{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:05:34Z","timestamp":1786964734592,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"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>Stem cells for regenerative medicine purposes offer therapeutic benefits, but disadvantages are still ill defined. The benefit of stem cells may be attributed to their secretion of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs), including exosomes. We present a novel cell-free stem cell-derived extract (CCM), formulated from human progenitor endothelial stem cells (hPESCs), characterized for biologically active factors using ELISA, nanoparticle tracking analysis and single particle interferometric reflectance imaging sensing. The effect on fibroblast proliferation and ability to induce stem cell migration was analyzed using Alamar Blue proliferation and Transwell migration assays, respectively. GFs including IGFBP 1, 2, 3, and 6, insulin, growth hormone, PDGF-AA, TGF-\u03b1, TGF-\u03b21, VEGF, and the anti-inflammatory cytokine, IL-1RA were detected. Membrane enclosed particles within exosome size range and expressing exosome tetraspanins CD81 and CD9 were identified. CCM significantly increased cell proliferation and induced stem cell migration. Analysis of CCM revealed presence of GFs, CKs, and EVs, including exosomes. The presence of multiple factors including exosomes within one formulation, the ability to promote cell proliferation and induce stem cell migration may reduce inflammation and pain, and augment tissue repair.<\/jats:p>","DOI":"10.3390\/ijms21249364","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T09:17:58Z","timestamp":1607505478000},"page":"9364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-2755","authenticated-orcid":false,"given":"Ashim","family":"Gupta","sequence":"first","affiliation":[{"name":"General Therapeutics, Cleveland Heights, OH 44118, USA"},{"name":"Future Biologics, Lawrenceville, GA 30043, USA"},{"name":"BioIntegrate, Lawrenceville, GA 30043, USA"},{"name":"South Texas Orthopaedic Research Institute, Laredo, TX 78045, USA"},{"name":"Veterans in Pain, Valencia, CA 91354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Cady","sequence":"additional","affiliation":[{"name":"General Therapeutics, Cleveland Heights, OH 44118, USA"},{"name":"Bohlander Stem Cell Research Laboratory, Department of Biology, Bradley University, Peoria, IL 61625, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Fauser","sequence":"additional","affiliation":[{"name":"Bohlander Stem Cell Research Laboratory, Department of Biology, Bradley University, Peoria, IL 61625, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo C.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Future Biologics, Lawrenceville, GA 30043, USA"},{"name":"South Texas Orthopaedic Research Institute, Laredo, TX 78045, USA"},{"name":"School of Osteopathic Medicine, University of the Incarnate Word, San Antonio, TX 78235, USA"},{"name":"Future Physicians of South Texas, San Antonio, TX 78235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Justin","family":"Mistovich","sequence":"additional","affiliation":[{"name":"General Therapeutics, Cleveland Heights, OH 44118, USA"},{"name":"Department of Orthopaedics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish G. R.","family":"Potty","sequence":"additional","affiliation":[{"name":"General Therapeutics, Cleveland Heights, OH 44118, USA"},{"name":"South Texas Orthopaedic Research Institute, Laredo, TX 78045, USA"},{"name":"School of Osteopathic Medicine, University of the Incarnate Word, San Antonio, TX 78235, USA"},{"name":"Laredo Sports Medicine Clinic, Laredo, TX 78041, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5327-3702","authenticated-orcid":false,"given":"Nicola","family":"Maffulli","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, 84084 Fisciano, Italy"},{"name":"San Giovanni di Dio e Ruggi D\u2019Aragona Hospital \u201cClinica Orthopedica\u201d Department, Hospital of Salerno, 84124 Salerno, Italy"},{"name":"Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Queen Mary University of London, London E1 4DG, UK"},{"name":"School of Pharmacy and Bioengineering, Keele University School of Medicine, Stoke on Trent ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.36076\/ppj\/2019.22.s1","article-title":"Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines","volume":"22","author":"Navani","year":"2019","journal-title":"Pain Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1177\/0363546519836090","article-title":"A Practical Guide for the Current Use of Biologic Therapies in Sports Medicine","volume":"48","author":"Lamplot","year":"2020","journal-title":"Am. 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