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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797545317321670656 |
---|---|
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. |
first_indexed | 2024-03-10T14:13:42Z |
format | Article |
id | doaj.art-72b7828e49504596a6308ff85ecad11d |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T14:13:42Z |
publishDate | 2020-12-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT ashimgupta cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT craigcady cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT annemariefauser cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT hugocrodriguez cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT rjustinmistovich cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT anishgrpotty cellfreestemcellderivedextractformulationforregenerativemedicineapplications AT nicolamaffulli cellfreestemcellderivedextractformulationforregenerativemedicineapplications |