Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic
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ABSTRACT:
SUBMITTER: Huang C
PROVIDER: S-EPMC10683254 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA.
| S-EPMC8640059 | biostudies-literature
Project description:The proteomics of human placenta-derived exosome.
2022-06-12 | PXD034486 |
Project description:BackgroundOsteoarthritis is a leading cause of disability, and disease-modifying osteoarthritis drugs (DMOADs) could represent a pivotal advancement in treatment. Identifying the potential of antidiabetic medications as DMOADs could impact patient care significantly.MethodsWe designed a comprehensive analysis pipeline involving two-sample Mendelian Randomization (MR) (genetic proxies for antidiabetic drug targets), summary-based MR (SMR) (for mRNA), and colocalisation (for drug-target genes) to assess their causal relationship with 12 osteoarthritis phenotypes. Summary statistics from the largest genome-wide association meta-analysis (GWAS) of osteoarthritis and gene expression data from the eQTLGen consortium were utilised.FindingsSeven out of eight major types of clinical antidiabetic medications were identified, resulting in fourteen potential drug targets. Sulfonylurea targets ABCC8/KCNJ11 were associated with increased osteoarthritis risk at any site (odds ratio (OR): 2.07, 95% confidence interval (CI): 1.50-2.84, P < 3 × 10-4), while PPARG, influenced by thiazolidinediones (TZDs), was associated with decreased risk of hand (OR: 0.61, 95% CI: 0.48-0.76, P < 3 × 10-4), finger (OR: 0.50, 95% CI: 0.35-0.73, P < 3 × 10-4), and thumb (OR: 0.49, 95% CI: 0.34-0.71, P < 3 × 10-4) osteoarthritis. Metformin and GLP1-RA, targeting GPD1 and GLP1R respectively, were associated with reduced risk of knee and finger osteoarthritis. In the SMR analyses, gene expression of KCNJ11, GANAB, ABCA1, and GSTP1, targeted by antidiabetic drugs, was significantly linked to at least one osteoarthritis phenotype and was replicated across at least two gene expression datasets. Additionally, increased KCNJ11 expression was related to decreased osteoarthritis risk and co-localised with at least one osteoarthritis phenotype.InterpretationOur findings suggest a potential therapeutic role for antidiabetic drugs in treating osteoarthritis. The results indicate that certain antidiabetic drug targets may modify disease progression, with implications for developing targeted DMOADs.FundingThis study was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (2022), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (Grant No. 20224Y0139), Beijing Natural Science Foundation (Grant No. 7244458), and the Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation (Grant No. GZC20230130).
| S-EPMC11378937 | biostudies-literature
Project description:We describe human chorionic mesenchymal stem cell (hCMSC) lines obtained from the chorion of human term placenta with high therapeutic potential in human organ pathology. hCMSCs propagated for more than 100 doublings without a decrease in telomere length and with no telomerase activity. Cells were highly positive for the embryonic stem cell markers OCT-4, NANOG, SSEA-3, and TRA-1-60. In vitro, cells could be differentiated into neuron-like cells (ectoderm), adipocytes, osteoblasts, endothelial-like cells (mesoderm), and hepatocytes (endoderm)-derivatives of all three germ layers. hCMSCs effectively facilitated repair of injured epithelium as demonstrated in an ex vivo-perfused human lung preparation injured by Escherichia coli endotoxin and in in vitro human lung epithelial cultures. We conclude that the chorion of human term placenta is an abundant source of multipotent stem cells that are promising candidates for cell-based therapies.
| S-EPMC3635148 | biostudies-literature
Project description:Osteoarthritis (OA) is a degenerative joint disease marked by cartilage degradation and loss of function. Recently, there have been increased efforts to attenuate and reverse OA by stimulating cartilage regeneration and preventing cartilage degradation. Human placental extract (HPE) may be an option due to its anti-inflammatory, antioxidant, and growth stimulatory properties. These properties are useful in preventing cell death and senescence, which may optimize in-situ cartilage regeneration. In this review, we discuss the anatomy and physiology of the placenta, as well as explore in vivo and in vitro studies assessing its effects on tissue regeneration. Finally, we assess the potential role of HPE in cartilage regenerative medicine and OA. The Medline database was utilized for all studies that involved the use of HPE or human placenta hydrolysate. Exclusion criteria included articles not written in English, conference reviews, editorials, letters to the editor, surveys, case reports, and case series. HPE had significant anti-inflammatory and regenerative properties in vitro and in vivo. Furthermore, HPE had a role in attenuating cellular senescence and cell apoptosis via reduction of reactive oxidative species both in vitro and in vivo. One study explored the effects of HPE in OA and demonstrated reduction in cartilage catabolic gene expression, indicating HPE’s effect in attenuating OA. HPE houses favorable properties that can attenuate and reverse tissue damage. This may be a beneficial therapeutic in OA as it creates a more favorable environment for in-situ cartilage regeneration. More well designed in-vitro and in-vivo studies are needed to define the role of HPE in treating OA.
| S-EPMC10316113 | biostudies-literature
Project description: Not available
| S-EPMC8323704 | biostudies-literature
Project description:BackgroundStudies in which mesenchymal stromal cells (MSC) from the placenta are compared with multiple MSC types from other sources are rare. The chorionic plate of the human placenta is mainly composed of fetal blood vessels embedded in fetal stroma tissue, lined by trophoblastic cells and organized into chorionic villi (CV) structures.MethodsWe comprehensively characterized human MSC collected from postnatal human chorionic villi of placenta (CV-MSC) by analyzing their growth and proliferation potential, differentiation, immunophenotype, extracellular matrix production, telomere length, aging phenotype, and plasticity.ResultsImmunophenotypic characterization of CV-MSC confirmed the typical MSC marker expression as defined by the International Society for Cellular Therapy. The surface marker profile was consistent with increased potential for proliferation, vascular localization, and early myogenic marker expression. CV-MSC retained multilineage differentiation potential and extracellular matrix remodeling properties. They have undergone reduced telomere loss and delayed onset of cellular senescence as they aged in vitro compared to three other MSC sources. We present evidence that increased human telomerase reverse transcriptase gene expression could not explain the exceptional telomere maintenance and senescence onset delay in cultured CV-MSC. Our in-vitro tumorigenesis detection assay suggests that CV-MSC are not prone to undergo malignant transformation during long-term in-vitro culture. Besides SOX2 expression, no other pluripotency features were observed in early and late passages of CV-MSC.ConclusionsOur work brings forward two remarkable characteristics of CV-MSC, the first being their extended life span as a result of delayed replicative senescence and the second being a delayed aged phenotype characterized by improved telomere length maintenance. MSC from human placenta are very attractive candidates for stem cell-based therapy applications.
| S-EPMC5800083 | biostudies-literature
Project description:Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive loss of articular cartilage, remodeling of the subchondral bone, and synovial inflammation. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that controls critical cellular processes such as growth, proliferation, and protein synthesis. Recent studies suggest that mTOR plays a vital role in cartilage growth and development and in altering the articular cartilage homeostasis as well as contributing to the process of cartilage degeneration associated with OA. Both pharmacological inhibition and genetic deletion of mTOR have been shown to reduce the severity of OA in preclinical mouse models. In this review article, we discuss the roles of mTOR in cartilage development, in maintaining articular cartilage homeostasis, and its potential as an OA therapeutic target.
| S-EPMC4359178 | biostudies-other
Project description:Osteoarthritis (OA) is a prevalent and severely debilitating disease with an unmet medical need. In order to alleviate OA symptoms or prevent structural progression of OA, new drugs, particularly disease-modifying osteoarthritis drugs (DMOADs), are required. Several drugs have been reported to attenuate cartilage loss or reduce subchondral bone lesions in OA and thus potentially be DMOADs. Most biologics (including interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibitors), sprifermin, and bisphosphonates failed to yield satisfactory results when treating OA. OA clinical heterogeneity is one of the primary reasons for the failure of these clinical trials, which can require different therapeutic approaches based on different phenotypes. This review describes the latest insights into the development of DMOADs. We summarize in this review the efficacy and safety profiles of various DMOADs targeting cartilage, synovitis, and subchondral bone endotypes in phase 2 and 3 clinical trials. To conclude, we summarize the reasons for clinical trial failures in OA and suggest possible solutions.
| S-EPMC10184265 | biostudies-literature
Project description:Contemporary treatments for osteoarthritis (OA) pursue only to alleviate the pain caused by the illness. Discovering disease-modifying osteoarthritis drugs (DMOADs) that can induce the repair and regeneration of articular tissues would be of substantial usefulness. The purpose of this manuscript is to review the contemporary role of DMOADs in managing OA. A narrative literature review on the subject, exploring the Cochrane Library and PubMed (MEDLINE) was performed. It was encountered that many publications have analyzed the impact of several DMOAD methods, including anti-cytokine therapy (tanezumab, AMG 108, adalimumab, etanercept, anakinra), enzyme inhibitors (M6495, doxycycline, cindunistat, PG-116800), growth factors (bone morphogenetic protein-7, sprifermin), gene therapy (micro ribonucleic acids, antisense oligonucleotides), peptides (calcitonin) and others (SM04690, senolitic, transient receptor potential vanilloid 4, neural EGFL-like 1, TPCA-1, tofacitinib, lorecivivint and quercitrin). Tanezumab has been demonstrated to alleviate hip and knee pain in individuals with OA but can cause major adverse events (osteonecrosis of the knee, rapid illness progression, augmented prevalence of total joint arthroplasty of involved joints, particularly when tanezumab is combined with nonsteroidal anti-inflammatory drugs. SM04690 (a Wnt inhibitor) has been demonstrated to be safe and efficacious in alleviating pain and ameliorating function as measured by the Western Ontario and McMaster Universities Arthritis Index. The intraarticular injection of lorecivivint is deemed safe and well tolerated, with no important reported systemic complications. In conclusion, even though DMOADs seem promising, their clinical effectiveness has not yet been demonstrated for managing OA. Until forthcoming studies can proved the medications' capacity to repair and regenerate tissues affected by OA, physicians should keep using treatments that only intend to alleviate pain.
| S-EPMC9903308 | biostudies-literature