Urine-Derived Stem Cells Versus Their Lysate in Ameliorating Erectile Dysfunction in a Rat Model of Type 2 Diabetes

Abstract

Background: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED.Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 μl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively.Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week.Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.

Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study

“…Hyperglycemia and oxidative stress in diabetes lead to vascular damage and reduce the blood supply of the corpus cavernous. Concurrently, hyperglycemia and advanced glycation end products promote oxidative stress and the generation of superoxide free radicals, activating multiple pathways and ultimately impelling endothelial cell injury and apoptosis [ 30 , 40 , 43 ]. These factors lead to a reduction in eNOS and VEGF synthesis, while eNOS is involved in NO/cGMP pathway and VEGF is a vital nutritional factor, which promotes angiogenesis and endothelial proliferation, increasing penis blood inflow [ 40 ].…”

“…Animal experiments, listed in Table 9 , identify the efficacy of stem cells and explore the mechanisms. ADSCs and MSCs are the most common types, in addition to USCs [ 43 ], UVECs, and AFSCs [ 47 ]. Almost all testified various stem cells could improve the ICP/MAP ratio in rats by diversified mechanisms.…”

“…Almost all testified various stem cells could improve the ICP/MAP ratio in rats by diversified mechanisms. But Galhom RA et al [ 43 ] verified the efficacy through the apomorphine. Recently, the efficacy of stem cells is considered to be exerted through secretion rather than differentiation.…”

“…Zhu GQ et al [ 40 ] demonstrated Li-ESWT upturned SDF-1 and PECAM expression to recruit MSCs, elevating VEGF, enhancing its effect. USC-L and hUSC-EVs showed the same good curative effect and raised endothelium content as stem cells [ 43 , 50 ]. Moreover, Feng H et al [ 51 ] found that HUCMSCs can inhibit ferroptosis to protect cavernous tissue and raise the level of eNOS and nNOS to recover EF of rats.…”

Power of pee: Urine‐derived stem cells in urological disorders

“…USCs have widely been studied for the treatment of various patterns of ED, including ED rat models induced by diabetes, neural injury, cardiovascular disease, and neurovascular injury [ 17,79,86,87 ] . In rodent studies, USC exosomes, extracellular vesicles, or lysate have been shown to promote the growth of new blood vessels and nerve cells in the penis, leading to improved erectile function [ 58,59,79,88 ] .…”