{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:11:08Z","timestamp":1760764268367,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wharton\u2019s jelly-derived mesenchymal stem cells (WJ-MSCs) secrete a rich array of paracrine factors including growth factors, cytokines, and extracellular vesicles that hold promises for regenerative medicine. This study evaluated the effects of WJ-MSC-derived secretome on adipose-derived mesenchymal stem cells (AD-MSCs) and human dermal fibroblasts (HDFs), focusing on their adhesion, spreading, proliferation, endogenous collagen secretion, and migration. Morphometric analysis revealed that the secretome enhanced cell adhesion and spreading on rat tail collagen (RTC) substrates after 24 h. AD-MSCs showed a ~30% increase in the cell spreading area (from 4007 \u03bcm2 to 5081 \u03bcm2p &lt; 0.05), though without notable shape changes. In contrast, fetal bovine serum (FBS) promoted cell elongation with a reduced aspect ratio. Proliferation assays demonstrated a selective stimulatory effect of the secretome on AD-MSCs with a significant increase at day 3, while HDFs\u2019 proliferation remained unchanged. Cell cycle profiling showed transient S-phase accumulation in AD-MSCs (24\u201348 h), followed by G0\/G1 arrest (72 h), while HDFs remained in G0\/G1. Immunofluorescence analysis confirmed the enhanced extracellular deposition of endogenously synthesized collagen in AD-MSCs, while no comparable response was observed in HDFs. Scratch assays showed increased migration in both cell types upon secretome exposure compared to collagen-only controls, suggesting a paracrine-mediated pro-migratory effect. These results demonstrate that WJ-MSC secretome boosts the regenerative capacity in AD-MSCs while keeping fibroblasts quiescent, highlighting its strong potential for cell-free therapies in tissue engineering, wound repair, and regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms262010095","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"10095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective Paracrine Modulation of Stromal Cells: Wharton\u2019s Jelly MSC Secretome Enhances Adipose-Derived MSC Functionality While Maintaining Dermal Fibroblast Quiescence"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6880-4174","authenticated-orcid":false,"given":"Tanya","family":"Stoyanova","sequence":"first","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"Center of Competence in Personalized Medicine, 3D and Telemedicine, Robotic Assisted and Minimally Invasive Surgery\u2014\u201cLeonardo da Vinci\u201d, 5800 Pleven, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7279-4348","authenticated-orcid":false,"given":"Lora","family":"Topalova","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"Center of Competence in Personalized Medicine, 3D and Telemedicine, Robotic Assisted and Minimally Invasive Surgery\u2014\u201cLeonardo da Vinci\u201d, 5800 Pleven, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanimir","family":"Kyurkchiev","sequence":"additional","affiliation":[{"name":"Tissue Bank BulGen, 1330 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1349-9555","authenticated-orcid":false,"given":"Regina","family":"Komsa-Penkova","sequence":"additional","affiliation":[{"name":"Center of Competence in Personalized Medicine, 3D and Telemedicine, Robotic Assisted and Minimally Invasive Surgery\u2014\u201cLeonardo da Vinci\u201d, 5800 Pleven, Bulgaria"},{"name":"Department of Biochemistry, Medical University-Pleven, 5800 Pleven, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-051X","authenticated-orcid":false,"given":"Svetla","family":"Todinova","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Altankov","sequence":"additional","affiliation":[{"name":"Center of Competence in Personalized Medicine, 3D and Telemedicine, Robotic Assisted and Minimally Invasive Surgery\u2014\u201cLeonardo da Vinci\u201d, 5800 Pleven, Bulgaria"},{"name":"Associate Project BG-RRP-2.004-0003, Medical University Pleven, 5800 Pleven, Bulgaria"},{"name":"Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maldonado, V.V., Patel, N.H., Smith, E.E., Barnes, C.L., Gustafson, M.P., Rao, R.R., and Samsonraj, R.M. 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