Stem Cells in Clinical Trials for Pelvic Floor Disorders: a Systematic Literature Review

Authors: Stefano Manodoro, Matteo Frigerio, Marta Barba, Sara Bosio, Luigi Antonio de Vitis, Anna Maria Marconi

Abstract

Pelvic floor disorders (PFDs) — including stress urinary incontinence, anal incontinence, and pelvic organ prolapse — occur when muscles, ligaments, or nerves that support the pelvic organs are weakened or damaged. Current treatments (pelvic floor rehab, surgery, implants) help many people but often leave room for improvement. Stem cell (SC) therapy is being studied as a possible regenerative approach to strengthen or repair sphincter and pelvic muscle damage.

This article summarizes the clinical trial evidence available up to November 7, 2020. We found 11 prospective clinical studies: 7 focused on stress urinary incontinence and 4 on anal incontinence. No clinical trials for prolapse repair using culture-expanded stem cells were found. The studies used different cell sources (adipose tissue, skeletal muscle, umbilical cord blood), delivery methods, and outcome measures. Overall, stem cell injections appeared safe in the short term, with only minor side effects mostly tied to the cell-harvest site. However, the studies were small and very different from each other, so there is not yet clear proof that stem cell therapy gives consistent, meaningful benefit for pelvic floor disorders. Larger, standardized, controlled trials are needed.

Key points

• Number of clinical studies included: 11 (7 for stress urinary incontinence, 4 for anal incontinence).
• Total patients in urinary incontinence trials: 99. Total patients in anal incontinence trials: 66 (including 10 men).
• Cell sources used: adipose-derived mesenchymal stem cells (fat), muscle-derived (skeletal muscle) cells, and umbilical cord blood cells.
• Injected cell counts varied widely: from ~1.8 × 10^6 up to 1 × 10^8 cells depending on study and source.
• Safety: no serious adverse events directly caused by injections were reported; minor complications included hematomas at harvest sites, brief dysuria, urinary tract infection, and local erythema.
• Efficacy: mixed. Some single-arm studies (especially those using muscle-derived cells) reported symptom improvement; randomized controlled trials using adipose-derived cells showed little or inconsistent benefit compared to placebo.

Why this matters for stem cell banking and regenerative health

• Autologous cell therapy (using a person's own cells) is common in these trials. If stem cells are banked earlier in life (for example, cord blood or cord tissue at birth), they may be younger and potentially more robust for future regenerative uses.
• Different cell sources behave differently. Muscle-derived cells showed more promising results in small studies for sphincter repair, whereas adipose-derived cells showed weaker or inconsistent benefits in randomized trials. This suggests that the type of stored tissue and its processing matter for regenerative outcomes.
• For families considering banking cord blood, cord tissue, or planning future autologous cell use, these trials show a potential therapeutic pathway but underline the need for well-designed trials before routine clinical use for pelvic floor repair.

Introduction — plain-language explanation

Pelvic floor disorders happen when the support structures of the pelvic organs weaken or are injured. Common causes include childbirth-related muscle and nerve injury. Symptoms can include urine leakage with coughing or exercise (stress urinary incontinence) and accidental stool leakage (anal incontinence). These conditions reduce quality of life for many people.

Stem cells are cells that can either become multiple types of tissue or release signaling molecules (growth factors and cytokines) that help nearby tissue repair itself. In laboratory and animal studies, researchers have seen muscle and nerve repair after injections of muscle-derived or mesenchymal stem cells. The hope is that injecting stem cells into damaged sphincters or surrounding tissue can rebuild muscle and restore function by two main mechanisms:

• Direct replacement or fusion with muscle cells (myogenic differentiation).
• Paracrine support: stem cells release growth factors that recruit the body's own repair processes (angiogenesis, nerve support, anti-inflammatory signals).

Methods (summary of how the review was done)

• The authors searched PubMed, Scopus, Cochrane Library, and Web of Science through November 7, 2020. Preclinical (animal) studies, reviews, abstracts, and studies that did not actually isolate and culture stem cells were excluded.
• Two reviewers screened titles, abstracts, and full texts. Data were extracted on study design, cell source, number of cells, delivery method, number of patients, and clinical outcomes. Because the trials used different designs and measurements, the authors did not pool data into a meta-analysis.

Results — simplified summary with clinical data

Study selection and scope

• Total records screened: 3,232; after exclusions and full-text review, 11 clinical studies met inclusion criteria.
• Focus: 7 studies on stress urinary incontinence (SUI) and 4 on anal/fecal incontinence. No clinical trials using culture-expanded stem cells for pelvic organ prolapse repair were found.

Stress urinary incontinence (7 studies, 99 patients total)

• Cell sources: adipose-derived (fat) in 3 studies; muscle-derived cells in 3 studies; umbilical cord blood cells in 1 study.
• Injection routes: transurethral (through the urethra), periurethral (around the urethra), transvaginal periurethral.
• Injected cell counts ranged from 1.8 × 10^6 to 5.0 × 10^7 cells.
• Safety: no serious treatment-related adverse events. Minor issues included hematomas at fat harvest sites (2 cases), transient dysuria (3 cases), urinary tract infection (2 cases), and pain leading to withdrawal in 2 patients.
• Outcomes: objective measures (pad tests, cough stress tests) often improved in many patients, but subjective questionnaires (patient-reported quality of life) improved in some studies and not in others. Studies using muscle-derived cells or cord blood sometimes reported better patient satisfaction; adipose-derived cells showed mixed or limited benefit.
• Durability: some apparent benefits decreased over time (e.g., recurrence of leakage in some patients by 24 months in one study).

Anal/fecal incontinence (4 studies, 66 patients total)

• Study designs included two single-arm prospective studies and two randomized controlled trials.
• Cell sources: adipose-derived in two trials; muscle-derived in two trials.
• Delivery: direct injections into the external or internal anal sphincter, sometimes during surgical repair (sphincteroplasty).
• Cell numbers: from 6 × 10^6 to 1 × 10^8 cells depending on study.
• Safety: generally safe; a few minor harvest-site complications (hematoma, erythema) reported.
• Outcomes: single-arm studies with muscle-derived cells reported improvements in symptoms, quality of life, manometry, or EMG activity. Randomized trials using adipose-derived cells showed inconsistent benefit; one RCT found no significant difference between cells and placebo, and another found small changes in muscle volume or electrical activity but not clear clinical improvement.

Discussion — what the evidence shows and practical implications

Safety

Across small clinical trials, injections of culture-expanded stem cells to treat pelvic sphincter defects appear to be safe in the short term, with only minor complications mainly at the harvest site.

Efficacy and variability

• Results are mixed. Some small, uncontrolled studies reported symptom improvement, particularly with muscle-derived cells. However, better-quality randomized trials using adipose-derived cells did not show consistent clinical benefit compared to placebo.
• Trials differ in patient selection (type and cause of incontinence), cell source, cell dose, processing methods, injection site, and outcome measures. This heterogeneity makes it hard to say whether stem cell therapy works reliably.

What this means for stem cell banking and regenerative medicine

• Source matters: muscle-derived cells and cord blood were associated with more encouraging single-arm results in some studies, while adipose-derived cells were less consistent in randomized trials. For families considering stem cell banking, this highlights that the type of tissue preserved (cord blood, cord tissue, or adipose-derived cells later in life) may affect future therapeutic options.
• Timing and cell age: cells collected and banked at birth (cord blood/tissue) are younger and may have different regenerative properties than cells harvested later in life. Banking provides an autologous source that could be safer immunologically and possibly more potent for future regenerative uses.
• Practicality: cell harvesting, expansion, and implantation are complex and costly. Standardized methods, dosages, and delivery routes are not yet established.

Limitations in the current evidence

• Small sample sizes and short follow-up in many studies.
• Heterogeneous designs prevented quantitative pooling of results.
• Lack of standardized cell-processing and outcome reporting across trials.

Recommendations for future research

• Larger randomized controlled trials with standardized cell sources, doses, and delivery techniques.
• Longer follow-up to assess durability of response.
• Head-to-head comparisons of different cell sources (muscle-derived vs adipose-derived vs cord-derived) to clarify which is most effective for sphincter repair.
• Clearer reporting of harvesting morbidity and costs to weigh risks and benefits for patients and for decisions around banking.

Conclusions

Clinical trials to date suggest stem cell injection for pelvic floor sphincter problems is safe in the short term, but the evidence for clear, consistent benefit is weak and mixed. There is no convincing proof yet that stem cell therapy should replace or augment standard treatments outside clinical trials. For people considering stem cell banking, these results support the potential future value of having autologous cells available, but more high-quality research is needed to define which stored cell types and treatments will be truly effective for pelvic floor regeneration.

Selected clinical studies and sources (examples)

• Autologous adipose-derived cell trials for stress urinary incontinence: Kuismanen K et al., 2014; Arjmand B et al., 2017; Garcia-Arranz M et al., 2020. (Small studies with mixed outcomes.)
• Muscle-derived cell trials for stress urinary incontinence and anal incontinence: Carr LK et al., 2008; Sharifiaghdas F et al., 2016 & 2019; Frudinger A et al., 2018; Romaniszyn M et al., 2015. (Some single-arm studies showed symptom improvement.)
• Randomized controlled trials for fecal incontinence with adipose-derived cells: de la Portilla F et al., 2020; Sarveazad A et al., 2017. (Inconsistent benefit versus placebo.)

References

Full list of references and supplementary materials are available in the original systematic review (Reproductive Sciences, 2021; see PMID: 34596887 / PMCID: PMC9110489).

Data availability

The datasets analyzed in the review are available from the corresponding author of the original paper on request.