Tags: erectile dysfunction stem cells. Leave a Reply Cancel reply Your email address will not be published. You may have missed. Diabetes 7 min read. Diabetes Trends. Adnot S. Eddahibi S. Yiou R. Apoptosis and effects of intracavernous bone marrow cell injection in a rat model of postprostatectomy erectile dysfunction. Eur Urol. Song Y. Mehta N. Sheh B. Saljooque F. Rajasekaran M. Transdifferentiation of rat fetal brain stem cells into penile smooth muscle cells.
Garcia MM. Shindel AW. Banie L. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. Harraz AM. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. Abdel Aziz MT. El-Haggar S. Mostafa T. Atta H. Fouad H. Mahfouz S. Rashed L. Sabry D. Senbel A. Ali GA. Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats.
Bahk JY. Jung JH. Han H. Min SK. Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. Wang G. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. Trost L. Bakondi B. Whitney MJ. Spees JL. Lin H. Wang Y. Chen Y. Wang R. Dai Y. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats.
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Tissue Eng. Yang H. Several studies have suggested the use of stem cells for the treatment of ED and showed that this type of treatment is promising in terms of damaged tissue repair as well as of clinical efficacy; however, there are several gaps in the knowledge and evidence is lacking.
In order to highlight a few of them in this review, we performed a research of the literature focusing on currently available clinical studies regarding the clinical efficacy of stem cell administration for the treatment of ED. We reviewed the methods of administration, the cell types used in the performed clinical trials and the safety and efficiency of such procedures.
We conclude that there are rapidly expanding and promising results from the reported clinical studies indicating that stem cells could indeed be a potential treatment for patients with ED although more studies are necessary. Erectile dysfunction ED is a common condition that refers to the inability of a male individual to attain and maintain sufficient penile erection for sexual intercourse [ 1 ].
It is classified as organic, psychogenic or neurogenic [ 2 ]. Over the past years, ED has raised increased concern and has been recognized as a public health problem [ 3 ].
The majority of these disorders are associated with endothelial dysfunction, which is linked to the severity of ED as the corpora cavernosa vascular homeostasis is mainly regulated by the vascular endothelium [ 7 ]. Other factors that play a significant role in the development of ED are the damage of the nerves that are responsible for the erection, side effects due to drug medication and alterations in hormone levels such as testosterone [ 8 ].
Until recently, the treatment of ED has mainly been based on the transient enhancement of penile erection but without a permanent reversal of endothelial dysfunction or restoration of the disturbed penile tissue homeostasis. Current treatment options include phosphodiesterase type-5 inhibitors PDE5is such as vardenafil, avanafil, tadalafil and sildenafil, which are the most widely known and used medications for the treatment of ED.
In brief, penile erection requires arterial smooth muscle cells SMC relaxation to facilitate blood flow in the penile tissue i. The main metabolite inducing SMC relaxation is NO provided by the nonadrenergic noncholinergic postganglionic parasympathetic neurons and the endothelium. Of note, the last ten years of reports have expanded our knowledge by indicating that PDE5is also stimulate bone marrow endothelial progenitor cell function and inhibit the apoptosis of smooth muscle cells [ 10 , 11 , 12 , 13 , 14 ].
Unfortunately, the treatment failure levels with PDE5is are unacceptably high. Therefore, additional treatment options for the management of ED are needed and include the use of intracorporal injections, vacuum erection devices and penile prosthesis implantation. However, their application is also limited due to the high cost, intolerance to side effects, pain and unsatisfactory results [ 8 ].
Consequently, the need to develop efficient curative treatments for patients with ED turned the scientific interest toward the study of stem cell therapy [ 6 ].
In this systematic review, we aim to shed light into the gaps in knowledge and evidence regarding the potential use of stem cells for ED treatment and provide an overview of the currently available knowledge and concerns. Stem cells are undifferentiated or partially differentiated cells, which are characterized by their ability to self-renew and differentiate into more specialized cell types [ 16 ].
Generally, stem cells are classified as totipotent e. When a stem cell is divided, the daughter cells can either remain stem cells or differentiate into a specialized cell type, e.
Their ability for division, differentiation and tissue regeneration is affected by their environment, which supports the stem cells and interacts with them, affecting their transformation to dedicated cell types and promoting their self-renewal [ 19 ].
In these sites they could regenerate the damaged tissues according to the stimuli or the received signals [ 18 ]. Stem cells have been used for the treatment of many diseases since the s and have shown promising potential, thus allowing scientists to consider their use as a plausible candidate approach [ 21 , 22 ]. It is possible that diseases or pathological conditions of the urinary system would also benefit from the use of stem cells.
In recent years, stem cell therapy has been proposed for the treatment of ED as stem cells can differentiate to endothelial, neuronal or smooth muscle cells and therefore restore possible structural damage in the penile tissue.
In vitro stem cell differentiation in these cell lines has been proven while preclinical studies showed improvement in ED following stem cell therapy in several animal models [ 31 , 32 , 33 ].
However, the exact mechanism has not yet been proven and also includes the paracrine action of stem cells as another possible mechanism in ED shown in animal models [ 32 ]. Clinical studies with the use of stem cells have also been published with encouraging results [ 21 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].
Questions regarding the clinical use of stem cells include the type of stem cells, the method of preparation, the optimal number of stem cells and the method of administration. Different ways of stem cell administration have been suggested and examined. Specifically, reported preclinical works have examined the effect of intraperitoneal and intravenous injection and suggested that the latter was more efficacious in improving erectile function [ 44 , 45 , 46 ].
Periprostatic implantation has also been performed in other works and the results depicted an equal efficacy with an intracavenosal injection [ 47 , 48 ].
Although only a limited number of stem cells remained in the target tissues after injection, they created a significant effect by triggering endogenous mechanisms of regeneration and promoted the propagation and differentiation of progenitor cells, thus improving the recovery of the target tissue [ 46 , 49 , 50 , 51 ].
Regarding ED treatment, in all of the clinical studies so far stem cell delivery has been studied by direct injection in the target tissue of the penis or an intracavernosal injection. In the clinical studies published so far, the stem cells used have been BMSC, ADSC, umbilical cord stem cells and placenta-derived stem cells [ 21 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. In terms of preparations, there have been two basic techniques to prepare stem cells.
One is the isolation of the stem cells from the tissue obtained from the donor and then used directly or expanded in culture to obtain greater numbers of stem cells. SVF is a product of the adipose tissue obtained by the donor and it is created in a process that includes centrifugation of the fatty tissue harvested.
SVF is a product of the centrifugation and contains stem cells but also endothelial precursor cells, growth factors and immune modulatory cells [ 52 ]. Although by expanding the stem cells you can obtain a greater number compared with stem cells in SVF, the additional cells and factors included in the SVF seem to collaborate with the stem cells and the final clinical result might be even better although no final conclusion has been made [ 53 ]. An overview of clinical studies is presented in Table 1.
The first clinical study was published in by a Korean team. Bahk et al. Umbilical cord stem cells 1. The results revealed that the majority of their participants regained their morning erections within one month and maintained this for more than six months.
Moreover, their blood glucose levels decreased after two weeks, highlighting that human umbilical cord blood stem cell therapy provided positive outcomes in both ED and diabetes conditions. A 35 year old patient with a past medical history of smoking and hypercholesterolemia was suffering from ED and he was unresponsive to PDE5 inhibitors.
He was treated with BMSC without specifying the number of stem cells used. There was a return in spontaneous erections but he still required medication PDE5is to sustain them until orgasm. The beneficial effect was present 18 months post-treatment. Another significant study from evaluated for the first time the use of various stem cell numbers per injection.
Yiou et al. Their results revealed that a significant improvement without serious side effects was observed in the patients who received the highest dose of stem cells at six months post-treatment, which was associated with improvements in their peak systolic velocity measured by penile triplex. The broad use of these cells could be attributed to their easy isolation by specific devices, their abundance in the tissues, their similar properties to BMSC and their proven therapeutic efficacy [ 15 ].
The isolation of such cells demands firstly the separation of the SVF from the adipose tissue harvested, as already mentioned.
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