Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Abstract Background The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton’s Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellula...

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Main Authors: Ashim Gupta, Saadiq F. El-Amin, Howard J. Levy, Rebecca Sze-Tu, Sobrasua E. Ibim, Nicola Maffulli
Format: Article
Language:English
Published: BMC 2020-02-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-020-1553-7
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author Ashim Gupta
Saadiq F. El-Amin
Howard J. Levy
Rebecca Sze-Tu
Sobrasua E. Ibim
Nicola Maffulli
author_facet Ashim Gupta
Saadiq F. El-Amin
Howard J. Levy
Rebecca Sze-Tu
Sobrasua E. Ibim
Nicola Maffulli
author_sort Ashim Gupta
collection DOAJ
description Abstract Background The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton’s Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton’s jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. Methods Human umbilical cords were obtained from consenting caesarian section donors. The Wharton’s jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. Results All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. Conclusion There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton’s jelly formulation analyzed. The amount of these factors in Wharton’s jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.
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spelling doaj.art-095dfcce7e754380a269980dcd2972642022-12-22T04:09:24ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2020-02-011511910.1186/s13018-020-1553-7Umbilical cord-derived Wharton’s jelly for regenerative medicine applicationsAshim Gupta0Saadiq F. El-Amin1Howard J. Levy2Rebecca Sze-Tu3Sobrasua E. Ibim4Nicola Maffulli5BioIntegrateBioIntegrateBioIntegrateDepartment of Biomedical Engineering, Columbia UniversityMorris Brown CollegeDepartment of Musculoskeletal Disorders, School of Medicine and Surgery, University of SalernoAbstract Background The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton’s Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton’s jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. Methods Human umbilical cords were obtained from consenting caesarian section donors. The Wharton’s jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. Results All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. Conclusion There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton’s jelly formulation analyzed. The amount of these factors in Wharton’s jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.https://doi.org/10.1186/s13018-020-1553-7Regenerative medicineMusculoskeletal injuriesOsteoarthritisBiologicsUmbilical cordWharton’s jelly
spellingShingle Ashim Gupta
Saadiq F. El-Amin
Howard J. Levy
Rebecca Sze-Tu
Sobrasua E. Ibim
Nicola Maffulli
Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
Journal of Orthopaedic Surgery and Research
Regenerative medicine
Musculoskeletal injuries
Osteoarthritis
Biologics
Umbilical cord
Wharton’s jelly
title Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
title_full Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
title_fullStr Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
title_full_unstemmed Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
title_short Umbilical cord-derived Wharton’s jelly for regenerative medicine applications
title_sort umbilical cord derived wharton s jelly for regenerative medicine applications
topic Regenerative medicine
Musculoskeletal injuries
Osteoarthritis
Biologics
Umbilical cord
Wharton’s jelly
url https://doi.org/10.1186/s13018-020-1553-7
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