Mesenchymal Stem Cells Enhance Vascular Endothelial Growth Factor-A, Endothelial Nitric Oxide Synthetase, and HSP70 Expression in Improving Erectile Dysfunction in Streptozotocin-induced Diabetic Rats (original) (raw)
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The Journal of Sexual Medicine, 2012
Introduction. Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. Aim. To examine whether and how freshly isolated stromal vascular fraction (SVF) promotes cavernous endothelial regeneration and restores erectile function in diabetic animals. Methods. Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice. At 8 weeks after the induction of diabetes, the animals were divided into six groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 ¥ 10 4 cells, 1 ¥ 10 5 cells, or 2 ¥ 10 5 cells/20 mL, respectively). Main Outcome Measures. Two weeks later, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to CD31, CD34, phosphohistone H3, phospho-endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor-A (VEGF-A). We also performed Western blot for phospho-eNOS and eNOS, and determined cyclic guanosine monophosphate (cGMP) concentration in the corpus cavernosum tissue. Results. Significant improvement in erectile function was noted in diabetic mice treated with SVF at concentrations of 1 ¥ 10 5 and 2 ¥ 10 5 cells, which reached up to 82% of the control values. Local delivery of SVF significantly increased cavernous endothelial cell proliferation, eNOS phosphorylation, and cGMP expression compared with that in the untreated group and the PBS-treated diabetic group. Intracavernous injection of SVF increased cavernous VEGF-A expression and induced recruitment of CD34(+)CD31(-) progenitor cells. Some SVF underwent differentiation into cavernous endothelial cells. SVF-induced promotion of cavernous angiogenesis and erectile function was abolished in the presence of VEGF-Trap, a soluble VEGF-A neutralizing antibody. Conclusion. The results support the concept of cavernous endothelial regeneration by use of SVF as a curative therapy for diabetic ED.
American Journal of Physiology-heart and Circulatory Physiology, 2006
Mesenchymal stem cells (MSCs) can be used in adult stem cell-based gene therapy for vascular diseases. To test the hypothesis that MSC alone or eNOS modified MSCs can be used for treatment of erectile dysfunction (ED), syngeneic rat MSCs (rMSCs) were isolated, ex vivo expanded, transduced with adenovirus containing endothelial nitric oxide synthase (eNOS), and injected into the penis of aged rats. Histological analysis demonstrated that rMSCs survived for at least 21 days in corporal tissue after intracavernous injection and an inflammatory response was not induced. Intracavernous administration of eNOS-modified rMSCs improved the erectile response in aged rats at 7 and 21 days after injection. The increase in erectile function was associated with increased eNOS protein, NOS activity and cGMP levels. rMSCs alone increased erectile function of aged rats at day 21, but not at day 7, with the transplanted cells exhibiting positive immunostaining for several endothelial and smooth muscle cell markers.
2019
Background：Diabetes mellitus (DM) is an important risk factor for erectile dysfunction (ED). Adipose-derived stem cells (ADSCs) and low-intensity extracorporeal shockwave therapy (LI-ESWT) are two emerging therapies for ED. The efficacy of ADSCs combined LI-ESWT in the treatment of diabetes induced erectile dysfunction (DMED) was not completely elucidated. This study aim to investigate combined therapeutic efficacy of ADSCs and LI-ESWT in rat model of DMEDand whether they have interaction.Methods：Rats were randomly divided into 5 groups: control, erectile dysfunction group (ED), ADSCs treatment group(ADSCs), LI-ESWT treatment group (LI-ESWT) and ADSCs combined with LI-ESWT treatment (ADSCs+LI-ESWT). After 4 weeks, erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP), after that performed immunohistochemistry (IH).Results：Finally, a total of 98 rats completed the experiment. The ICP/MAP of five groups under the voltage stimulation of 10V...
Urologia Internationalis, 2021
Background and Objectives: Stem cell therapy is a novel treatment with regenerative ability that can treat erectile dysfunction (ED). This phase 1/2 clinical trial (NCT02945449) using 2 consecutive intracavernous (IC) injections of allogeneic Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) was studied for the first time in the treatment of diabetic patients with ED. The primary outcome was to assess the safety and tolerability, and the secondary outcome was to assess the efficacy of 2 consecutive IC injections of allogeneic WJ-MSCs in diabetic ED. Patients and Methods: Twenty-two diabetic patients with refractory ED were included. Two consecutive IC injections of allogeneic WJ-MSCs were performed. Tolerability was assessed immediately, and at 24 h, safety was evaluated for 12 months. Efficacy was assessed using International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), and Color Duplex Doppler Ultrasound for 12 months. Results: The procedure was wel...
The journal of sexual medicine, 2016
Muscle-derived stem cells (MDSCs) and other SCs implanted into the penile corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic rat models by replenishing lost corporal smooth muscle cells (SMCs) and decreasing fibrosis. However, there are no conclusive data from models of type 2 diabetes (T2D) and obesity. To determine whether MDSCs from obese Zucker (OZ) rats with T2D at an early stage of diabetes (early diabetic SCs isolated and cultured in low-glucose medium [ED-SCs]) counteract corporal veno-occlusive dysfunction and corporal SMC loss or lipo-fibrosis when implanted in OZ rats at a late stage of diabetes and whether MDSCs from these OZ rats with late diabetes (late diabetic SCs isolated and cultured in high-glucose medium [LD-SC]) differ from ED-SCs in gene transcriptional phenotype and repair capacity. ED-SCs and LD-SCs were compared by DNA microarray assays, and ED-SCs were incubated in vitro under high-glucose conditions (ED-HG-SC). These three MDSC types were...
Stem cell therapy and diabetic erectile dysfunction: A critical review
World Journal of Stem Cells, 2021
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the
Andrologia, 2010
Stem cell-based therapy targeted at the penile tissue has been lately considered in preclinical studies. This work aimed to assess the effect of intracavernous administration of mesenchymal stem cells (MSCs) in aged rats (n = 100). They were subjected to single intracavernous injection (ICI) of 1.0 million MSCs, followed up for 3, 4 weeks, 3 and 4 months (each group 25 rats) and compared with both adult and aged controls (n = 50). In dissected cavernous tissues, cGMP and histopathology were assessed in addition to intracavernous pressure (ICP) measurement in some anaesthetised rats. The results showed that cavernous tissue cGMP was significantly increased in MSCs transplanted rats in all investigated groups compared with the controls. The mean cavernous cGMP levels after 3 and 4 months of MSCs transplantation were significantly increased compared with those after 3 or 4 weeks. Cavernous tissue ICP measurement showed significant increase in MSCs transplanted groups compared with the controls, more in the long-term follow up than in the shorter one. Histopathological examination detected markedly dilated sinusoidal vascular spaces in the long-term follow-up study. It is concluded that stem cell-based therapy is feasible for age-associated erectile dysfunction and could improve erectile signaling.
International Journal of Molecular Sciences, 2022
Erectile dysfunction is a common complication associated with type 2 diabetes mellitus (T2DM) and after prostatectomy in relation to cancer. The regenerative effect of cultured adipose-derived stem cells (ASCs) for ED therapy has been documented in multiple preclinical trials as well as in recent Pase 1 trials in humans. However, some studies indicate that diabetes negatively affects the mesenchymal stem cell pool, implying that ASCs from T2DM patients could have impaired regenerative capacity. Here, we directly compared ASCs from age-matched diabetic Goto–Kakizaki (ASCGK) and non-diabetic wild type rats (ASCWT) with regard to their phenotypes, proteomes and ability to rescue ED in normal rats. Despite ASCGK exhibiting a slightly lower proliferation rate, ASCGK and ASCWT proteomes were more or less identical, and after injections to corpus cavernosum they were equally efficient in restoring erectile function in a rat ED model entailing bilateral nerve crush injury. Moreover, molecul...