Intra Ovarian Muse Cell Injection for Perimenopause Symptom Relief and Ovarian Function Restoration (MUSE-OVARY)

Background:

Perimenopause involves progressive ovarian follicular depletion, erratic hypothalamic pituitary ovarian (HPO) axis function, oxidative stress, mitochondrial dysfunction, chronic low grade inflammation, and epigenetic changes. These processes lead to hormonal instability and associated symptoms. While hormone replacement therapy alleviates symptoms, it does not restore endogenous ovarian activity.

Muse cells (Multilineage-differentiating Stress-Enduring cells) are endogenous, non-tumorigenic, pluripotent like mesenchymal stem cells naturally residing in adult bone marrow, adipose tissue, and connective tissues. They demonstrate spontaneous tri-lineage differentiation potential, high stress tolerance, immune-privileged properties, and selective homing to damaged sites without genetic reprogramming or requirement for HLA matching/immunosuppression in many contexts.

Study Design

This prospective, single arm, single center observational cohort study evaluates real world safety, feasibility, and outcomes following ultrasound-guided intra-ovarian Muse cell injection in women aged 28-70 meeting STRAW+10 criteria for perimenopause. Participants self-select the procedure as part of clinical regenerative medicine care at the study site; no randomization or protocol-driven intervention assignment occurs.

Rationale and Mechanisms

Preclinical and analogous mesenchymal stem cell research in premature ovarian insufficiency (POI) and perimenopausal models suggests potential benefits through interconnected pathways, including paracrine/exosomal signaling (VEGF, IGF-1, FGF2, miR-21/miR-132), mitochondrial transfer via tunneling nanotubes, reduction of reactive oxygen species, anti-apoptotic effects (Bcl-2/Akt/survivin), immunomodulation (TGF-β1, IL-10, PGE2; shift toward Treg phenotype and reduced dendritic cell maturation), and epigenetic remodeling (delivery of DNMTs/HATs, reactivation of folliculogenesis-related genes such as FOXL2, GDF9, BMP15). Additional upstream effects on hypothalamic GnRH pulsatility and pituitary responsiveness may support overall HPO axis coordination.

Similar intra-ovarian autologous or allogeneic mesenchymal stem cell approaches in POI/perimenopausal cohorts have reported signals of improved hormonal parameters, antral follicle counts, menstrual regularity, and symptom relief with acceptable shortterm safety profiles.

Intervention Overview (high-level only) Clinical-grade Muse cells (autologous preferred from adipose or bone marrow; or allogeneic where authorized) are prepared under GMP conditions and administered via transvaginal ultrasound-guided bilateral ovarian stromal injection (laparoscopic alternative if indicated), with optional systemic intravenous support. Dosing follows a safety-informed range (0.5-2.0 × 10⁶ cells/kg total, divided between ovaries).

Objectives

Primary: Characterize safety (adverse events per CTCAE v5.0), procedural tolerability, and ovarian morphology changes over 24 months.

Secondary: Document longitudinal changes in hormonal profiles, ultrasound-based follicular parameters, menstrual cyclicity, and patient-reported outcomes (MENQOL).

Exploratory: Assess candidate mechanistic biomarkers (exosomal miRNAs, epigenetic clocks, cytokines, oxidative stress markers).

Follow-up

Standardized evaluations occur at baseline and at 1, 3, 6, 12, and 24 months, with extended annual safety monitoring up to 5 years via a registry. Assessments include serial hormone panels, transvaginal ultrasound, symptom diaries, quality-of-life measures, and safety surveillance. Optional biobanking supports future analyses.

This observational framework enables ethical collection of standardized real-world evidence on an emerging regenerative approach while generating hypothesis generating data to guide subsequent controlled trials. Information already captured elsewhere in the record (e.g., eligibility criteria, outcome measures, study type) is not repeated here.

Inclusion criteria

Women aged 28 to 70 years at the time of enrollment.

Diagnosis of perimenopause according to STRAW+10 criteria, including irregular menstrual cycles (cycle length variation >7 days), elevated FSH (>25 IU/L on two occasions), low AMH (<1.0 ng/mL), and/or presence of perimenopausal symptoms (vasomotor symptoms, sleep disturbance, mood changes, or cognitive complaints).

Willingness to receive ultrasound-guided intra-ovarian Muse cell injection as part of elective clinical regenerative medicine care.

Ability to provide written informed consent and comply with scheduled follow-up visits, blood draws, ultrasounds, and questionnaires for 24 months.

Adequate general health to undergo the procedure under sedation or local anesthesia, as determined by the treating physician.

Exclusion criteria

History of ovarian/gynecologic malignancy (active or <5 years remission). Active autoimmune disease requiring immunosuppression.

Uncontrolled comorbidities (e.g., severe cardiovascular disease, coagulopathy, uncontrolled diabetes or thyroid disease).

Current pregnancy or lactation.

Recent hormone therapy (within 3 months).

BMI >40 kg/m² or other factors increasing procedural risk.

Inability to comply with study procedures.