct autologous bone marrow-derived stem cell transplantation for ischemic heart disease: a meta-analysis. Expert Opin Biol Ther 2011, 11(5):559-567. 10.1517/14712598.2011.560567, 21388335.
153. Zhang C, et al. Efficacy and safety of intracoronary autologous bone marrow-derived cell transplantation in patients with acute myocardial infarction: insights from randomized controlled trials with 12 or more months follow-up. Clin Cardiol 2010, 33(6):353-360. 10.1002/clc.20745, 20556805.
154. Hamano K, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 2001, 65(9):845-847. 10.1253/jcj.65.845, 11548889.
155. Beeres SL, et al. Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia. Am J Cardiol 2006, 97(9):1326-1331. 10.1016/j.amjcard.2005.11.068, 16635605.
156. van Ramshorst J, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 2009, 301(19):1997-2004. 10.1001/jama.2009.685, 19454638.
157. Ziegler MA, et al. Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion. Microcirculation 2010, 17(1):3-20. 10.1111/j.1549-8719.2010.00008.x, 2909670, 20141596.
158. Tateishi-Yuyama E, 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(9331):427-435. 10.1016/S0140-6736(02)09670-8, 12241713.
159. Nizankowski R, et al. The treatment of advanced chronic lower limb ischaemia with marrow stem cell autotransplantation. Kardiol Pol 2005, 63(4):351-360. discussion 361.
160. Hernandez P, 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(2):e52-e56. 10.1016/j.atherosclerosis.2006.08.025, 16982058.
161. Amann B, 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(3):371-380. 10.3727/096368909788534942, 19500466.
162. Couto BG, et al. Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study. Liver international: official journal of the International Association for the Study of the Liver 2011, 31(3):391-400.
163. Suarez-Monteagudo C, et al. Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study. Restorative neurology and neuroscience 2009, 27(3):151-161.
164. Taguchi A, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 2004, 114(3):330-338. 484977, 15286799.
165. Elhanbly S, et al. Erectile dysfunction in smokers: a penile dynamic and vascular study. J Androl 2004, 25(6):991-995.
166. You D, et al. Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy. Circulation 2006, 114(4):328-338. 10.1161/CIRCULATIONAHA.105.589937, 16847153.