{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T22:40:35Z","timestamp":1788043235522,"version":"build-2784847793"},"reference-count":197,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY022408"],"award-info":[{"award-number":["EY022408"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["EY023427"],"award-info":[{"award-number":["EY023427"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the \u201csecretome\u201d. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic\/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile\/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs\u2013secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.<\/jats:p>","DOI":"10.3390\/ijms23010249","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T01:18:15Z","timestamp":1640654295000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-8169","authenticated-orcid":false,"given":"Sally L.","family":"Elshaer","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma H.","family":"Bahram","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo 19648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Rajashekar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6664-8286","authenticated-orcid":false,"given":"Rajashekhar","family":"Gangaraju","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology & Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-1989","authenticated-orcid":false,"given":"Azza B.","family":"El-Remessy","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Doctors Hospital of Augusta, Augusta, GA 30909, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"ref_1","first-page":"393","article-title":"The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells","volume":"3","author":"Friedenstein","year":"1970","journal-title":"Cell Tissue Kinet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/sctm.17-0051","article-title":"Mesenchymal Stem Cells: Time to Change the Name!","volume":"6","author":"Caplan","year":"2017","journal-title":"Stem Cells Transl. 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