Previously mentioned (https://uroprolo.blogspot.com/2023/05/blog-post.html), Regeneration Therapies applied to Erectile Dysfunction (ED) in men can be categorized into three major types:
i. Low-Intensity Shockwave Therapy (LiSWT)
ii. Platelet-Rich Plasma (PRP)
iii. Stem Cell Therapy (SCT) and Stromal Vascular Fraction (SVF)
We have already discussed Low-Intensity Shockwave Therapy and Platelet-Rich Plasma (https://uroprolo.blogspot.com/2023/06/prp.html).
This time, we will delve into Stem Cell Therapy (SCT) and Stromal Vascular Fraction (SVF).
Stem Cell Therapy (SCT)
1.Treatment Mechanisms
There are two main theories:
a. Building Block Theory: Injected stem cells stimulate self-renewal and differentiate to replace diseased tissues.
b. Paracrine Theory: Stem cells reduce inflammation and cell apoptosis, drive blood vessel formation, and neuritogenesis by releasing growth factors and chemokines.
2.Stem Cell Sources
There are two major categories:
a. Embryonic (Placental and Umbilical Cord Blood) Source: While derived from birth waste, it raises ethical concerns and tumor risks.
b. Mesenchymal (Bone Marrow) Source
3.Representative Research - Intra-cavernous Stem Cell Injection [INSTIN]
Twelve patients with erectile dysfunction (ED) following radical prostatectomy for early-stage prostate cancer, unresponsive to maximal medication therapy, participated in intra-cavernous stem cell injection research.
The study is currently in its second phase.
a.Phase 1 Research Goals:
Evaluate tolerance and safety, understand dose variations, and assess treatment efficacy.
Patients were divided into four equal groups, receiving one of four doses of bone marrow stem cells (2 × 10^7, 2 × 10^8, 1 × 10^9, 2 × 10^9).
Effectiveness was assessed using the International Index of Erectile Function (IIEF-15) and the Erection Hardness Score (EHS).
Average age: 63.6 ± 4.2 years, time from surgery to injection: 22.9 ± 9.8 months.
Research Findings:
All patients tolerated the injection.
No adverse reactions occurred throughout the study.
The most common side effect was mild temporary post-injection pain, which did not persist.
At 6 months, significant improvements were observed in erectile function (EF) compared to baseline (17.4±8.9 vs 7.3±4.5, P=0.006) and Erection Hardness Score (EHS) (2.6±1.1 vs 1.3±0.8, P=0.008).
The optimal dosage was determined to be 1 × 10^9.
b.Phase 2
Six additional patients who received a dose of 1 × 10^9 cells were added, and the clinical parameters of the initial 12 patients were monitored for updates.
After 6 months, there was a significant improvement in erectile function (EF) (18±8.3 vs 3.7±4.1, p=0.035).
The initial 12 patients were followed for an average of 61.1±11.7 months, and no prostate cancer recurrence was observed.
The study is still ongoing.
Stromal Vascular Fraction (SVF)
1.Treatment Mechanisms and Sources
SVF is a heterogeneous mixture derived from liposuction aspirate treated with digestive enzymes.
SVF not only includes adipose derived stem cells, but also the associated progenitor cells, preadipocytes, and lymphocytes, creating an environment that provides synergistic activity.
This can drive cellular adhesion, tissue remodeling, and cellular differentiation.
2.Representative Research
Tissue Genesis Phase 2a Trial
Thirty males with erectile dysfunction (ED) were randomly assigned in a 2:1 ratio to the experimental group or the control group.
The experimental group had 60–120 cm^3 of adipose tissue extracted.
Quality checks on SVF were conducted before injection, including measurements of cell concentration and viability, Gram staining, and endotoxin testing.
Up to 30 cm^3 of SVF was injected into the corpora cavernosa through a 21-gauge needle within 2-4 minutes, followed by the application of a compression band at the base of the penis for 10-15 minutes.
Patients were assessed daily for 72 hours and then at 1, 2, 6, 12, 24, and 26 weeks postoperatively, followed by assessments every 6 months until 36 months postoperatively.
The control group was allowed to cross over to the experimental group or exit the study at 9 months.
The treatment group was followed for 36 months.
At 6 months, an improvement in IIEF-5 was observed, and safety was monitored for 36 months, with no significant adverse reactions.
The treatment group showed a sustained improvement of 2-4 points in IIEF-5 from baseline at 3 months, while the control group showed no improvement after 6 months.
The Phase 2b study (Tissue Genesis Phase 2b Trial) is currently underway, including a cross-comparison (treatment and control groups) and focusing on moderate erectile dysfunction (IIEF 11-22).
Efficacy will be observed for up to 12 months.
Summary:
Research on stem cell/stromal vascular fraction therapy for erectile dysfunction is still limited, with mostly small-scale (4-30 cases), non-randomized, open-label (non-blinded) trial studies.
However, current research results affirm its therapeutic effectiveness and high safety.
If larger-scale studies demonstrate its treatment potential and standardized treatment processes are established, it is believed that this therapy could become a boon for a wide range of patients and an extremely promising star of tomorrow!
References:
AUA update series, volume 41, Lesson 28
https://auau.auanet.org/US2022-28
https://pubmed.ncbi.nlm.nih.gov/26439886/
https://linkinghub.elsevier.com/retrieve/pii/S0302-2838(15)00934-3
https://pubmed.ncbi.nlm.nih.gov/28753830/
https://www.eu-focus.europeanurology.com/article/S2405-4569(17)30160-8/fulltext
Stem Cell Therapy for Erectile Dysfunction
https://pubmed.ncbi.nlm.nih.gov/29631980/
https://pubmed.ncbi.nlm.nih.gov/31196678/
https://www.eu-focus.europeanurology.com/article/S2405-4569(19)30154-3/fulltext
