Dataset Information

Comparison of the ability of exosomes and ectosomes derived from mesenchymal stem cells to promote cartilage regeneration in a rat osteochondral defect model

ABSTRACT: Background: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration. Methods: Our study compared the effects of the two EVs on chondrocytes and bone marrow–derived MSCs (BMSCs) in vitro and loaded them into type I collagen hydrogels to optimize EV application for the treatment of osteochondral defects in vivo. Results: In vitro experiments demonstrate that ASC-Exos significantly promoted the proliferation and migration of both cells more effectively than ASC-Ectos. Furthermore, ASC-Exos facilitated a stronger differentiation of BMSCs into chondrogenic cells than ASC-Ectos, but both inhibited chondrocyte apoptosis to a similar extent. In the osteochondral defect model of rats, ASC-Exos promoted cartilage regeneration in situ better than ASC-Ectos. At 8 weeks, the Gel+Exo group had higher macroscopic and histological scores, a higher value of BV/TV, a lower value of Tb.Sp, and a better remodeling of extracellular matrix than the Gel+Ecto group. At 4 and 8 weeks, the expression of CD206 and Arginase-1 in the Gel+Exo group was significantly higher than that in the Gel+Ecto group. Conclusion: Our findings indicate that administering ASC-Exos may be a more effective EV strategy for cartilage regeneration than the administration of ASC-Ectos.

ORGANISM(S): Rattus Rattus

SUBMITTER: Xuesong Dai

PROVIDER: PXD041283 | iProX | Sat Apr 01 00:00:00 BST 2023

REPOSITORIES: iProX

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Publications

Comparison of the ability of exosomes and ectosomes derived from adipose-derived stromal cells to promote cartilage regeneration in a rat osteochondral defect model.

Xu Tengjing T Yu Xinning X Xu Kaiwang K Lin Yunting Y Wang Jiajie J Pan Zongyou Z Fang Jinghua J Wang Siheng S Zhou Zhuxing Z Song Hongyun H Zhu Sunan S Dai Xuesong X

Stem cell research & therapy 20240117 1

<h4>Background</h4>Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration.<h4>Methods</h4>Our study compared the effects of the two EVs isolated from adipose-derived MSCs (ASCs) on chondrocytes a ...[more]

PMID: 38229196

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Project description:Fetal cartilage fully regenerates following injury while in adult mammals cartilage injury leads to osteoarthritis (OA). OA is characterized by cartilage breakdown and joint inflammation and associated with significant pain and socioeconomic costs. As no clinically satisfactory treatment is available to date, disease-modifying therapies aimed to achieve cartilage regeneration are urgently required. The inherent regeneration potential of fetal individuals may hold answers to this unmet need. Therefore, to characterize the differences in fetal and adult response to cartilage injury, we carried out histology and comprehensive proteome analyses on fetal (day 80/150-day gestation) and adult cartilage samples one (fetal samples) and three (adult and fetal samples) days after surgical induction of a full-thickness cartilage lesion. In addition, proteins secreted by inflamed fetal MSCs in vitro were compared with the in vivo response to injury to evaluate their therapeutic potential. Histology of synovial samples revealed the presence of neutrophils one day post injury (p.i.) and an influx of macrophages into the subsynovial tissue on day 3 p.i. in fetal samples. In contrast, adult synovial samples showed invasion of neutrophils on day 3 p.i. Activation and migration of Iba1+- macrophages of the synovial lining was observed both in fetal and adult animals. Comparative mass spectrometry revealed 57 proteins significantly up-regulated (> 2FC, FDR<0.05), and 67 proteins significantly down-regulated (<-2 FC) upon injury in adults. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult cartilage following injury compared to fetal sheep. In contrast, several immunomodulating proteins and growth factors were significantly higher expressed in the fetus than the adult. Comparison of the in vitro MSCs with the in vivo fetal proteome revealed shared upregulation of 17 proteins, which were considered to be of potential therapeutic interest. The results of this study support our molecular understanding of successful fetal cartilage healing and new therapeutic strategies to induce regeneration in adult articular cartilage by modulating the inflammatory environment. The shared protein upregulation in fetal cartilage in vivo and in fetal MSCS during in vitro inflammation supports the possible therapeutic potential of these factors in specific and fetal MSCs in general.

Dataset Information

Comparison of the ability of exosomes and ectosomes derived from mesenchymal stem cells to promote cartilage regeneration in a rat osteochondral defect model

Publications

Comparison of the ability of exosomes and ectosomes derived from adipose-derived stromal cells to promote cartilage regeneration in a rat osteochondral defect model.

Similar Datasets

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