The Effect of Umbilical Cord-Derived Mesenchymal Stem Cells and Secretome on Metabolomic Profiles (C-Peptide, Adiponectin, Fasting Insulin, and Fasting Glucose): A Randomized Controlled Trial.

Background

Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder with chronic low-grade inflammation and insulin resistance (IR). Elevated C-peptide, a marker of compensatory hyperinsulinemia and reduced adiponectin, an insulin-sensitizing adipokine, contribute to the metabolic dysregulation observed in PCOS. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) and their secretome have immunomodulatory properties via paracrine and epigenetic mechanisms, yet longitudinal evidence in PCOS is limited.

Methods

This randomized controlled trial (RCT) involved 40 women with PCOS (Rotterdam criteria) who were randomly assigned to four treatment groups: (1) metformin 750 mg/day, (2) UC-MSC infusion (0.3 million cells/kg body weight), (3) secretome (nasal drops, 2 mL), and (4) a combination of UC-MSC (0.3 million cells/kg body weight) and secretome (nasal drops, 2 mL). Parameters measured included fasting glucose, fasting insulin, HOMA-IR, C-peptide, and adiponectin at baseline and at months 1, 3, and 6. Analysis was performed using repeated-measures ANOVA or Friedman test, and ROC curves were used to evaluate the predictive value of biomarkers on therapy response.

Results

All participants completed the 6-months of follow-up. The secretome group demonstrated a significant increase in fasting glucose (month 1: p = 0.013; month 3: p = 0.007; month 6: p = 0.032), as well as an increase in adiponectin in the UC-MSC group (month 6: p = 0.016). The combination of UC-MSC and secretome induced early metabolic modulation, characterized by transient reductions in adiponectin at months 1 and 3 (p = 0.022 and p = 0.013, respectively) and early increases in insulin-related parameters; however, these effects were not sustained at month 6. ROC analysis showed that glucose, insulin, and C-peptide variables had low discriminatory ability (AUC < 0.5), while adiponectin showed a trend of increasing predictive value for improving insulin sensitivity.

Conclusions

Combination therapy with UC-MSCs and secretome may have potential to improve metabolic profiles through increasing adiponectin and improving insulin sensitivity in PCOS patients, especially in the group with insulin resistance. MSC-based approaches are not only symptomatic but also have the potential to restore ovarian function through immunomodulatory and epigenetic mechanisms.