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

Prospective Single Arm Observational Cohort Study of Ultrasound Guided Intra Ovarian Injection of Muse Cells (Multilineage Differentiating Stress-Enduring Cells) for Reversal of Perimenopausal Ovarian Decline in Women Aged 28-70 Years

This observational study examines the safety and effects of injecting Muse cells (a type of naturally occurring stem like cells found in adult tissues such as fat or bone marrow) directly into the ovaries of women aged 28 to 70 who are going through peri-menopause.

Perimenopause is the transition time before menopause when hormone levels fluctuate, periods become irregular, and many women experience symptoms like hot flashes, night sweats, sleep problems, mood changes, and reduced energy. Current treatments mainly manage symptoms but do not restore natural ovarian function.

Muse cells have special properties: they can help repair tissues, reduce inflammation, support cell energy production, and promote a healthier environment in the ovaries. In this study, women who choose to receive ultrasound guided Muse cell injections into their ovaries as part of their own regenerative care will be carefully followed.

Researchers will monitor safety, hormone levels (such as FSH, estrogen, and AMH), ovarian follicle counts via ultrasound, menstrual patterns, and quality of life improvements using questionnaires. The study does not assign treatment - participants and their doctors decide on the procedure, and information is collected in a standardized way over 24 months (with longer safety follow-up).

The goal is to gather real world data on whether this approach can help stabilize hormones and support ovarian tissue during perimenopause. No placebos or experimental drugs are used in this observational study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Quality of Life; Vasomotor Symptoms; Menopause; Cell Therapy; Hormone Disturbance; Premature Ovarian Failure; Vasomotor Symptoms as a Sex Hormone-dependent Disorder in Women and Men; Diminished Ovarian Reserve; Perimenopause; Vasomotor Symptoms Associated With Menopause; Premature Ovarian Failure (POF); Premature Ovarian Insufficiency; Menopause Ovarian Failure; Quality of Life and Menopause; Vasomotor Symptoms (VMS); Diminished Ovarian Reserve Due to Advanced Maternal Age; Menopause Hot Flashes; Perimenopause-Related Depression; Ovarian Dysfunction; Diminished Ovarian Reserve (DOR); Womens Health; Hormonal Imbalance

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 12

Contacts and Locations

Study Locations

• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • Stem Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a prospective observational cohort study using convenience sampling. Participants are women aged 28-70 experiencing perimenopause who independently elect to receive ultrasound guided intra ovarian Muse cell injection as part of their routine clinical regenerative medicine care at the study center.

No random sampling, probability based recruitment, or protocol-mandated intervention assignment occurs. Enrollment is open to eligible women who present seeking regenerative options for perimenopausal symptoms and ovarian support.

The sampling approach reflects real world clinical practice, allowing collection of standardized longitudinal data on safety and outcomes in a self selected population. Potential selection bias toward motivated individuals interested in regenerative therapies is acknowledged and will be addressed through transparent reporting and subgroup analyses.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

MUSE-OVARY Cohort A; All participants in this single-arm observational cohort are women aged 28-70 years experiencing perimenopause who elect to receive ultrasound-guided intra-ovarian injection of Muse cells (Multilineage-differentiating Stress-Enduring cells) as part of their standard clinical regenerative medicine care. No participants are assigned to any intervention by the study protocol; treatment decisions are made between the participant and their physician. Muse cells are prepared under GMP conditions. Cells are administered via transvaginal ultrasound guided bilateral ovarian stromal injection (or laparoscopic approach if clinically indicated), with an optional concurrent intravenous infusion for systemic support. Participants are followed prospectively with standardized assessments of safety, hormonal parameters, ovarian morphology via ultrasound, menstrual patterns, live births and quality of life measures for 24 months, with extended safety monitoring up to 5 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events and Serious Adverse Events	Safety and tolerability of ultrasound-guided intra-ovarian Muse cell injection, assessed by the incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From baseline through 36 months post procedure, with focused monitoring in the first 30 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FSH Hormonal Profile	Longitudinal changes in serum levels of follicle stimulating hormone (FSH). Measured to evaluate potential stabilization or improvement in endocrine function.	Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post-procedure.
Change in LH Hormonal Profile	Longitudinal changes in serum levels of luteinizing hormone (LH). Measured to evaluate potential stabilization or improvement in endocrine function.	Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post procedure.
Change in AMH Hormonal Profile	Longitudinal changes in serum levels of anti-Müllerian hormone (AMH). Measured to evaluate potential stabilization or improvement in endocrine function.	Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post-procedure.
Change in Estradiol Hormonal Profile	Longitudinal changes in serum levels of estradiol (E2). Measured to evaluate potential stabilization or improvement in endocrine function.	Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post-procedure.
Change in Progesterone Hormonal Profile	Longitudinal changes in serum levels of progesterone. Measured to evaluate potential stabilization or improvement in endocrine function.	Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months post-procedure.
Ovarian Follicular Reserve by Ultrasound	Change in antral follicle count (AFC) and ovarian volume assessed by transvaginal ultrasound, as objective markers of ovarian tissue response and follicular activity.	Baseline, 3 months, 6 months, 12 months, and 24 months post-procedure.
Menstrual Cycle Regularity	Proportion of participants achieving improved menstrual regularity (reduction in cycle variability) or resumption of menses, documented via participant menstrual diaries.	Assessed continuously through 24 months; summarized at 6, 12, and 24 months.
Quality of Life and Symptom Improvement	Change in perimenopausal symptoms and overall quality of life measured by the Menopause Specific Quality of Life Questionnaire (MENQOL). Domains include vasomotor, psychosocial, physical, and sexual functioning. Success defined as ≥50% improvement in total score from baseline.	Baseline, 3 months, 6 months, 12 months, and 24 months post procedure.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy and Live Birth Incidence	Descriptive reporting of spontaneous conceptions, IVF attempts/outcomes, clinical pregnancies, and live births during follow-up, including any associated obstetric/neonatal data where available. Not powered as a formal efficacy endpoint.	Baseline, 1 month, 3 months, 6 months, and 12 months.

Collaborators and Investigators

• Sponsor: Healing Hope International
• Investigators: Principal Investigator: Dr. Jonatha Leicher, MD: Regenerative Medicine, Healing Hope International

Publications and helpful links

General Publications

• Kim HK,Kim TJ
• Alanazi RF,Alhwity BS,Almahlawi RM,Alatawi BD,Albalawi SA,Albalawi RA,Albalawi AA,Abdel-Maksoud MS,Elsherbiny N
• Dezawa M. Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells: Direct Contribution of Muse Cells to Tissue Regeneration. Cell Transplant. 2016;25(5):849-61. doi: 10.3727/096368916X690881. Epub 2016 Feb 15.
• Dezawa M. The Muse Cell Discovery, Thanks to Wine and Science. Adv Exp Med Biol. 2018;1103:1-11. doi: 10.1007/978-4-431-56847-6_1.
• Wakao S, Akashi H, Kushida Y, Dezawa M. Muse cells, newly found non-tumorigenic pluripotent stem cells, reside in human mesenchymal tissues. Pathol Int. 2014 Jan;64(1):1-9. doi: 10.1111/pin.12129.
• Ogura F, Wakao S, Kuroda Y, Tsuchiyama K, Bagheri M, Heneidi S, Chazenbalk G, Aiba S, Dezawa M. Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine. Stem Cells Dev. 2014 Apr 1;23(7):717-28. doi: 10.1089/scd.2013.0473. Epub 2014 Jan 17.
• Tatsumi K, Kushida Y, Wakao S, Kuroda Y, Dezawa M. Protocols for Isolation and Evaluation of Muse Cells. Adv Exp Med Biol. 2018;1103:69-101. doi: 10.1007/978-4-431-56847-6_4.
• Dezawa M. Clinical Trials of Muse Cells. Adv Exp Med Biol. 2018;1103:305-307. doi: 10.1007/978-4-431-56847-6_17.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 30, 2030

Study Registration Dates

• First Submitted: March 28, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Quality of Life; Menopause; Women's Health; Regenerative medicine; Vasomotor Symptoms; Perimenopause; Hot Flashes; Hormone Disturbance; Premature Ovarian Failure; Premature Ovarian Insufficiency; POI; Diminished Ovarian Reserve; Ovarian rejuvenation; Intra-ovarian injection; Hormonal Imbalance; ovarian rejuvenation therapy; menopause hot flashes; Ovarian Dysfunction; MuSE; hormone restoration ovaries; Muse cells perimenopause; intra ovarian injection menopause; perimenopause stem cell; perimenopause related depression; menopause ovarian failure
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Neoplastic Syndromes, Hereditary; Neoplasms, Multiple Primary; Multiple Endocrine Neoplasia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Primary Ovarian Insufficiency; Endocrine System Diseases; Hot Flashes; Multiple Endocrine Neoplasia Type 1
• Other Study ID Numbers: MUSE-OVARY-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data (IPD) may be shared in the future following study completion, subject to appropriate de-identification, ethical approvals, and compliance with applicable regulatory and privacy standards. Data sharing will be considered to support scientific transparency and collaboration while protecting participant confidentiality and respecting international data governance requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No