The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Июль 26, 2024

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including self-renewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into clinic has frequently met with inconsistent outcomes. One suspected reasons this issue is inherent extensive variability that exists among such ATMPs, which makes interpretation efficacy difficult assess, as well compare results various studies. This stems from differences in tissue sources, donor attributes, variances manufacturing protocols, modes administration. MSCs can be isolated tissues bone marrow, umbilical cord, adipose others, each its phenotypic functional characteristics. While different sources do share common features, they also exhibit distinct gene expression profiles properites. Donor-specific factors age, sex, body mass index, underlying health conditions influence MSC phenotype, morphology, differentiation function. Moreover, variations preparation products introduces additional heterogeneity result cell culture media composition, presence or absence added growth factors, use serum supplements culturing techniques. Once are formulated, storage protocols play pivotal role efficacy. Factors affect viability include concentration, delivery solution importantly, post-thawing where applicable. Ensuing, administration critically distribution functionallity administered cells. As therapies continue advance through trials, implication strategies reduce product imperative. Central addressing these challenges need precise prediction responses, require well-defined populations harmonized assessment specific functions. By issues by meaningful approaches, as, e.g., pooling, field overcome barriers towards more consistent effective therapies.

Язык: Английский

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Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 3, 2024

Bioactives significantly modify and maintain human health. Available data suggest that might play a beneficial role in chronic inflammatory diseases. Although promised, defining their mechanisms opting to weigh benefits limitations is imperative. Detailed by which critical Bioactives, including probiotics prebiotics such as dietary lipids (DHA, EPA, alpha LA), vitamin D, polysaccharides (fructooligosaccharide), polyphenols (curcumin, resveratrol, capsaicin) potentially modulate inflammation bone metabolism limited. Certain bioactive impact the gut microbiota, immune system, pain response via gut-immune-bone axis. This narrative review highlights recent update on mechanistic evidence demonstrated reduce osteoarthritis pathophysiology.

Язык: Английский

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Recent development of mitochondrial metabolism and dysfunction in osteoarthritis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, extracellular matrix degradation. Disruptions dynamics, including impaired biogenesis, mitophagy, metabolic shifts from phosphorylation glycolysis, exacerbate damage promoting the production of reactive oxygen species matrix-degrading enzymes such ADAMTS MMPs. This review explores molecular mechanisms underlying OA, emphasizing its role homeostasis inflammation. Furthermore, it highlights emerging therapeutic strategies targeting pathways, antioxidants, mitophagy enhancers, modulators, potential interventions mitigate disease progression, which offer promising avenues for advancing personalized disease-modifying treatments OA.

Язык: Английский

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Functional Nanomaterials for the Treatment of Osteoarthritis

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 6731 - 6756

Опубликована: Июль 1, 2024

Abstract: Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 595 million people worldwide. Nanomaterials possess superior physicochemical properties and can influence pathological processes due to their unique structural features, such as size, surface interface, photoelectromagnetic thermal effects. Unlike traditional OA treatments, which suffer from short half-life, low stability, poor bioavailability, high systemic toxicity, nanotherapeutic strategies for offer longer enhanced targeting, improved reduced toxicity. These advantages effectively address limitations of therapies. This review aims inspire researchers develop multifunctional nanomaterials promote practical application in treatment. Keywords: nanostructures, osteoarthritis, drug delivery systems, nanomedicine, precision medicine

Язык: Английский

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Natural Cartilage-Derived Scaffolds for 3D Mesenchymal Stem Cell Culture: Promoting Chondrogenesis and Modulating Secretome Composition

Pharmacognosy Journal, Год журнала: 2025, Номер 16(6), С. 1365 - 1372

Опубликована: Янв. 1, 2025

Introduction: The regenerative potential of stem cells lies in their secretome, a collection signaling molecules whose composition is shaped by the cellular microenvironment and external stimuli. To enhance cartilage regeneration, 3D culture system using natural scaffold has been developed to create more chondrogenic secretome. This study investigates differentiation mesenchymal (MSCs) cultured decellularized bovine analyzes resulting secretome's composition. Methods: employed randomized time series design examine MSCs differentiation. A control group was standard 2D conditions, while two experimental groups were either medium supplemented with chondrocyte (positive control) or scaffold. hypothesized that would promote chondrogenesis at least as effectively positive control. Key markers evaluated various points. Results: Statistical analysis revealed significant differences marker expression between groups. SOX-9 aggrecan elevated both showed higher RUNX-2 highest Coll-2 later Additionally, growth factor had levels IGF-1 FGF-2 towards end study. Conclusion: enhances produces secretome comparable traditional medium, suggesting its promise for regeneration.

Язык: Английский

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Therapeutic efficacy of intra-articular injection of human adipose-derived mesenchymal stem cells in a sheep model of knee osteoarthritis

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 23, 2025

Abstract Background Mesenchymal stem cells have great potential for repairing articular cartilage and treating knee osteoarthritis (KOA). Nonetheless, little is known about the efficacy of human adipose-derived mesenchymal (haMSCs) KOA in large animal models. Methods This study evaluated therapeutic haMSCs repair a sheep model KOA. were isolated, cultured, characterized. was surgically induced by anterior cruciate ligament transection medial meniscectomy, followed intra-articular injection saline (negative control group) or (haMSC into right joint at 6 9 weeks after surgery. Sheep sacrificed 21 surgery, samples (whole joints, femoral condyles, tibias) collected, processed, analyzed. Changes assessed magnetic resonance imaging, micro-computed tomography, macroscopic analysis, histology, immunohistochemistry. Results caused degeneration condyle Conversely, repaired chondral defects increased thickness cartilage. Conclusions These data suggest that can effectively knee.

Язык: Английский

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Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals

Animals, Год журнала: 2025, Номер 15(4), С. 589 - 589

Опубликована: Фев. 18, 2025

Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers promising avenue for improving treatment outcomes, range of emerging therapies showing potential alleviate symptoms promote health. Among these, hyaluronic acid platelet-rich plasma have been widely used as intra-articular treatments enhance lubrication, reduce inflammation, provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, protein solution represent the next generation regenerative therapies, offering more disease-modifying effects by inhibiting key mediators inflammation. More recently, MSC-derived secretome has emerged an innovative, cell-free approach leverages diverse bioactive factors secreted MSCs support tissue repair modulate This review highlights evidence base behind these non-cellular orthobiologic stifle disease, aiming inform veterinary practitioners owners about available options their efficacy supporting conventional treatments.

Язык: Английский

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Minimally Invasive Therapies for Knee Osteoarthritis

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(9), С. 970 - 970

Опубликована: Сен. 13, 2024

Knee osteoarthritis (KOA) is a musculoskeletal disorder characterized by articular cartilage degeneration and chronic inflammation, affecting one in five people over 40 years old. The purpose of this study was to provide an overview traditional novel minimally invasive treatment options role artificial intelligence (AI) streamline the diagnostic process KOA. This literature review provides insights into mechanisms action, efficacy, complications, technical approaches, recommendations intra-articular injections (corticosteroids, hyaluronic acid, plate rich plasma), genicular artery embolization (GAE), nerve ablation (GNA). Overall, there mixed evidence support efficacy that were covered with varying degrees supported through formal medical societies. While GAE GNA are more therapeutic options, preliminary supports their as potential therapy for patients moderate severe Furthermore, evidentiary use AI assist clinicians diagnosis selection In conclusion, many exciting advancements within space

Язык: Английский

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Advanced therapy with mesenchymal stromal cells for knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials

Journal of Orthopaedic Translation, Год журнала: 2024, Номер 48, С. 176 - 189

Опубликована: Авг. 26, 2024

Advanced cell therapies emerged as promising candidates for treatment of knee articular diseases, but robust evidence regarding their clinical applicability is still lacking.

Язык: Английский

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Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Июнь 24, 2024

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment post-traumatic osteoarthritis (PTOA) is beginning receive attention. This review explores current efficacy interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), mesenchymal stem/stromal cells (MSCs), combating PTOA drawing from a comprehensive both preclinical animal models human clinical studies. suggests why joint loading, such as running, might improve outcomes management conjunction with orthiobiologic administration. Accumulating evidence underscores influence on chondrocyte behavior pivotal role pathogenesis. Dynamic has been identified key factor for optimal articular cartilage (AC) health function, offering potential slow down or even reverse progression. We hypothesize that integrating activation mechanotransduction pathways strategies may hold mitigating preventing development. Specific patterns incorporating exercise physical activity remain be defined, particularly setting following trauma.

Язык: Английский

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