Volume 46, Issue 5 pp. 479-486

Original Article

Transplantation KCNMA1 modified bone marrow-mesenchymal stem cell therapy for diabetes mellitus-induced erectile dysfunction

Y. He,

Y. He

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Department of Urology, Suining Central Hospital, Sichuan, China

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W. He,

W. He

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

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G. Qin,

G. Qin

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

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J. Luo,

J. Luo

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

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M. Xiao,

Corresponding Author

M. Xiao

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Correspondence

Prof. Mingzhao Xiao, Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.

Tel.: +86 23 89012505;

Fax: +86 23 68811487;

E-mail: [email protected]

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Y. He,

Y. He

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Department of Urology, Suining Central Hospital, Sichuan, China

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W. He,

W. He

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

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G. Qin,

G. Qin

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Search for more papers by this author

J. Luo,

J. Luo

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

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M. Xiao,

Corresponding Author

M. Xiao

Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Correspondence

Prof. Mingzhao Xiao, Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.

Tel.: +86 23 89012505;

Fax: +86 23 68811487;

E-mail: [email protected]

Search for more papers by this author

First published: 06 May 2013

https://doi.org/10.1111/and.12104

Citations: 30

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Summary

This study assessed the effect of KCNMA1 transfected bone marrow-mesenchymal stem cells (BM-MSCs) on the improvement of erectile function in diabetic rats. Sixty male Sprague–Dawley rats were injected with streptozotocin (STZ) and screened with apomorphine (APO) to establish diabetes mellitus-induced erectile dysfunction (DMED). DMED rats were randomly divided into four groups: rats in each group underwent intracavernous injection with either phosphate buffer solution (DMED+PBS), nontransfected MSCs (DMED+MSCs), empty vector transfected MSCs (DMED+null-MSCs) or KCNMA1 transfected MSCs (DMED+KCNMA1-MSCs). Before injection, high levels of KCNMA1 expression were confirmed in KCNMA1-MSCs using RT-PCR and Western blotting. The lentivirus transfected MSCs maintained their potential for multidirectional differentiation. Four weeks after injection, erectile function was ascertained by measuring intracavernous pressure (ICP). Penile tissues were collected for immunohistochemical analysis. The expression of KCNMA1 in the corpus cavernosum was increased, and the DMED+KCNMA1-MSCs group displayed a significant improvement of erectile function. We concluded that KCNMA1 was able to enhance the positive effect of MSCs in the treatment of diabetes-associated erectile dysfunction.

References

Brink PR, Valiunas V, Wang HZ, Zhao W, Davies K, Christ GJ (2006) Experimental diabetes alters connexin43 derived gap junction permeability in short-term cultures of rat corporeal vascular smooth muscle cells. J Urol 175: 381–386.
10.1016/S0022-5347(05)00007-8
CAS PubMed Web of Science® Google Scholar
Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L (1993) mSlo, a complex mouse gene encoding”maxi”calcium-activated potassium channels. Science 261: 221–224.
10.1126/science.7687074
CAS PubMed Web of Science® Google Scholar
Christ GJ, Andersson KE, Williams K, Zhao W, D'Agostino R Jr, Kaplan J, Aboushwareb T, Yoo J, Calenda G, Davies KP, Sellers RS, Melman A (2009) Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys. Eur Urol 56: 1055–1066.
10.1016/j.eururo.2008.12.016
CAS PubMed Web of Science® Google Scholar
Fridenstein A, Piatetskii S, Petrakova KV (1969) Osteogenesis in transplants of bone marrow cells. Arkh Anat GistoI Embriol 56: 3–11.
Google Scholar
Ghatta S, Nimmagadda D, Xu X, O'Rourke ST (2006) Large conductance, calcium-activated potassium channels: structural and functional implications. Pharmacol Ther 110: 103–116.
10.1016/j.pharmthera.2005.10.007
CAS PubMed Web of Science® Google Scholar
Gratzke C, Angulo J, Chitaley K, Dai YT, Kim NN, Paick JS, Simonsen U, Uckert S, Wespes E, Andersson KE, Lue TF, Stief CG (2010) Anatomy, physiology, and pathophysiology of erectile dysfunction. J Sex Med 7: 445–475.
10.1111/j.1743-6109.2009.01624.x
CAS PubMed Web of Science® Google Scholar
Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, Vardi Y, Wespes E; European Association of Urology (2010) Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 57: 804–814.
10.1016/j.eururo.2010.02.020
PubMed Web of Science® Google Scholar
Jamnig A, Lepperdinger G (2012) From tendon to nerve: an MSC for all seasons. Can J Physiol Pharmacol 90: 295–306.
10.1139/y11-109
CAS PubMed Web of Science® Google Scholar
Koi PT, Milhoua PM, Monrose V, Melman A, DiSanto ME (2007) Expression of myosin isoforms in the smooth muscle of human corpus cavernosum. Int J Impot Res 19: 62–68.
10.1038/sj.ijir.3901503
CAS PubMed Web of Science® Google Scholar
Lin G, Qiu X, Fandel T, Banie L, Wang G, Lue TF, Lin CS (2011) Tracking intracavernously injected adipose-derived stem cells to bone marrow. Int J Impot Res 23: 268–275.
10.1038/ijir.2011.38
CAS PubMed Web of Science® Google Scholar
Nangle MR, Cotter MA, Cameron NE (2004) Effects of the peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice. Eur J Pharmacol 502: 143–148.
10.1016/j.ejphar.2004.08.033
CAS PubMed Web of Science® Google Scholar
Penson DF, Latini DM, Lubeck DP, Wallace KL, Henning JM, Lue TF (2003) Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction(EXCEED) database. Diabetes Care 26: 1093–1099.
10.2337/diacare.26.4.1093
PubMed Web of Science® Google Scholar
Qiu X, Sun C, Yu W, Lin H, Sun Z, Chen Y, Wang R, Dai Y (2012) Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction. J Androl 33: 37–44.
10.2164/jandrol.110.012666
CAS PubMed Web of Science® Google Scholar
Rendell MS, Rajfer J, Wicker PA, Smith MD (1999) Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group. JAMA 281: 421–426.
10.1001/jama.281.5.421
CAS PubMed Web of Science® Google Scholar
Salkoff L, Butler A, Ferreira G, Santi C, Wei A (2006) High-conductance potassium channels of the SLO family. Nat Rev Neurosci 7: 921–931.
10.1038/nrn1992
CAS PubMed Web of Science® Google Scholar
Setter SM, Iitz JL, Fincham JE, Campbell RK, Baker DE (2005) Phosphodiesterase 5 inhibitors for erectile dysfunction. Ann Pharmacother 39: 1286–1295.
10.1345/aph.1E487
CAS PubMed Web of Science® Google Scholar
Shabsigh R (2004) Therapy of ED: PDE-5 Inhibitors. Endocrine 23: 135–141.
10.1385/ENDO:23:2-3:135
CAS PubMed Web of Science® Google Scholar
Song YS, Lee HJ, Park IH, Kim WK, Ku JH, Kim SU (2007) Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res 19: 378–385.
10.1038/sj.ijir.3901539
CAS PubMed Web of Science® Google Scholar
Wespes E, Amar E, Hatzichristou DG, Montorsi F, Pryor J, Vardi Y (2002) European Association of Urology Guidelines on erectile dysfunction. Eur Urol 41: 1–5.
10.1016/S0302-2838(01)00008-2
PubMed Web of Science® Google Scholar
Zotova EG, Schaumburg HH, Raine CS, Cannella B, Tar M, Melman A, Arezzo JC (2008) Effects of hyperglycemia on rat cavernous nerve axons: a functional and ultrastructural study. Exp Neurol 213: 439–447.
10.1016/j.expneurol.2008.07.009
CAS PubMed Web of Science® Google Scholar

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