Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 292, Issue 3, 2007, Pages

  Bivalacqua, Trinity J ^a   Deng, Weiwen ^b   Kendirci, Muammer ^b   Usta, Mustafa F ^b   Robinson, Christine ^b   Taylor, Bradley K ^b   Murthy, Subramanyam N ^b   Champion, Hunter C ^a   Hellstrom, Wayne J G ^b   Kadowitz, Philip J ^b  

^a JOHNS HOPKINS HOSPITAL   (United States)

^b TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

cGMP; Endothelium; Gene therapy; Neuronal nitric oxide synthase; Phosphodiesterase type 5

Indexed keywords

CYCLIC GMP; ENDOTHELIAL NITRIC OXIDE SYNTHASE;

AGING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL ISOLATION; CELL SURVIVAL; CONTROLLED STUDY; ERECTILE DYSFUNCTION; EX VIVO STUDY; HISTOLOGY; MALE; MESENCHYMAL STEM CELL; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; PENIS ERECTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RAT; SIGNAL TRANSDUCTION;

AGING; ANIMALS; IMPOTENCE; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STEM CELLS; NITRIC OXIDE SYNTHASE TYPE III; RATS; RATS, INBRED BN;

EID: 33847711835     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00685.2006     Document Type: Article

References (49)

1. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 174: 386-393, 2005.
2. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19: 180-192, 2001.
3. Bivalacqua TJ, Champion HC, Mehta YS, Abdel-Mageed AB, Sikka SC, Ignarro LJ, Kadowitz PJ, Hellstrom WJ. Adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis improves age-related erectile dysfunction in the rat. Int J Impot Res 12, Suppl 3: S8-S17, 2000.
4. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, Hellstrom WJ. Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl 24, Suppl 6: S17-S37, 2003.
5. ·-- and improves erectile function in aged rats. Am J Physiol Heart Circ Physiol 284: H1408-H1421, 2003.
6. Bivalacqua TJ, Usta MF, Champion HC, Adams D, Namara DB, Abdel-Mageed AB, Kadowitz PJ, Hellstrom WJ. Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats. J Urol 169: 1911-1917, 2003.
7. Bivalacqua TJ, Usta MF, Champion HC, Leungwattanakij S, Dabisch PA, McNamara DB, Kadowitz PJ, Hellstrom WJ. Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 16: 21-29, 2004.
8. Bivalacqua TJ, Deng W, Champion HC, Hellstrom WJ, Kadowitz PJ. Gene therapy techniques for the delivery of endothelial nitric oxide synthase to the corpora cavernosa for erectile dysfunction. In: Nitric Oxide Protocols, edited by Hassid A. Totowa, NJ: Humana, 2004, p. 173-186.
9. Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, Lewis RL, Mills TM, Hellstrom WJ, Kadowitz PJ. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci USA 101: 9121-9126, 2004.
10. Bivalacqua TJ, Usta MF, Kendirci M, Pradhan L, Alvarez X, Champion HC, Kadowitz PJ, Hellstrom WJ. Superoxide anion production in the rat penis impairs erectile function in diabetes: influence of in vivo extracellular superoxide dismutase gene therapy. J Sex Med 2: 187-197, 2005.
11. Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin SC, Lue TF. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 94: 904-909, 2004.
12. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7: 14, 2006.
13. Brenner M. Gene transfer by adenovectors. Blood 94: 3965-3967, 1999.
14. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: a physiologic mediator of penile erection. Science 257: 401-403, 1992.
15. Cartledge JJ, Eardley I, Morrison JF. Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes. BJU Int 87: 394-401, 2001.
16. Champion HC, Bivalacqua TJ, Hyman AL, Ignarro LJ, Hellstrom WJ, Kadowitz PJ. Gene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat. Proc Natl Acad Sci USA 96: 11648-11652, 1999.
17. Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181: 67-73, 1999.
18. Deng W, Bivalacqua TJ, Chattergoon NN, Hyman AL, Jeter JR Jr, Kadowitz PJ. Adenoviral gene transfer of eNOS: high-level expression in ex vivo expanded marrow stromal cells. Am J Physiol Cell Physiol 285: C1322-C1329, 2003.
19. Deng W, Bivalacqua TJ, Chattergoon NN, Jeter JR Jr, Kadowitz PJ. Engineering ex vivo-expanded marrow stromal cells to secrete calcitonin gene-related peptide using adenoviral vector. Stem Cells 22: 1279-1291, 2004.
20. Deng W, Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ. Gene and stem cell therapy for erectile dysfunction. Int J Impot Res 17, Suppl 1: S57-S63, 2005.
21. Deng W, St Hilaire RC, Chattergoon NN, Jeter JR Jr, Kadowitz PJ. Inhibition of vascular smooth muscle cell proliferation in vitro by genetically engineered marrow stromal cells secreting calcitonin gene-related peptide. Life Sci 78: 1830-1838, 2006.
22. D'Souza FM, Sparks RL, Chen H, Kadowitz PJ, Jeter JR Jr. Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation. Am J Physiol Cell Physiol 284: C191-C199, 2003.
23. El-Sakka AI, Lin CS, Chui RM, Dahiya R, Lue TF. Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model. Int J Impot Res 11: 123-132, 1999.
24. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151: 54-61, 1994.
25. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528-1530, 1998.
26. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17: 331-340, 1974.
27. Garban H, Vernet D, Freedman A, Rajfer J, Gonzalez-Cadavid N. Effect of aging on nitric oxide-mediated penile erection in rats. Am J Physiol Heart Circ Physiol 268: H467-H475, 1995.
28. Gholami SS, Rogers R, Chang J, Ho HC, Grazziottin T, Lin CS, Lue TF. The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J Urol 169: 1577-1581, 2003.
29. Giuliano F, Rampin O. Neural control of erection. Physiol Behav 83: 189-201, 2004.
30. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, Snyder SH, Burnett AL. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci USA 99: 4061-4066, 2002.
31. Jones RW, Rees RW, Minhas S, Ralph D, Persad RA, Jeremy JY. Oxygen free radicals and the penis. Expert Opin Pharmacother 3: 889-897, 2002.
32. Kassem M. Mesenchymal stem cells: biological characteristics and potential clinical applications. Cloning Stem Cells 6: 369-374, 2004.
33. Kim Y, de Miguel F, Usiene I, Kwon D, Yoshimura N, Huard J, Chancellor M. Injection of skeletal muscle-derived cells into the penis improves erectile function. Int J Impot Res 18: 329-334, 2005.
34. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109: 1543-1549, 2004.
35. Lue TF. Erectile dysfunction. N Engl J Med 342: 1802-1813, 2000.
36. Magee TR, Ferrini M, Garban HJ, Vernet D, Mitani K, Rajfer J, Gonzalez-Cadavid NF. Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase. Biol Reprod 67: 1033-1041, 2002.
37. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9: 1195-1201, 2003.
38. Musicki B, Palese MA, Crone JK, Burnett AL. Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection. Biol Reprod 70: 282-289, 2004.
39. Musicki B, Kramer MF, Becker RE, Burnett AL. Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med 2: 347-355, 2005.
40. Musicki B, Burnett AL. eNOS function and dysfunction in the penis. Exp Biol Med 231: 154-165, 2006.
41. Nehra A, Steers WD, Althof SE, Andersson KE, Burnett AL, Costabile RA, Goldstein I, Kloner RA, Lue TF, Morales A, Rosen RC, Shabsigh R, Siroky MB, King L. Third International Conference on the Management of Erectile Dysfunction: Linking Pathophysiology and Therapeutic Response. J Urol 170: S3-S5, 2003.
42. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147, 1999.
43. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276: 71-74, 1997.
44. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 326: 90-94, 1992.
45. Segers VF, Van Riet I, Andries LJ, Lemmens K, Demolder MJ, De Becker AJ, Kockx MM, De Keulenaer GW. Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol 290: H1370-H1377, 2006.
46. Setter SM, Iltz JL, Fincham JE, Campbell RK, Baker DE. Phosphodiesterase 5 inhibitors for erectile dysfunction. Ann Pharmacother 39: 1286-1295, 2005.
47. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111: 150-156, 2005.
48. Squadrito GL, Pryor WA. Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med 25: 392-403, 1998.
49. Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, Yang YZ, Pan C, Ge J, Phillips MI. Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117: 3-10, 2004.