MSC-based therapy in female pelvic floor disorders — simplified review

Authors: Yizhen Sima & Yisong Chen (original review published Cell & Bioscience, 2020)

This cleaned, plain-language summary keeps the original article's structure, main findings, clinical data, and key sources, and explains why the research matters for stem cell preservation, longevity, and regenerative medicine.

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• Mesenchymal stem/stromal cells (MSCs) are adult cells found in many tissues that can help repair damaged tissue.
• Pelvic floor disorders (PFDs) — including stress urinary incontinence (SUI), fecal incontinence (FI), and pelvic organ prolapse (POP) — are common and reduce quality of life. Current treatments have limits (recurrence, complications).
• Research shows MSCs (from fat, bone marrow, uterus lining, muscle, umbilical cord, urine, etc.) can reduce symptoms and help tissue repair in animal models and small human trials.
• MSCs appear to act mainly by secreting helpful molecules (a “secretome” including exosomes) and by reducing inflammation, rather than by permanently becoming new tissue cells.
• MSC-based approaches (cell injections, cells on scaffolds/meshes, or cell-derived secretions) are promising but still experimental. More standardization and larger clinical trials are needed.

Why this matters for stem cell banking and longevity: banking high-quality MSC sources (e.g., umbilical cord, adipose tissue, placenta) and their derivatives (exosomes) can support future regenerative treatments aimed at tissue repair, maintaining function with age, and reducing the impact of degenerative conditions.

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• Pelvic floor disorders (PFDs) include urinary incontinence, fecal incontinence, and pelvic organ prolapse. They are common — for example, urinary incontinence affects roughly 17% of adults and pelvic floor problems affect ~25% of women over 20 in the U.S. (see ref. 1).
• Causes include childbirth, aging, menopause, obesity, chronic coughing, constipation, and connective-tissue changes that weaken support structures.
• Non-surgical options (exercise, pessaries, biofeedback) relieve symptoms but often do not repair structure. Surgical repair can have complications (mesh problems, recurrence).
• MSCs are a leading cell type in regenerative medicine because they are:
• Available from many tissues (fat, bone marrow, umbilical cord, placenta, endometrium, urine, muscle),
• Able to support tissue repair,
• Immune-modulating (can reduce excessive inflammation),
• Suitable for combining with biomaterials (meshes/scaffolds) for tissue engineering.

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• MSCs were first found in bone marrow; later, similar cells were found in fat, umbilical cord, placenta, endometrium (uterine lining), muscle, skin, dental pulp, and even urine.
• The International Society for Cellular Therapy set simple lab criteria (2006) to define MSCs (adherence in culture, certain surface markers, ability to become bone, fat, cartilage in vitro), but there is no single unique marker. MSCs from different tissues behave differently.
• Two important concepts:

• Therapeutic actions often come from the MSC secretome — molecules and small vesicles (exosomes) secreted by MSCs that communicate with local cells and immune cells.
• MSCs may be better described as “medicinal signaling cells” because their benefit is often through signaling, not long-term cell replacement.

Implication for banking: preserving different tissue-derived MSCs (and/or their secreted products) could provide different therapeutic options; standardized collection, processing and storage is critical.

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Main sources studied and practical points:

• Bone marrow-derived MSCs (BM-MSCs)
• Well-studied; historically the "gold standard".
• Low frequency in marrow; harvesting is invasive and painful.

• Adipose-derived stem cells (ADSCs)
• Abundant in fat; liposuction harvest is commonplace.
• Can be obtained as autologous cells in a single procedure (some clinical reports).
• Most widely investigated for SUI and FI.

• Muscle-derived stem cells (MDSCs) / Autologous muscle-derived cells (AMDCs)
• From skeletal muscle biopsy.
• Used in several clinical trials for intrasphincteric injection (SUI, FI).
• Can include a mixed population of myogenic cells and fibroblasts.

• Endometrial MSCs (eMSCs)
• From uterine lining (endometrium). Easy to access by biopsy, even post-menopause.
• Good candidate for seeding meshes and scaffolds because of anti-inflammatory and remodeling effects.

• Umbilical cord and umbilical cord blood MSCs (UC-MSCs, UCB-MSCs)
• Non-invasive at birth; rich source for banking.
• Good proliferative and paracrine profiles.

• Placenta-derived MSCs
• Immune-modulatory with low immunogenicity — attractive for allogeneic use.

• Urine-derived stem cells (USCs)
• Non-invasive collection.
• Show MSC-like properties and potential for urological reconstruction.

Takeaway for stem cell banking: umbilical cord, placenta, and adipose tissue are especially valuable sources to cryopreserve because they are relatively easy to collect and have shown therapeutic potential.

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• Homing / migration

• MSCs can travel to injured pelvic tissues after systemic delivery (e.g., intravenous) or local injection.
• In some animal studies, IV-injected MSCs accumulated in pelvic organs after simulated childbirth injury.
• Homing helps target widespread pelvic damage that a single injection site cannot cover.

• Paracrine effects — the dominant mechanism

• MSCs release a complex mix of proteins, RNAs, growth factors, and extracellular vesicles (exosomes) that:
• Protect and support injured muscle and connective tissue (trophic support),
• Stimulate new blood vessel formation (angiogenesis),
• Improve collagen production and extracellular matrix remodeling,
• Modulate immune responses and reduce harmful inflammation.

• Immune modulation

• MSCs can decrease harmful immune activation and shift macrophages toward a healing type (M2).
• This helps reduce foreign body response (FBR) to implanted meshes and improves biocompatibility.

Important note: In many studies injected MSCs are detectable only briefly in tissues; their long-term benefit seems to come from early secreted signals rather than permanent engraftment.

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• Many small-animal (mostly rat) models have tested MSC therapy for SUI, FI, and POP using different injury models (sphincter damage, vaginal dilation, pudendal nerve injury).
• Typical delivery: periurethral (local) injection, or systemic (IV) injection to study homing.
• Repeated findings across studies:
• MSCs or MSC-derived exosomes improved leak-point pressures, bladder capacity, and sphincter or anal pressures in animal models.
• Histology often shows more muscle fibers, better vascularization, less fibrosis.
• Exosomes and conditioned media (acellular therapies) can reproduce many benefits, supporting the paracrine hypothesis.
• Tissue-engineered meshes seeded with eMSCs or other MSCs showed reduced inflammatory response and better tissue integration in animal models.
• Safety in animals: short-term studies generally show good tolerance; some larger-animal studies (e.g., dog model) up to 9 months showed no major safety signals.

Examples (selected preclinical highlights):

• Lin et al. (2010): ADSCs improved urinary function in a rat model of childbirth injury [ref. 38].
• Dissaranan et al. (2014): MSC secretome promoted elastin formation and recovery after simulated childbirth injury [ref. 64].
• Liu et al. (2018): ADSC-derived exosomes changed collagen metabolism in fibroblasts from women with SUI (in vitro) — increasing collagen I & TIMPs, decreasing MMPs [ref. 65].
• Ni et al. (2018), Wu et al. (2019): Exosomes from ADSCs or urine-derived stem cells promoted muscle and nerve repair and improved functional incontinence measures in rats [refs. 89, 90].

Implication: Animal data are encouraging, and acellular approaches (exosomes, concentrated conditioned media) are attractive because they avoid some risks of live-cell therapy and may be easier to standardize.

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• POP surgery sometimes uses synthetic meshes to support pelvic organs, but mesh complications (erosion, excessive inflammatory response) have been a major issue.
• Studies combining MSCs (especially eMSCs) with biodegradable or synthetic meshes show:
• Improved integration of the mesh with host tissue,
• Lower inflammatory cytokines and a higher ratio of healing-type macrophages (M2),
• Better biomechanical properties over time in animal models.
• This suggests MSC seeding or MSC-derived factors could make pelvic implants safer and more durable.

Relevance for banking: having MSC sources and protocols for seeding or producing MSC secretome could support personalized tissue-engineering products.

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• The MSC secretome — especially extracellular vesicles (exosomes) — carries proteins, RNAs and signals that can guide repair.
• Advantages of acellular therapy:
• Easier to store and standardize,
• Fewer regulatory/safety concerns associated with live cells,
• Still shows beneficial effects on muscle regeneration, ECM (collagen) regulation, and nerve repair.
• Important findings:
• Exosomes increase collagen synthesis and inhibit collagen-degrading enzymes in fibroblasts from women with SUI [ref. 65].
• Exosomes from ADSCs or USCs supported skeletal muscle satellite cell activation via ERK signaling and improved function in rats [refs. 89, 90].

For stem cell banking: storing conditioned media or exosome preparations (or establishing manufacturing from banked MSCs) could be an efficient route to deliver regenerative therapies in the future.

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Overview:

• Clinical work is preliminary: small Phase I/II trials, pilot studies, and a few randomized controlled trials.
• Most human studies used autologous muscle-derived cells (AMDCs), ADSCs, or adipose-derived regenerative cells injected periurethrally or into sphincters.
• Results are mixed but often show symptom improvement in some patients, with generally tolerable safety profiles. However, placebo responses are common.

Selected clinical results:

• Muscle-derived/autologous myogenic cell trials:
• Multiple small trials reported improvements in incontinence symptoms and quality of life; some long-term follow-up (2–4 years) reported sustained benefit in many patients [refs. 91–95].
• Dose-ranging trials suggested higher cell doses may give better outcomes [ref. 94].

• Adipose-derived cell trials:
• Pilot studies: subjective and objective improvement in some patients with SUI after periurethral injection of autologous adipose-derived cells (with/without a carrier like collagen) [refs. 96, 97].
• Small randomized and blinded trials are limited.

• Fecal incontinence (FI):
• AMDC injections into the external anal sphincter showed reductions in incontinence episodes and good patient satisfaction, though objective physiological measures (manometry, imaging) did not always match symptom improvements [refs. 98, 99].

• Largest randomized, double-blind, placebo-controlled trial to date:
• Jankowski et al. (2018) evaluated autologous muscle-derived cells vs placebo for female SUI.
• Findings: high placebo response made it hard to show a clear benefit; cell therapy was well tolerated. Post-hoc analyses suggested more stringent outcome definitions might better separate true responders [ref. 100].

Barriers in trials:

• Heterogeneous cell types, doses, and delivery methods.
• Difficulty tracing injected cells in humans.
• High placebo response and variable measurement endpoints.
• Injection precision can be limited (studies in animals suggested some inaccuracy of intrasphincteric injection).

Bottom line: Early human data suggest MSC-based approaches can be feasible and safe, with benefit in some patients, but larger, standardized RCTs are needed.

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• Most small trials and animal studies report good short-term safety.
• Allogeneic MSCs can elicit immune responses in some contexts — MSCs are generally immune-evasive rather than completely immune-privileged [ref. 71].
• Long-term safety data are limited; rigorous monitoring and standardization are essential.

For banking: strict quality control, testing for contaminants, genomic stability, and clear documentation of provenance and processing are crucial for clinical safety.

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• MSCs (and their secretions) show promise for treating pelvic floor disorders by promoting repair, reducing harmful inflammation, and improving mesh integration.
• Most benefits appear to come from MSC signaling (secretome/exosomes) rather than long-term engraftment.
• The field is still experimental: more basic work (cell identity, biomarkers), standardized manufacturing, and large randomized clinical trials are needed.
• Acellular therapies (exosomes, conditioned media) are a particularly attractive next step because they may be safer and easier to standardize.

Practical message for stem cell banking and longevity:

• Banking clinically useful MSC sources (umbilical cord, placenta, adipose tissue, endometrium) provides raw material for future regenerative treatments that can preserve tissue function with aging and after injury.
• Properly stored MSCs or their secreted products may one day be used to:
• Repair pelvic floor tissues damaged by childbirth or aging,
• Reduce inflammation and fibrosis associated with implants,
• Support muscle and nerve repair to maintain continence and pelvic support,
• Contribute to broader strategies for healthy aging and functional longevity.
• To realize these benefits, standardized collection, processing, characterization, and storage protocols are essential — both for therapeutic consistency and regulatory approval.

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• MSC(s): Mesenchymal stem / stromal cells
• ADSCs: Adipose-derived stem cells
• BM-MSCs: Bone marrow-derived MSCs
• eMSCs: Endometrial MSCs
• AMDCs: Autologous muscle-derived cells
• SUI: Stress urinary incontinence
• FI: Fecal incontinence
• POP: Pelvic organ prolapse
• ECM: Extracellular matrix
• FBR: Foreign body response
• CCM: Concentrated conditioned media
• ERK: Extracellular signal-regulated kinase

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These are the main studies and reviews cited in the review. For full reference list and details, consult the original article.

• Wu JM, et al. Prevalence and trends of symptomatic pelvic floor disorders in US women. Obstet Gynecol. 2014;123(1):141–148. DOI:10.1097/AOG.0000000000000057.

• Le Blanc K, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–1586. DOI:10.1016/S0140-6736(08)60690-X.

• Pittenger MF, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–147. DOI:10.1126/science.284.5411.143.

• Panes J, et al. Expanded allogeneic adipose-derived MSCs (Cx601) for complex perianal fistulas in Crohn’s disease: phase 3. Lancet. 2016;388:1281–1290. DOI:10.1016/S0140-6736(16)31203-X.

• Ranganath SH, et al. Harnessing the MSC secretome for cardiovascular disease. Cell Stem Cell. 2012;10:244–58. DOI:10.1016/j.stem.2012.02.005.

• Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6:1445–1451. DOI:10.1002/sctm.17-0051.

• Lin G, et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2010;12:88–95. DOI:10.3109/14653240903350265.

• Gotoh M, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes. Int J Urol. 2014;21:294–300. DOI:10.1111/iju.12266.

• Ben Menachem-Zidon O, et al. Systemically transplanted MSCs induce vascular-like structure formation in a rat vaginal injury model. PLoS ONE. 2019;14:e0218081. DOI:10.1371/journal.pone.0218081.

• Dissaranan C, et al. Rat MSC secretome promotes elastogenesis and recovery from simulated childbirth injury. Cell Transplant. 2014;23:1395–1406. DOI:10.3727/096368913X670921.

• Liu X, et al. Exosomes from adipose-derived MSCs regulate type I collagen metabolism in fibroblasts from women with SUI. Stem Cell Res Ther. 2018;9:159. DOI:10.1186/s13287-018-0899-9.

• Sun DZ, et al. Harnessing the mesenchymal stem cell secretome for regenerative urology. Nat Rev Urol. 2019;16:363–375. DOI:10.1038/s41585-019-0169-3.

• Ni J, et al. Therapeutic potential of human ADSC exosomes in SUI—an in vitro and in vivo study. Cell Physiol Biochem. 2018;48:1710–1722. DOI:10.1159/000492298.

• Wu R, et al. Exosomes from urine-derived stem cells improve SUI by repairing pubococcygeus muscle in rats. Stem Cell Res Ther. 2019;10:80. DOI:10.1186/s13287-019-1182-4.

• Kuismanen K, et al. Autologous adipose stem cells in treatment of female SUI: pilot study. Stem Cells Transl Med. 2014;3:936–941. DOI:10.5966/sctm.2013-0197.

• Jankowski RJ, et al. Double-blind RCT evaluating autologous muscle-derived cells in female SUI. Int Urol Nephrol. 2018;50:2153–2165. DOI:10.1007/s11255-018-2005-8.

• Burdzinska A, et al. Limited accuracy of transurethral and periurethral intrasphincteric injections. Neurourol Urodyn. 2018;37:1612–1622. DOI:10.1002/nau.23522.

(For the full set of 100+ references used in the original review, please see the original article: Sima Y., Chen Y., Cell Bioscience, 2020. DOI: 10.1186/s13578-020-00466-4.)

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If you would like, I can:

• Extract and format the full original reference list for clinical/regulatory review,
• Summarize individual clinical trials in a table (sample size, cell type, delivery method, outcomes),
• Provide practical guidance on which MSC sources are most relevant for banking and what processing/quality measures to prioritize.