Disease-Associated Signatures Persist in Extracellular Vesicles from Reprogrammed Cells of Osteoarthritis Patients

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 870 - 870

Published: Jan. 21, 2025

Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared primary MSCs, induced pluripotent stem (iPSC)-derived MSCs (MLCs) offer superior scalability and enhanced paracrine activity. The aim of this study was explore the feasibility using autologous MLC-derived sEVs potential therapeutic strategy for OA through analysis their protein cargo. iPSCs from an patient healthy donor were differentiated into MLCs. isolated these MLCs characterized, with particular focus on Both iPSC lines successfully MLCs, which secreted comparable size distributions yields. differentially expressed proteins revealed high abundance associated pathology degradation in compared those persistence OA-associated signatures may limit efficacy. These findings underscore importance carefully evaluating disease-specific profiles regenerative applications.

Language: Английский

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An Injectable Kartogenin-Incorporated Hydrogel Supports Mesenchymal Stem Cells for Cartilage Tissue Engineering

Bioengineering, Journal Year: 2025, Volume and Issue: 12(5), P. 434 - 434

Published: April 22, 2025

Background: Cartilage defects and injuries often lead to osteoarthritis, posing significant challenges for cartilage repair. Traditional treatments have limited efficacy, necessitating innovative therapeutic strategies. This study aimed develop an injectable hydrogel-based tissue engineering construct enhance regeneration by combining mesenchymal stem cells (MSCs) the small molecule drug kartogenin (KGN). Methods: An hydrogel was synthesized crosslinking carboxymethyl chitosan (CMC) with aldehyde-modified cellulose nanocrystals (DACNCs). KGN incorporated into during achieve sustained release. Three hydrogels varying CMC/DACNC molar ratios (MR = 0.11, 0.22, 0.33) were developed characterized their structural, mechanical, biocompatible properties. The optimal ratio further evaluated its ability support MSC viability differentiation in vitro. Additionally, signaling pathways (TGF-β, FOXO, PI3K-AKT) investigated elucidate underlying mechanisms. In vivo efficacy assessed using a rabbit femoral trochlear defect model. Results: higher exhibited increased compressive modulus, reduced swelling rate, superior biocompatibility, effectively promoting Signaling pathway analysis revealed activation of TGF-β, PI3K-AKT pathways, suggesting enhanced chondrogenic potential. experiments demonstrated that KGN-MSC-encapsulated significantly improved Conclusions: hydrogel, combined MSCs, synergistically both vitro vivo. highlights potential this as promising scaffold engineering, offering novel approach injuries.

Language: Английский

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Mesenchymal stem cells and their extracellular vesicles: new therapies for cartilage repair

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 24, 2025

Cartilage is crucial for joints, and its damage can lead to pain functional impairment, causing financial burden patients. Due weak self-repair, cartilage injury control a research focus. naturally with age, but mechanical trauma, lifestyle factors certain genetic abnormalities increase the likelihood of symptomatic disease progression. Current treatments include pharmacological surgical interventions, these lack ability stop progression restore regeneration cartilage. Biological therapies have been evaluated show varying degrees efficacy in long-term. The mesenchymal stem cell (MSC) therapy attracts attention as it easily harvested expanded. Once thought repair via differentiation, MSCs are now known secrete extracellular vesicles (EVs) paracrinely. These EVs, rich bioactive molecules, enable communication, boost growth factor secretion, regulate synthesis degradation matrix (ECM), modulate inflammation, vital repair. However, further clinical validation still required application MSC MSC-EVs. This review highlights current state on use MSC-EVs treatment injury. It hoped that this paper will provide valuable references inspiration future researchers therapeutic studies

Language: Английский

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3D-printed advanced scaffold armed with exosomes derived from human skeletal stem cell identified by single-cell RNA sequencing enhances osteochondral regeneration

Bioactive Materials, Journal Year: 2025, Volume and Issue: 51, P. 231 - 256

Published: May 14, 2025

Language: Английский

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An Injectable Kartogenin-Incorporated Hydrogel Supports Mesenchymal Stem Cells for Cartilage Tissue Engineering

Published: Jan. 1, 2024

Language: Английский

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sEV-mediated Lipid Droplets Transferred from Bone Marrow Adipocytes promote ferroptosis and impair Osteoblast Function

Journal of Lipid Research, Journal Year: 2024, Volume and Issue: unknown, P. 100657 - 100657

Published: Sept. 1, 2024

Language: Английский

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3D printed scaffold based on polycaprolactone/self-assembled fullerene (C60) nanorod for bone tissue engineering

Emergent Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Language: Английский

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