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A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome

BACKGROUND: Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet req...

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Autores principales: Shoma Suresh, K., Bhat, Samatha, Guru, Bharath Raja, Muttigi, Manjunatha S., Seetharam, Raviraja N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251860/
https://www.ncbi.nlm.nih.gov/pubmed/32460846
http://dx.doi.org/10.1186/s13287-020-01712-9
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author Shoma Suresh, K.
Bhat, Samatha
Guru, Bharath Raja
Muttigi, Manjunatha S.
Seetharam, Raviraja N.
author_facet Shoma Suresh, K.
Bhat, Samatha
Guru, Bharath Raja
Muttigi, Manjunatha S.
Seetharam, Raviraja N.
author_sort Shoma Suresh, K.
collection PubMed
description BACKGROUND: Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet requirement for clinical translation. METHODS: We developed a nanocomposite-hydrogel (NP-H) comprised of poly-L-lactide nanoparticles (NPs) embedded in gelatin/hyaluronic acid (Gel/HA) hydrogel as a delivery vehicle for MSC-CM. First, we optimized the culture conditions for bone marrow-derived MSCs using serum-containing medium (SCM) and serum-free medium (SFM) and characterized the corresponding CM (serum-containing conditioned medium (ScCM) and serum-free conditioned medium (SfCM), respectively) for its potency and xeno markers. Then we prepared a composite matrix followed by physiochemical characterization and functional assays were performed. RESULTS: Nanocomposite hydrogel displayed an even distribution of NPs along with high porosity (> 60%) and swelling ratios > 1500%, while its protein release pattern corresponded to a mix of degradation and diffusion kinetics. Functional evaluation of the composites was determined using MSCs and human fibroblasts (HFFs). The cells seeded directly onto the composites displayed increasing metabolic activities over time, with ScCM-NP-H groups having maximum activity. The cells treated in vitro with 5% and 10% extracts of ScCM-NP-H and SfCM-NP-H exhibited a dose- and duration-dependent response. Cell activities reduced considerably for all groups, except 10% ScCM-NP-H, which displayed a significant increase over time. CONCLUSION: We observed that sustained release of MSC-CM is required to prevent dose-dependent cytotoxicity. The proposed nanocomposite hydrogel for MSC-CM delivery can open up a new array for its clinical application.
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spelling pubmed-72518602020-06-07 A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome Shoma Suresh, K. Bhat, Samatha Guru, Bharath Raja Muttigi, Manjunatha S. Seetharam, Raviraja N. Stem Cell Res Ther Research BACKGROUND: Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet requirement for clinical translation. METHODS: We developed a nanocomposite-hydrogel (NP-H) comprised of poly-L-lactide nanoparticles (NPs) embedded in gelatin/hyaluronic acid (Gel/HA) hydrogel as a delivery vehicle for MSC-CM. First, we optimized the culture conditions for bone marrow-derived MSCs using serum-containing medium (SCM) and serum-free medium (SFM) and characterized the corresponding CM (serum-containing conditioned medium (ScCM) and serum-free conditioned medium (SfCM), respectively) for its potency and xeno markers. Then we prepared a composite matrix followed by physiochemical characterization and functional assays were performed. RESULTS: Nanocomposite hydrogel displayed an even distribution of NPs along with high porosity (> 60%) and swelling ratios > 1500%, while its protein release pattern corresponded to a mix of degradation and diffusion kinetics. Functional evaluation of the composites was determined using MSCs and human fibroblasts (HFFs). The cells seeded directly onto the composites displayed increasing metabolic activities over time, with ScCM-NP-H groups having maximum activity. The cells treated in vitro with 5% and 10% extracts of ScCM-NP-H and SfCM-NP-H exhibited a dose- and duration-dependent response. Cell activities reduced considerably for all groups, except 10% ScCM-NP-H, which displayed a significant increase over time. CONCLUSION: We observed that sustained release of MSC-CM is required to prevent dose-dependent cytotoxicity. The proposed nanocomposite hydrogel for MSC-CM delivery can open up a new array for its clinical application. BioMed Central 2020-05-27 /pmc/articles/PMC7251860/ /pubmed/32460846 http://dx.doi.org/10.1186/s13287-020-01712-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shoma Suresh, K.
Bhat, Samatha
Guru, Bharath Raja
Muttigi, Manjunatha S.
Seetharam, Raviraja N.
A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title_full A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title_fullStr A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title_full_unstemmed A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title_short A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
title_sort nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251860/
https://www.ncbi.nlm.nih.gov/pubmed/32460846
http://dx.doi.org/10.1186/s13287-020-01712-9
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