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The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also ma...

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Autores principales: Shah, Shiv, Esdaille, Caldon Jayson, Bhattacharjee, Maumita, Kan, Ho-Man, Laurencin, Cato T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764679/
https://www.ncbi.nlm.nih.gov/pubmed/34987101
http://dx.doi.org/10.1073/pnas.2116865118
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author Shah, Shiv
Esdaille, Caldon Jayson
Bhattacharjee, Maumita
Kan, Ho-Man
Laurencin, Cato T.
author_facet Shah, Shiv
Esdaille, Caldon Jayson
Bhattacharjee, Maumita
Kan, Ho-Man
Laurencin, Cato T.
author_sort Shah, Shiv
collection PubMed
description Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.
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spelling pubmed-87646792022-01-26 The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering Shah, Shiv Esdaille, Caldon Jayson Bhattacharjee, Maumita Kan, Ho-Man Laurencin, Cato T. Proc Natl Acad Sci U S A Physical Sciences Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications. National Academy of Sciences 2022-01-05 2022-01-11 /pmc/articles/PMC8764679/ /pubmed/34987101 http://dx.doi.org/10.1073/pnas.2116865118 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Shah, Shiv
Esdaille, Caldon Jayson
Bhattacharjee, Maumita
Kan, Ho-Man
Laurencin, Cato T.
The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title_full The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title_fullStr The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title_full_unstemmed The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title_short The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering
title_sort synthetic artificial stem cell (sasc): shifting the paradigm of cell therapy in regenerative engineering
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764679/
https://www.ncbi.nlm.nih.gov/pubmed/34987101
http://dx.doi.org/10.1073/pnas.2116865118
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