Scientific Related Articles

See the below studies which highlight the potential role of myostatin follistatin balance in erectile dysfunction recovery.

Related Articles

Sonic hedgehog regulation of cavernous nerve regeneration – Click Here
Highlights
•SHH protein is more effective in promoting neurite formation/CN regeneration in aged rats than in the adult.
•The first 48 h after CN injury are a critical window when growth factors are released, that impact later neurite formation.
•SHH pathway signaling machinery remains intact in aged MPG/CN and are able to respond to exogenous SHH protein.
•These studies are significant because the aged prostatectomy model will more accurately simulate ED patient response.
•Understanding how neurite formation changes with age is critical for clinical translation of SHH PA to prostatectomy patients

The Use of Bioelectrical Stimulation in the Treatment of Erectile Dysfunction – Click Here

Radial Pressure Pulse Therapy a Complementary Adjunctive Technology to MyoStim ED ErectiStim and ErectiStim Plus Biologics Therapies – Click Here

Electrical stimulation promotes the angiogenic potential of adipose-derived stem cells – Click Here

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration – Click Here

Altered Sonic Hedgehog Signaling Is Associated with Morphological Abnormalities in the Penis of the BB/WOR Diabetic Rat1 – Click Here

Predictors of Sexual Desire and Sexual Function in Sedentary Middle-Aged Adults: The Role of Lean Mass Index and S-Klotho Plasma Levels. The FIT-AGEING Study April 2020Volume 17, Issue 4, Pages 665–677 – Click Here

Myostatin protein was measured by western blots in the penile shaft of rats subjected … that were left untreated, or treated (45 days) with muscle-derived stem cells … the loss of corporal SMC occurring in certain forms of erectile dysfunction (ED). … Regulation of brown adipocyte metabolism by myostatin/ follistatin signaling.
 
smsna.org/present/getpresentation.php?tfn=89.pdf
Since erectile dysfunction is associated … Myostatin. 40 111 29 27. ActRIIb Mst receptor 85 69 97 95. Follistatin Anti-Mst … interfere with stem cells treatment.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in …

https://pdfs.semanticscholar.org/d56e/50be41ecaef42b581f96681539219242ecae.pdf
by H Li – ‎2016 – ‎Cited by 37 – ‎Related articles

Regenerative technology for future therapy of erectile dysfunction …

tau.amegroups.com/article/view/1064/1288

by JK Ryu – ‎2012 – ‎Cited by 1 – ‎Related articles

Regenerative technology for future therapy of erectile dysfunction. … smooth muscle relaxation, endothelial nitric oxide synthase (eNOS) enzyme activity, … delivery of the VEGF-A gene or protein has been shown to restore erectile function in …

Follistatin

Orphan Drug Status Awarded to New Follistatin Gene Therapy for …

www.gate2biotech.com/orphan-drug-status-awarded-to-new-follistatin-gene-therapy-f…

Dec 20, 2012 – Orphan Drug Status Awarded to New Follistatin Gene Therapy for … Many sufferers oferectile dysfunction in parts of the U.S. are able to buy ..

Effects of the activin A-myostatin-follistatin system on aging bone and …

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by M Bowser – ‎2013 – ‎Cited by 30 – ‎Related articles

Nov 21, 2012 – Myostatin levels and the myostatin:follistatin ratio increased with age in … loss ofmyostatin function is associated with increased bone density in … (24 months) mice to activin A,follistatin, and myostatin treatment in vitro. ….. cardiac hypertrophy, enhanced cardiac stress response, and sexual dimorphism.

Myostatin genetic inactivation inhibits myogenesis by muscle-derived …

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by J Tsao – ‎2013 – ‎Cited by 9 – ‎Related articles

Jan 7, 2013 – The genetic inactivation of myostatin in MDSCs was associated with silencing of critical …. Mice were treated according to National Institutes of Health (NIH) ….. Myostatin and follistatin fail to modulate the myogenic differentiation of ….. or muscle-derived stem cells prevent erectile dysfunction in a rat model …

Evaluation of Systemic Follistatin as an Adjuvant to Stimulate Muscle …

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by JW Foley – ‎2010 – ‎Cited by 13 – ‎Related articles

Jun 15, 2010 – … of striated and smooth muscle, leading to skeletal muscle weakness and … Inhibiting myostatin, a negative regulator of muscle growth, has been … AAV8-follistatin to stimulate muscleregeneration and/or hypertrophy.

Follistatin Improves Skeletal Muscle Healing after Injury and Disease …

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by J Zhu – ‎2011 – ‎Cited by 47 – ‎Related articles

Recovery from skeletal muscle injury is often incomplete because of the …. action that follistatin has on muscle cell regeneration, angiogenesis, and fibrosis formation. ….. angiogenesis via the activation of endothelial and smooth muscle cells.

Expression and neural control of follistatin versus myostatin genes …

onlinelibrary.wiley.com/doi/10.1002/dvdy.10306/pdf

by AS Armand – ‎2003 – ‎Cited by 40 – ‎Related articles

Follistatin transcripts could be detected in activated satellite cells as early as the first stages of … Key words: follistatin; myostatin; muscle regeneration; denervation. Received 11 July 2002; …… the smooth-to-striated muscle transi- tion. Dev Biol …

Follistatin induction by nitric oxide through cyclic GMP: a tightly …

jcb.rupress.org › 2006 Archive › 16 January

by A Pisconti – ‎2006 – ‎Cited by 106 – ‎Related articles

Jan 9, 2006 – Subsequently, muscle masses undergo extensive growth in the fetal and ….. In smooth muscle, cGMP may act through protein kinase A, …

Stem Cells

Modulation of Stem Cells Differentiation and Myostatin as an approach …

https://www.researchgate.net/…/235087921_Modulation_of_Stem_Cells_Differentiation

We had shown in Years 1 and 2 that the in vitro myogenic differentiation and myotube formation by MDSC was refractory to modulation by myostatinfollistatin, …

Advances in Stem Cell Therapy for Erectile Dysfunction

www.hindawi.com/journals/aandrol/2014/140618/

by CS Lin – ‎2014 – ‎Cited by 2 – ‎Related articles

Jan 20, 2014 – Abstract. Stem cell (SC) therapy for erectile dysfunction (ED) has been investigated in 35 published studies, with one being a small-scale …

International Journal of Impotence Research – Gene and stem cell …

www.nature.com › Journal home › Archive › Reviews

by W Deng – ‎2005 – ‎Cited by 27 – ‎Related articles

erectile dysfunction, gene therapy, stem cells, endothelial nitric oxide synthase, calcitonin gene-related peptide, superoxide dismutase, RhoA/Rho kinase, …

Stem-cell therapy for erectile dysfunction – ScienceDirect

www.sciencedirect.com/science/article/pii/S2090598X13000880

by M Albersen – ‎2013 – ‎Related articles

Sep 12, 2013 – Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that …

Study Shows Liposuction Byproduct Could Lead to ED Cure | Stem …

www.stemcellsportal.com/study-shows-liposuction-byproduct-could-lead-ed-cure

Mar 25, 2015 – The study, conducted in rats, compares the effectiveness of using a byproduct of liposuction — uncultured stromal vascular fraction (SVF) — with adipose-derived stem cells (ADSCs) cultured in the lab to treat ED caused by injury to the cavernous nerve (CN). … However, no study …

Adult stem cell technology holds hope for erectile dysfunction treatment

www.news-medical.net/…/Adult-stemcell-technology-holds-hope-for-erectiledysfun

Sep 10, 2012 – After more than a decade of short-term cures to erectile dysfunction, most aimed at symptoms rather than the underlying issues of nerve …

Stem Cell Therapy for Erectile Dysfunction: A Critical Review (PDF …

https://www.researchgate.net/…/51525332_Stem_Cell_Therapy_for_Erectile_Dysfunc

dysfunction; nNOS, neuronal. nitric oxide synthase. STEM CELL THERAPY FOR ERECTILE DYSFUNCTION 345. Page 3. Table 1Erectile Dysfunction-Related …

Missing: tropoelastin

[PDF]

Adipose-derived Stem Cells for the Treatment of Peyronie’s Disease?

www.europeanurology.com/…/adipose-derived-stemcells-for-the-treatment-of-peyro…

by CS Lin – ‎2013 – ‎Cited by 10 – ‎Related articles

Adipose-derived Stem Cells for the Treatment of Peyronie’s … evident in the erectile dysfunction(ED) field. … As for elastin, its upregulation by TGF-b in TA-.

Stem cell therapy for erectile dysfunction

www.wjgnet.com/2219-2816/full/v3/i3/272.htm

by E Suzuki – ‎2014 – ‎Related articles

Nov 24, 2014 – Erectile dysfunction (ED) is an importa

Stem cell therapy for voiding and erectile dysfunction

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by M Vaegler – ‎2012 – ‎Cited by 19 – ‎Related articles

Jun 19, 2012 – Stem cell therapy for voiding and erectile dysfunction …. Homing cytokines, such as stromal derived factor-1 (SDF1), have been shown to ..

IGF-1

Insulin-like growth factor-1 restores erectile function in aged rats – NCBI

www.ncbi.nlm.nih.gov/pubmed/18355170

by XY Pu – ‎2008 – ‎Cited by 49 – ‎Related articles

Mar 19, 2008 – INTRODUCTION: Insulin-like growth factor-1 (IGF1) is one of the growth factors … that gene transfer of IGF1 to the penis could improve erectile capacity. … Stimulation; Erectile Dysfunction/drug therapy*; Erectile Dysfunction

Emerging gene and stem cell therapies for the treatment of erectile …

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by A Harraz – ‎2010 – ‎Cited by 21 – ‎Related articles

Feb 16, 2010 – Stem cell therapy has been a topic of interest in more recent years although … Erectile dysfunction (ED) is the persistent inability to achieve or maintain an …. Cavernosal gene transfer ofIGF1 using an adenoviral vector in …

IGF1 Levels Are Significantly Correlated With Sexual Function …

thinksteroids.com › Forums › Medicine › Men’s Health Forum

Sep 17, 2011 – 15 posts – ‎8 authors

An association between low GH levels and erectile dysfunction has been … Given that the half-life ofIGF1 (12–15 h) is significantly longer than …

SDF-1

Recruiting endogenous stem cells: a novel therapeutic approach for …

www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume…

by ZC Xin – ‎2016 – ‎Cited by 2 – ‎Related articles

Transplanted stem cells (SCs), owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED). However …

[PDF]

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in …

www.jsm.jsexmed.org/article/S1743-6095(15)00013-2/pdf

Results: LESW treatment improves erectile function in a rat model of pelvic neurovascular ….. betic EDmodel,11 and that the expression of SDF1, which plays.

SDF1 Gene Variation Is Associated with Circulating SDF1α Level and …

paperity.org/…/sdf1-gene-variation-is-associated-with-circulating-sdf1a-level-and-end…

There was an association between the SDF1 gene rs2297630 SNP A/A genotype, … peripheral vascular disease[10] and patients with erectile dysfunction[16].

HGF

Hepatocyte growth factor-modified adipose tissue-derived stem … – NCBI

www.ncbi.nlm.nih.gov/pubmed/26339935

by T Liu – ‎2015 – ‎Cited by 1 – ‎Related articles

Sep 4, 2015 – Hepatocyte growth factor-modified adipose tissue-derived stem cells improve erectile function in streptozotocin-induced diabetic rats. Liu T(1) …

mp89-03 local delivery of recombinant human hepatocyte growth …

www.jurology.com/article/S0022-5347(16)02752-X/abstract

MP89-03 LOCAL DELIVERY OF RECOMBINANT HUMAN HEPATOCYTE GROWTH FACTORPROTEIN RESCUES ERECTILE FUNCTION BY ENHANCING …

Innovative trends and perspectives for erectile dysfunction treatment: A …

www.sciencedirect.com/science/article/pii/S2090598X16300092

by EA Ismail – ‎2016

May 18, 2016 – This projection indicates a growing need to re-evaluate ED ….. (2015) [38] found that treatment with hepatocyte growth factor-modified ADSCs …

Activin

Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in … – NCBI

www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC)

by JH Jang – ‎2012 – ‎Cited by 9 – ‎Related articles

Jan 25, 2012 – Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in ….. Mulhall JP, Creech SD, Boorjian SA, Ghaly S, Kim ED, Moty A, et al.

eNOS and VEGF

Endothelial Dysfunction in Erectile Dysfunction: Role of the …

onlinelibrary.wiley.com › … › Journal of Andrology › Vol 24 Issue S6 › Abstract

by TJ Bivalacqua – ‎2003 – ‎Cited by 191 – ‎Related articles

Jan 2, 2013 – eNOS -/- mice demonstrate normal erectile fu

Age-related changes in phosphorylation of endothelial nitric oxide …

www.ncbi.nlm.nih.gov/pubmed/16422866

by B Musicki – ‎2005 – ‎Cited by 67 – ‎Related articles

AIM: Aging is associated with erectile dysfunction (ED) attributed to reduced … factor (VEGF) exerts erectile effects and operates via eNOS phosphorylation in …

Endothelial nitric oxide synthase gene therapy for erectile dysfunction.

www.ncbi.nlm.nih.gov/pubmed/16378511

by TJ Bivalacqua – ‎2005 – ‎Cited by 27 – ‎Related articles

Curr Pharm Des. 2005;11(31):4059-67. Endothelial nitric oxide synthase gene therapy for erectile dysfunction. Bivalacqua TJ(1), Musicki B, Usta MF, Champion …

Vascular endothelial growth factor restores erectile function through …

www.ncbi.nlm.nih.gov/pubmed/15592104

by M Yamanaka – ‎2005 – ‎Cited by 61 – ‎Related articles

J Urol. 2005 Jan;173(1):318-23. Vascular endothelial growth factor restores erectile functionthrough inhibition of apoptosis in diabetic rat penile crura.

Tropoelastin

Erectile dysfunction in the type II diabetic db/db mouse: impaired …

www.ncbi.nlm.nih.gov/pubmed/18326798

by IP Luttrell – ‎2008 – ‎Cited by 35 – ‎Related articles

Mar 7, 2008 – Erectile dysfunction in the type II diabetic db/db mouse: impaired … mRNA levels fortropoelastin, fibrillin-1, and alpha1(I) collagen were …

Disorganization of Elastin Matrix Mediates Erectile Dysfunction …

https://iths.pure.elsevier.com/…/disorganization-of-elastin-matrix-mediates-erectiledy

DESCRIPTION (provided by applicant): The outer layer of the corpus cavernosum, the tunica albuginea, is rich in elastic fibers and has the capacity to expand in …

This trial showed that Functional Electrical Stimulation therapy may improve erectile function and quality of life in men with ED.

An initial study on the effect of functional electrical stimulation in …

https://www.nature.com › international journal of impotence research › articles

May 22, 2018 – Functional electrical stimulation (FES) therapy has shown a high regenerative … and increased mental stress, making ED a major quality of life (QoL) issue [2]. … multiple sclerosis, prostatectomy); hypogonadism (total testosterone < 300 ….. Nature asia · Nature China · Nature India · Nature Japan · Nature .

Bioelectrical Stimulation + Stem Cell Composition Mix for Erectile Dysfunction

Bioelectrical Stimulation + Stem Cell Composition Mix for Erectile Dysfunction

This study is not yet currently recruiting participants. (see Contacts and Locations)

Verified July 2016 by MyoStim ED Leonhardt Ventures 

Sponsor:

MyoStim ED a Leonhardt Ventures Co. 

Collaborator:

Harbor UCLA LABioMed

Information provided by (Responsible Party):

Howard Leonhardt, Executive Chairman MyoStim ED Leonhardt Ventures 

ClinicalTrials.gov Identifier:

First received:  TBD

Last updated: TBD

Last verified:  July 2016

  • Full Text View

  Purpose

Bioelectric stimulation control of protein releases + Autologous Fat Derived Stem Cell Mix Composition treatment of ED.

To assess safety and primary efficacy of bioelectric stimulation of SDF-1, Follistatin, IGF-1, HGF, EGF, eNOS, VEGF, Activin A+B, Tropoelastin + stem cell  based cocktail infusion in refractory ED.

To investigate the success rate and durability of success of using this new therapy in management of moderate and severe cases of erectile dysfunction.

Condition

Intervention

Phase

Erectile Dysfunction

Procedure: liposuction for retrieval of own stem cells from fat cells + bioelectric stimulation delivery

Phase 2

Study Type:

Interventional

Study Design:

Allocation: Randomized

Endpoint Classification: Safety/Efficacy Study

Intervention Model: Crossover Assignment

Masking: Open Label

Primary Purpose: Treatment

Official Title:

BioStim ED – Phase 1 Study of Bioelectric Stimulation + Stem Cell Based Mix Composition in Men With Erectile Dysfunction

Resource links provided by NLM:

MedlinePlus related topics: Erectile Dysfunction

U.S. FDA Resources 

Further study details as provided by MyoStim ED Leonhardt Ventures 

Primary Outcome Measures:

  • Adverse Events that occur during or after the procedure to measure safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ] to assess efficacy and safety of injection of stem autologous stem cells in penis of ED patients

Estimated Enrollment:

30

Study Start Date:

TBD

Estimated Study Completion Date:

May 2018

Estimated Primary Completion Date:

TBD – (Final data collection date for primary outcome measure)

Arms

Assigned Interventions

Active Comparator: bioelectric stimulation via bandage wrap + stem cell mix composition infusion in penis

Treatment bioelectric stimulation + adipose derived cells based mix composition into penis experimental; randomised

Procedure: liposuction for retrieval of own stem cells from fat cells, bioelectric stimulation applied. 

No Intervention: control arm

  Eligibility

Ages Eligible for Study:  

40 Years to 70 Years   (Adult, Senior)

Genders Eligible for Study:  

Male

Accepts Healthy Volunteers:  

No

Criteria

Inclusion Criteria:

  • Male 40 years old and older suffering from moderate to sever erectile dysfunction –

Exclusion Criteria:

  • Inability to give informed consent or attend follow up
  • Severe diabetic neuropathy (to be defined ? Charcot joints, diabetic ulcers?) or other neuropathic disease
  • Viral disease from infectivity viewpoint
  • Major penile fibrosis or severe Peyronie’s disease
  • Severe primary large vessel ED (defined as PSV less than 15cm/s after ICI)
  • Severe primary venous leakage ED (defined as EDV more than 10cm/s after ICI)
  • Prior systemic chemotherapy, or radiotherapy to donor or recipient area
  • Not in potentially active sexual relationship
  • Age less than 40 or over 70

  Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies. 

Please refer to this study by its ClinicalTrials.gov identifier: =

Contacts

Locations

Sponsors and Collaborators

MyoStim ED Leonhardt Ventures

Harbor UCLA LABIOMED

Investigators

Study Director:  TBD 

  More Information

Responsible Party:

TBD 

ClinicalTrials.gov Identifier:

Other Study ID Numbers:

Study First Received:

TBD 

Last Updated:

TBD 

Health Authority:

TBD 

Keywords provided 

stem cells injections

erectile dysfunction

bioelelectric stimulation 

Additional relevant MeSH terms:

Erectile Dysfunction

Sexual Dysfunction, Physiological

Genital Diseases, Male

Sexual Dysfunctions, Psychological

Mental Disorders

ClinicalTrials.gov processed this record **** TBD 

Erectile function restored with cell therapy in preclinical model

https://bjui-journals.onlinelibrary.wiley.com/doi/abs/10.1111/bju.14631

WINSTON-SALEM, NC (US), August 2019 – Prostate cancer is the most common cancer in men, with radical prostatectomy as a commonly chosen course of action. The reported rate of erectile dysfunction after prostate surgery for cancer is reportedly as high as 90 percent. When first- and second-line treatments for erectile dysfunction fail, implantable penile prostheses are utilized.
However, there are potential limitations to all of these treatments.
Cell therapy has provided promising outcomes for improvements in erectile function in pre-clinical studies. Stem cells have been proposed as a treatment for erectile dysfunction, mainly from three sources: adult, perinatal and fetal tissues. Stem cells derived from fat, bone marrow, urine, placentas, umbilical cords and amniotic fluid have shown some level of improvement in erectile dysfunction models. 
 
Although each stem cell population has been separately evaluated in various short (two weeks) or middle-term (four to six weeks) preclinical in vivo experiments, one important question should be addressed: whether each stem cell population from different sources achieves similar outcomes for recovery in a severe erectile dysfunction model after long-term follow-up. 
 
In this study, researchers at the Wake Forest Institute for Regenerative Medicine tested the therapeutic impact of three cell types – amniotic fluid-derived stem cells, umbilical vein endothelial cells and adipose-derived stem cells — to determine the long-term therapeutic effect on erectile function recovery in a rat model of dual neurovascular-injury erectile dysfunction. The cells were injected intracavernously into the penile tissue. Saline injection served as a control group. Erectile function and analyses of penile tissues were assessed 12 weeks later.
 
All three cell treatment groups showed a significant improvement in erectile function, as compared to the saline-injected control group. However, the amniotic fluid-derived stem cells had a better recovery potential.
 

The researchers concluded that the long-term therapeutic effect achieved promising outcomes in restoring erectile function and improving neuromuscular regeneration and endothelial repair in vivo, which may provide an alternative approach to the treatment of patients with ED after radical prostatectomy or severe pelvic neurovascular injury.

Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study

Abstract

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients’ adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment.
 


Adipose-derived stem cell-derived exosomes ameliorate erectile dysfunction in a rat model of type 2 diabetes

 

Comparison of the therapeutic effects of adipose‑derived and bone marrow mesenchymal stem cells on erectile dysfunction in diabetic rats

Abstract

The aim of the present study was to compare the effects of adipose‑derived mesenchymal stem cell (ADSC) and bone marrow mesenchymal stem cell (BMSC) transplantation into the corpora cavernosa of diabetic rats with erectile function. ADSCs and BMSCs were isolated and identified by flow cytometry. Rats with streptozocin‑induced diabetes were screened using apomorphine to obtain a rat model of diabetic erectile dysfunction, followed by transplantation of ADSCs and BMSCs into the corpora cavernosa. Two weeks later, the rats were again injected with apomorphine, the intracavernous pressure (ICP) and mean arterial pressure (MAP) of the penile tissue were measured, and the corpus cavernosum tissues were harvested. Angiogenic endothelial nitric oxide synthase (eNOS) expression was detected by western blotting and immunofluorescence analysis. The blood vessels in the corpus cavernosum were observed following hematoxylin and eosin (H&E) staining, and the expression of collagen was detected by Sirius Red staining. The cellular ultrastructure was examined by transmission electron microscopy. Intracavernous injection of ADSCs significantly increased ICP and ICP/MAP. Western blotting and immunofluorescence results revealed that ADSC treatment improved the expression of eNOS in the penile tissue of diabetic rats. The H&E staining results demonstrated that ADSC treatment promoted revascularization of the corpus cavernosum, and the results of Sirius Red staining revealed that ADSC treatment reduced penile collagen in diabetic rats. Transmission electron microscopy examination revealed that the ultrastructure of the tissues in the ADSC‑treated group was more complete compared with that in the untreated diabetic model group. In conclusion, ADSCs were found to be more effective compared with BMSCs in treating diabetes‑related erectile dysfunction.
 
Stem cells shown to restore erection capability in men with erectile dysfunction

MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury

 

Stem cell therapy in diabetic men with erectile dysfunction: a step closer to safe and effective regenerative technology

 
 

A Systematic Review of Human Trials Using Stem Cell Therapy for Erectile Dysfunction

Erectile Dysfunction Stem Cell Therapy Shows Positive Results in Early Trial

Cavernous nerve regeneration by biodegradable alginate gel sponge sheet placement without sutures

Erectile dysfunction: Stem cell therapy restores sexual function in phase I trial https://www.medicalnewstoday.com/articles/316555

 

Correction of Diabetic Erectile Dysfunction with Adipose Derived Stem Cells Modified with the Vascular Endothelial Growth Factor Gene in a Rodent Diabetic Model

Abstract

The aim of this study was to determine whether adipose derived stem cells (ADSCs) expressing vascular endothelial growth factor (VEGF) gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED) model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then screened by apomorphine (100 µg/kg). Five groups were used (n = 12/group)–Group 1 (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1–G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2). ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.

Safety and Potential Therapeutic Effect of Two Intracavernous Autologous Bone Marrow Derived Mesenchymal Stem Cells injections in Diabetic Patients with Erectile Dysfunction: An Open Label Phase I Clinical Trial

 
 

Intracavernous injection of size-specific stem cell spheroids for neurogenic erectile dysfunction: Efficacy and risk versus single cells

Landmark Results for CaverStem® Procedure Published in Journal of Translational Medicine to Create Paradigm Shift in Treatment of Erectile Dysfunction

Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions

Mesenchymal Stem Cells Treatment for Erectile Dysfunction in Diabetic Rats

Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis

 

Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury

Abstract

Erectile dysfunction (ED) is an important kind of postoperative complication of pelvic surgery that affects patients’ quality of life. Transplantation of mesenchymal stem cells (MSC) has been found to alleviate ED caused by cavernous nerve injury (CNI) in rats. However, little is known about whether induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have a therapeutic effect on CNI ED. We established an ED model on rats and evaluated the effect of iMSC on it.
Methods: Eight-week-old male Sprague-Dawley rats were assigned to four groups and received following operation: sham operation (sham group); bilateral CNI and phosphate-buffered saline (PBS) injections (PBS group); bilateral CNI and adipose-derived mesenchymal stem cells transplantation (adMSC group); or bilateral CNI and iMSC injection (iMSC group). After therapy, the cavernous nerve was stimulated by electricity and the intracavernous pressure (IAP)/mean arterial blood pressure (MAP) was measured. The endothelial and smooth muscle tissue in the penis was assessed histologically with Masson’s trichrome stain. Immunofluorescence/immunohistochemical stains were applied for the detection of nNOS, vWF, eNOS, SMA, Desmin, S100β, and caspase-3. Nude rats CNI ED model was established for the evaluation of iMSC longevity and differentiation capacity. The paracrine factors were assessed by real-time PCR.
Results: Transplantation of iMSC significantly restored the IAP/MAP in this CNI ED model and showed long-term effects. It could rescue the expression of vWF, eNOS, SMA, and Desmin, which indicated the alleviation of endothelial and smooth muscle tissues of the penis. iMSC therapy also could increase the expression of nNOS in the cavernosum and S100β in the major pelvic ganglia (MPG) which contributed to the erectile function. Moreover, the level of BAX and caspase-3 were reduced and Bcl-2 was increased, which indicated the anti-apoptosis effects of iMSC. The iMSC showed little transdifferentiation and exerted their function by activating the secretome of the host.
Conclusion: Transplantation of iMSC significantly improved ED induced by CNI. The iMSC may exert their effects via paracrine factors and may be a promising therapeutic candidate for treating CNI ED in the future.
An initial study on the effect of functional electrical stimulation in erectile dysfunction: a randomized controlled trial
Endothelial nitric oxide synthase gene therapy for erectile dysfunction.