Intracavernous Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Restores Erectile Function of Streptozocin-Induced Diabetic Rats

被引:90
作者
Qiu, Xuefeng [1 ]
Lin, Haocheng [1 ]
Wang, Yajing [2 ]
Yu, Wen [1 ]
Chen, Yun [1 ]
Wang, Run [3 ,4 ]
Dai, Yutian [1 ]
机构
[1] Nanjing Univ, Affiliated Drum Tower Hosp, Sch Med, Dept Urol, Nanjing 210008, Peoples R China
[2] Nanjing Univ, Sch Med, Immunol & Reprod Biol Lab, Nanjing 210008, Peoples R China
[3] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA
[4] Univ Texas Houston, Sch Med, Dept Urol, Houston, TX 77030 USA
基金
中国国家自然科学基金;
关键词
Diabetes Mellitus; Mesenchymal Stem Cells; Erectile Dysfunction; Endothelium; Smooth Muscle; Rat Model; NITRIC-OXIDE SYNTHASE; GENE-TRANSFER; DYSFUNCTION; MODEL; TISSUE; DIFFERENTIATION; INHIBITORS; PHENOTYPE; MELLITUS; DENSITY;
D O I
10.1111/j.1743-6109.2010.02118.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Introduction. Erectile dysfunction (ED) is a frequent complication of diabetes mellitus. The efficacy of common ED therapies is low for diabetes-associated ED. Aim. To explore the effects of transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) on improving erectile function of streptozocin (STZ)-induced diabetic rats. Methods. Male Sprague Dawley rats were injected either with STZ to induce diabetes or with citrate buffer as controls. Rat BM-MSCs were harvested and labeled with CM-DiI (Chloromethylbenzamido derivatives of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), and then transplanted into corporal cavernosum of STZ-induced diabetic rats. Four weeks after transplantation, all rats were analyzed for erectile function and penile histology. Main Outcome Measures. Erectile function was evaluated by the ratio between intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of cavernous nerve. Fate of transplanted BM-MSCs was identified using immunofluorescence staining. Smooth muscle and endothelium in corpora cavernosum were assessed using immunohistochemistry. Results. After BM-MSCs transplantation, the ICP/MAP ratio was increased significantly compared with diabetic controls. Content of smooth muscle and endothelium in corporal cavernosa of BM-MSCs transplanted rats was significantly increased compared to diabetic controls. Immunofluorescence analysis demonstrated that CM-DiI-labeled BM-MSCs could stay in corporal cavernosa for at least 4 weeks and some of them expressed von Willebrand Factor, CD31, calponin, or alpha-smooth muscle actin, cells markers for endothelial cells or smooth muscle cells, respectively. Conclusion. Intracavernous transplantation of BM-MSCs had beneficial effects on erectile function of diabetic rats and increased the content of endothelium and smooth muscle in corporal cavernosum. Qiu X, Lin H, Wang Y, Yu W, Chen Y, Wang R, and Dai Y. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 2011;8:427-436.
引用
收藏
页码:427 / 436
页数:10
相关论文
共 35 条
[1]   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].
Albersen, Maarten ;
Fandel, Thomas M. ;
Lin, Guiting ;
Wang, Guifang ;
Banie, Lia ;
Lin, Ching-Shwun ;
Lue, Tom F. .
JOURNAL OF SEXUAL MEDICINE, 2010, 7 (10) :3331-3340
[2]   Superoxide anion production in the rat penis impairs erectile function in diabetes: Influence of in vivo extracellular superoxide dismutase gene therapy [J].
Bivalacqua, TJ ;
Usta, MF ;
Kendirci, M ;
Pradhan, L ;
Alvarez, X ;
Champion, HC ;
Kadowitz, PJ ;
Hellstrom, WJG .
JOURNAL OF SEXUAL MEDICINE, 2005, 2 (02) :187-197
[3]   Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats [J].
Bivalacqua, TJ ;
Usta, MF ;
Champion, HC ;
Adams, D ;
McNamara, DB ;
Abdel-Mageed, AB ;
Kadowitz, PJ ;
Hellstrom, WJG .
JOURNAL OF UROLOGY, 2003, 169 (05) :1911-1917
[4]   Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction [J].
Bivalacqua, Trinity J. ;
Deng, Weiwen ;
Kendirci, Muammer ;
Usta, Mustafa F. ;
Robinson, Christine ;
Taylor, Bradley K. ;
Murthy, Subramanyam N. ;
Champion, Hunter C. ;
Hellstrom, Wayne J. G. ;
Kadowitz, Philip J. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 292 (03) :H1278-H1290
[5]   Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat [J].
Burchardt, T ;
Burchardt, M ;
Karden, J ;
Buttyan, R ;
Shabsigh, A ;
de la Taille, A ;
Ng, PY ;
Anastasiadis, AG ;
Shabsigh, R .
JOURNAL OF UROLOGY, 2000, 164 (05) :1807-1811
[6]   Gene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat [J].
Champion, HC ;
Bivalacqua, TJ ;
Hyman, AL ;
Ignarro, LJ ;
Hellstrom, WJG ;
Kadowitz, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (20) :11648-11652
[7]   Endothelial rehabilitation: The impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats [J].
De Young, Ling X. ;
Domes, Trustin ;
Lim, KokBin ;
Carson, Jeffery ;
Brock, Gerald B. .
EUROPEAN UROLOGY, 2008, 54 (01) :213-220
[8]   Apoptosis and Effects of Intracavernous Bone Marrow Cell Injection in a Rat Model of Postprostatectomy Erectile Dysfunction [J].
Fall, Papa Ahmed ;
Izikki, Mohamed ;
Tu, Li ;
Swieb, Salem ;
Giuliano, Francois ;
Bernabe, Jacques ;
Souktani, Rachid ;
Abbou, Claude ;
Adnot, Serge ;
Eddahibi, Saadia ;
Yiou, Rene .
EUROPEAN UROLOGY, 2009, 56 (04) :716-725
[9]   IMPOTENCE AND ITS MEDICAL AND PSYCHOSOCIAL CORRELATES - RESULTS OF THE MASSACHUSETTS MALE AGING STUDY [J].
FELDMAN, HA ;
GOLDSTEIN, I ;
HATZICHRISTOU, DG ;
KRANE, RJ ;
MCKINLAY, JB .
JOURNAL OF UROLOGY, 1994, 151 (01) :54-61
[10]   STROMAL CELLS FROM HUMAN LONG-TERM MARROW CULTURES ARE MESENCHYMAL CELLS THAT DIFFERENTIATE FOLLOWING A VASCULAR SMOOTH-MUSCLE DIFFERENTIATION PATHWAY [J].
GALMICHE, MC ;
KOTELIANSKY, VE ;
BRIERE, J ;
HERVE, P ;
CHARBORD, P .
BLOOD, 1993, 82 (01) :66-76