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Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derive...

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Autores principales: Yin, Zhaowei, Qin, Chaoren, Pan, Shaowei, Shi, Chen, Wu, Guanfu, Feng, Yan, Zhang, Jing, Yu, Ziyi, Liang, Bin, Gui, Jianchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562164/
https://www.ncbi.nlm.nih.gov/pubmed/37822452
http://dx.doi.org/10.1016/j.mtbio.2023.100813
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author Yin, Zhaowei
Qin, Chaoren
Pan, Shaowei
Shi, Chen
Wu, Guanfu
Feng, Yan
Zhang, Jing
Yu, Ziyi
Liang, Bin
Gui, Jianchao
author_facet Yin, Zhaowei
Qin, Chaoren
Pan, Shaowei
Shi, Chen
Wu, Guanfu
Feng, Yan
Zhang, Jing
Yu, Ziyi
Liang, Bin
Gui, Jianchao
author_sort Yin, Zhaowei
collection PubMed
description Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos(IPFP)) and ScAT stem cells (Exos(ScAT)) in OA treatment. Results suggested that Exos(IPFP) significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos(ScAT), following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos(ScAT) (Exos(ScAT−99b−3p)), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos(ScAT) would enable them to exhibit comparable or even superior effectiveness to Exos(IPFP) for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.
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spelling pubmed-105621642023-10-11 Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis Yin, Zhaowei Qin, Chaoren Pan, Shaowei Shi, Chen Wu, Guanfu Feng, Yan Zhang, Jing Yu, Ziyi Liang, Bin Gui, Jianchao Mater Today Bio Full Length Article Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos(IPFP)) and ScAT stem cells (Exos(ScAT)) in OA treatment. Results suggested that Exos(IPFP) significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos(ScAT), following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos(ScAT) (Exos(ScAT−99b−3p)), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos(ScAT) would enable them to exhibit comparable or even superior effectiveness to Exos(IPFP) for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies. Elsevier 2023-09-28 /pmc/articles/PMC10562164/ /pubmed/37822452 http://dx.doi.org/10.1016/j.mtbio.2023.100813 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Yin, Zhaowei
Qin, Chaoren
Pan, Shaowei
Shi, Chen
Wu, Guanfu
Feng, Yan
Zhang, Jing
Yu, Ziyi
Liang, Bin
Gui, Jianchao
Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title_full Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title_fullStr Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title_full_unstemmed Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title_short Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis
title_sort injectable hyperbranched peg crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous adscs-derived exosomes was beneficial for long-term treatment of osteoarthritis
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562164/
https://www.ncbi.nlm.nih.gov/pubmed/37822452
http://dx.doi.org/10.1016/j.mtbio.2023.100813
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