Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 23, 2025

Articular cartilage injuries can lead to pain, stiffness, and reduced mobility, may eventually progress osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating are still lacking. Mesenchymal stromal cells (MSCs) known for their differentiation immunomodulatory capabilities, yet challenges such as limited survival post-injection inconsistent therapeutic outcomes hinder clinical application. Recent evidence suggests that the beneficial effects MSCs largely mediated by secreted small extracellular vesicles (sEVs), which have been shown promote tissue repair reduce inflammation. MSC-derived sEVs promise in mitigating degradation chondrocyte apoptosis, positioning them a promising alternative MSC-based OA treatment. This review explores potential limitations regeneration. systematic was conducted following PRISMA guidelines, with comprehensive search Web Science Scopus databases studies published between 2019 2024. A total 223 records were identified, 132 articles assessed eligibility based on general selection criteria. After full-text screening, 60 initially selected, comprising 58 vitro 40 vivo studies. Following further exclusion specific criteria, 33 28 from 47 scientific papers included final qualitative synthesis. Most indicate enhance proliferation, improve matrix composition, matrix-degrading enzymes inflammation, thereby delaying progression. growing body supports use tool preventing progression, most reporting structure function. However, remain optimizing standardizing isolation, dosage, delivery methods Further is necessary elucidate mechanisms underlying sEVs-mediated regeneration facilitate translation into therapies.

Language: Английский

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Pre-treated Mesenchymal Stem Cell-Derived Exosomes: A New Perspective for Accelerating Spinal Cord Injury Repair

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177349 - 177349

Published: Feb. 5, 2025

Spinal cord injury (SCI) is a devastating event for the central nervous system (CNS), often resulting in loss of sensory and motor functions. It profoundly affects both physiological psychological well-being patients, reducing their quality life while also imposing significant economic pressure on families healthcare system. Due to complex pathophysiology SCI, effective treatments promoting recovery remain scarce. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer advantages such as low immunogenicity, good biocompatibility, ability cross blood-spinal barrier (BSCB). In preclinical studies, they have progressively shown efficacy SCI repair functional recovery. However, yield insufficient targeting MSC-Exos limit therapeutic efficacy. Currently, genetic engineering other preprocessing techniques are being employed optimize properties exosomes, thereby enhancing potential. Therefore, this paper provides an overview biogenesis exosomes. summarizes current approaches optimizing exosome performance. Additionally, it details mechanisms through which optimized provide neuroprotection explores potential combined involving hydrogels.

Language: Английский

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A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 30, 2024

Abstract Background Extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADSCs) have shown great therapeutic potential in plastic and reconstructive surgery. However, the limited production functional molecule loading of EVs hinder their clinical translation. Traditional two-dimensional culture hADSCs results stemness loss cellular senescence, which is unfavorable for EVs. Recent advances regenerative medicine advocate use three-dimensional to produce EVs, as it more accurately simulates physiological state. Moreover, successful application tissue engineering relies on targeted delivery within biomaterial scaffolds. Methods Results The spheroids gelatin methacrylate (GelMA) microspheres are utilized cultured corresponding spheroids-EVs microspheres-EVs respectively. demonstrate excellent compared with microspheres-EVs. upregulation eight miRNAs (i.e. hsa-miR-486-5p, hsa-miR-423-5p, hsa-miR-92a-3p, hsa-miR-122-5p, hsa-miR-223-3p, hsa-miR-320a, hsa-miR-126-3p, hsa-miR-25-3p) downregulation hsa-miR-146b-5p show improving fate remaining ear chondrocytes promoting cartilage formation probably through integrated regulatory mechanisms. Additionally, a quick innovative pipeline developed isolating chondrocyte homing peptide-modified (CHP-EVs) dynamic cultures spheroids. CHP-EVs produced by genetically fusing CHP at N-terminus exosomal surface protein LAMP2B. + LAMP2B-transfected were wave motion promote secretion CHP-EVs. A harvesting method used enable time-dependent collection easy set up isolation Compared nontagged penetrate scaffolds specifically deliver chondrocytes. Functionally, major effect cell proliferation, reducing apoptosis enhancing M1 macrophage-infiltrated microenvironment. Conclusions In summary, an obtain This can be customized increase loading, meets requirements regulating Graphical

Language: Английский

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Extracellular Vesicles Delivered by a Nanofiber‐Hydrogel Composite Enhance Healing In Vivo in a Model of Crohn's Disease Perianal Fistula

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract Perianal fistulas represent a common, aggressive, and disabling complication of Crohn's disease (CD). Despite recent drug developments, novel surgical interventions as well multidisciplinary treatment approaches, the outcome is dismal, with >50% therapy failure rates. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) offer potential therapeutic benefits for treating fistulizing CD, due to pro‐regenerative paracrine signals. However, significant obstacle clinical translation EV‐based rapid clearance short half‐life EVs in vivo. Here, an injectable, biodegradable nanofiber‐hydrogel composite (NHC) microgel matrix that serves carrier deliver MSC‐derived rat model CD perianal fistula (PAF) reported. It found EV‐loaded NHC (EV‐NHC) yields best healing when compared other arms. The MRI assessment reveals EV‐NHC reduces inflammation at site promotes tissue healing. enhanced outcomes are contributed by extended local retention sustained release NHC. In addition, effectively regeneration via macrophage polarization neo‐vascularization. This platform provides off‐the‐shelf solution facilitates its translation.

Language: Английский

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Current and emerging therapeutic strategies for perirenal fistula in Crohn’s disease patients

Advances in pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 159 - 182

Published: Jan. 1, 2024

Language: Английский

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