Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications

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-fr...

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Main Authors: Ashim Gupta, Craig Cady, Anne-Marie Fauser, Hugo C. Rodriguez, R. Justin Mistovich, Anish G. R. Potty, Nicola Maffulli
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/24/9364
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author Ashim Gupta
Craig Cady
Anne-Marie Fauser
Hugo C. Rodriguez
R. Justin Mistovich
Anish G. R. Potty
Nicola Maffulli
author_facet Ashim Gupta
Craig Cady
Anne-Marie Fauser
Hugo C. Rodriguez
R. Justin Mistovich
Anish G. R. Potty
Nicola Maffulli
author_sort Ashim Gupta
collection DOAJ
description 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-α, TGF-β1, 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.
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spelling doaj.art-72b7828e49504596a6308ff85ecad11d2023-11-20T23:57:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124936410.3390/ijms21249364Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine ApplicationsAshim Gupta0Craig Cady1Anne-Marie Fauser2Hugo C. Rodriguez3R. Justin Mistovich4Anish G. R. Potty5Nicola Maffulli6General Therapeutics, Cleveland Heights, OH 44118, USAGeneral Therapeutics, Cleveland Heights, OH 44118, USABohlander Stem Cell Research Laboratory, Department of Biology, Bradley University, Peoria, IL 61625, USAFuture Biologics, Lawrenceville, GA 30043, USAGeneral Therapeutics, Cleveland Heights, OH 44118, USAGeneral Therapeutics, Cleveland Heights, OH 44118, USADepartment of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, 84084 Fisciano, ItalyStem 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-α, TGF-β1, 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.https://www.mdpi.com/1422-0067/21/24/9364regenerative medicinemusculoskeletal injuriesosteoarthritisstem cellsprogenitor cellsgrowth factors
spellingShingle Ashim Gupta
Craig Cady
Anne-Marie Fauser
Hugo C. Rodriguez
R. Justin Mistovich
Anish G. R. Potty
Nicola Maffulli
Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
International Journal of Molecular Sciences
regenerative medicine
musculoskeletal injuries
osteoarthritis
stem cells
progenitor cells
growth factors
title Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
title_full Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
title_fullStr Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
title_full_unstemmed Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
title_short Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications
title_sort cell free stem cell derived extract formulation for regenerative medicine applications
topic regenerative medicine
musculoskeletal injuries
osteoarthritis
stem cells
progenitor cells
growth factors
url https://www.mdpi.com/1422-0067/21/24/9364
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