{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T20:38:00Z","timestamp":1783802280543,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT Prodia StemCell Indonesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine\u2013metabolic 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/jcm15051707","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:19:23Z","timestamp":1771935563000},"page":"1707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.3390","volume":"15","author":[{"given":"Gunawan Dwi","family":"Prayitno","sequence":"first","affiliation":[{"name":"Doctoral Program of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Gatot Soebroto Army Central Hospital, Central Jakarta City 10410, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Retna","family":"Sartika","sequence":"additional","affiliation":[{"name":"PT Prodia StemCell Indonesia, DKI Jakarta, Central Jakarta City 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-6371","authenticated-orcid":false,"given":"Tono","family":"Djuwantono","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3986-6285","authenticated-orcid":false,"given":"Andi","family":"Wijaya","sequence":"additional","affiliation":[{"name":"PT Prodia StemCell Indonesia, DKI Jakarta, Central Jakarta City 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-3931","authenticated-orcid":false,"given":"Raden","family":"Muharam","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Depok 16424, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8010-5907","authenticated-orcid":false,"given":"Yudi Mulyana","family":"Hidayat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-7078","authenticated-orcid":false,"given":"Rima","family":"Haifa","sequence":"additional","affiliation":[{"name":"PT Prodia StemCell Indonesia, DKI Jakarta, Central Jakarta City 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annisah","family":"Zahrah","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Depok 16424, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Lestari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1210\/jc.2006-0178","article-title":"Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline","volume":"91","author":"Azziz","year":"2006","journal-title":"J. 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