Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats

Zhu, Li; Huang, Xinting; Yao, Wen; Chen, H.; Chen, Y.; Dai, Yutian

doi:10.1111/and.12871

Cited by 95 publications

(71 citation statements)

References 48 publications

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“…They found that not only ADSCs but also ADSCs‐derived EXOs could partly restore erectile function of diabetic rats by suppressing the apoptosis of corpus cavernosum smooth muscle and endothelial cells (Chen et al ., ). Zhu et al ., () also demonstrated that ADSCs‐derived EXOs show proangiogenic properties via inducing the proliferation of endothelial cells in vitro and therapeutical effect on diabetic ED through decreasing fibrosis. It is further revealed that cell‐free therapy has great potential in the treatment of ED and more attention should be paid on the relationship between ADSCs‐derived EXOs and ED.…”

Section: Discussionmentioning

confidence: 85%

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Yang

Zhang

Zang³

et al. 2018

Andrology

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Adipose-derived stem cells (ADSCs) have recently been considered as a promising therapy for erectile dysfunction (ED). However, the mechanism of ADSC-based therapy is unclear. Insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed in vitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment with labeled ADSCs or PBS. Eight additional 5-month-old rats were used as a young rat group. At 2 weeks post-transplantation, all rats were analyzed for erectile function, cavernous IGF-1, bFGF and VEGF levels, and penile histology. Conditioned medium and co-culture systems were used in cell experiments to detect how growth factors act on corpus cavernosum smooth muscle cells (CCSMCs) under oxidative stress conditions via crystal violet staining and immunofluorescence staining. We found that ADSCs secreted significantly higher IGF-1, bFGF, and VEGF levels in culture medium compared with basal medium. Compared with young rats, untreated aged rats had significantly lower Max ICP/MAP and ADSC treatment significantly increased the ratio. Immunofluorescence staining demonstrated a small number of labeled ADSCs in the corpus cavernosum. The untreated aged rats showed significantly decreased cavernous IGF-1, bFGF, and VEGF levels and significantly decreased contents of cavernous smooth muscle and endothelium compared with young rats. ADSC treatment partially normalized these alterations. In cell experiments, the groups receiving growth factor neutralizing antibody separately or combined had significantly decreased numbers of CCSMCs compared with control groups. These results indicated that ADSC treatment may improve aging-related ED partially through the secretion of IGF-1, bFGF, and VEGF.

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Section: Discussionmentioning

confidence: 85%

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Yang

Zhang

Zang³

et al. 2018

Andrology

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“…Recently, injection of exosomes for treating ED in a type 2 diabetic ED rat model and in STZ‐diabetic rat model has been reported, respectively. Chen et al ., () found that ADSC‐derived exosomes were capable of rescuing corpus cavernosum endothelial and smooth muscle cells by inhibiting apoptosis and thus promoting the recovery of erectile function in type 2 diabetic rats; Zhu et al ., () demonstrated ADSC‐derived exosomes had the ability to promote angiogenesis and proliferating endothelial cells in vitro and restored erectile function in vivo, which was preliminarily explained by proangiogenic microRNAs (miR‐126, miR‐130a and miR‐132) detected in the ADSC‐derived exosomes.…”

Section: Discussionmentioning

confidence: 91%

Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury

Lei

et al. 2018

Andrology

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Postradical prostatectomy erectile dysfunction (pRP-ED) is a major health issue. There has been a shortage of an effective treatment method until now. In this study, a total of 48 adult male Sprague-Dawley (SD) rats were randomly equally divided into four groups, including group 1-sham surgery with cavernous nerve exposure plus vehicle, group 2-bilateral cavernous nerve injury (BCNI) plus vehicle, group 3-BCNI plus adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSC-Exo), and group 4-BCNI plus bone marrow-derived mesenchymal stem cell (BMSCs)-derived exosomes (BMSC-Exo). Twenty-one days following surgery, erectile function was measured before tissue harvest. Histologic and Western blot analyses were then performed. Exosomes were capable of internalization into human umbilical vein endothelial cells (HUVEC) in vitro and could be detected in the corpus cavernosum in vivo. The nNOS expression in the penile dorsal nerves (DN) and major pelvic ganglion (MPG), protein level of neurofilament in the DN, endothelial markers vWF, alpha smooth muscle actin (α-SMA), the ratio of smooth muscle to collagen content were obviously lower in BCNI group compared with the sham group, while ADSC-Exo and BMSC-Exo groups resulted in significant restoration of the above histopathological changes. Moreover, BCNI treated with ADSC-Exo or BMSC-Exo had significantly higher mean intracavernous pressure/mean arterial pressure ratio compared with BCNI group. The results demonstrated that both ADSC-Exo and BMSC-Exo treatment could significantly alleviate pathological changes and improve the erectile function in BCNI-related rats. Exosomes derived from ADSCs and BMSCs may be a potential agent for pRP-ED treatment.

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“…One study showed that exosomes from AT‐MSCs enhanced endothelial cell proliferation and decreased fibrosis of corpus cavernosum in a model of STZ‐induced T1D . Part of these effects could be mediated by the transfer of proangiogenic ( miR‐126 , miR‐130a , and miR‐132 ) and antifibrotic ( let‐7b and let‐7c ) miRNAs . Another study demonstrated similarly beneficial effects in a model of T2D by combined HFD and STZ injection .…”

Section: Exosomes As Therapy For Diabetesmentioning

confidence: 96%

“…Hence, exosomes derived from adipose stem cells were shown in several studies to improve erectile function of diabetic rats. One study showed that exosomes from AT‐MSCs enhanced endothelial cell proliferation and decreased fibrosis of corpus cavernosum in a model of STZ‐induced T1D . Part of these effects could be mediated by the transfer of proangiogenic ( miR‐126 , miR‐130a , and miR‐132 ) and antifibrotic ( let‐7b and let‐7c ) miRNAs .…”

Section: Exosomes As Therapy For Diabetesmentioning

confidence: 99%

Exosomes and diabetes

Castaño

Novials

Párrizas

2019

Diabetes Metabolism Res

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Summary Diabetes is a group of metabolic diseases characterized by elevated blood glucose levels that drive the development of life‐threatening complications. Diabetes results from a situation of insufficient insulin action, either by deficient production of the hormone by the pancreas, or by the development of insulin resistance in peripheral tissues such as liver, muscle, or the adipose depots. Communication between organs is thus central to the maintenance of glucose homoeostasis. Recently, several studies are evidencing that small vesicles called exosomes released by, amongst other, the adipose tissue can regulate gene expression in other tissues, hence modulating interorgan crosstalk. Therefore, exosomes participate in the development of diabetes and its associated complications. Their study holds the potential of providing us with novel biomarkers for the early diagnosis and stratification of patients at risk of developing diabetes, hence allowing the timely implementation of more personalized therapies. On the other hand, the molecular dissection of the pathways initiated by exosomes under situations of metabolic stress could help to gain a deeper knowledge of the pathophysiology of diabetes and its associated metabolic diseases.

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Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats

Cited by 95 publications

References 48 publications

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury

Exosomes and diabetes

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