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Preclinical study on safety and efficacy of GMP human umbilical cord mesenchymal stem cells in knee osteoarthritis

ABSTRACT: Preclinical study on safety and efficacy of GMP human umbilical cord mesenchymal stem cells in knee osteoarthritis

PROVIDER: PRJNA1054550 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27285267.fastq.gz	Fastqsanger.gz
	SRR27285268.fastq.gz	Fastqsanger.gz
	SRR27285269_1.fastq.gz	Fastqsanger.gz
	SRR27285269_2.fastq.gz	Fastqsanger.gz
	SRR27285270_1.fastq.gz	Fastqsanger.gz

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Preclinical study on safety and efficacy of GMP human umbilical cord mesenchymal stem cells in knee osteoarthritis

Project description:Clinical trials of MSCs in the treatment of OA have been carried out and good results have been obtained. However, these data on the dose of transplanted cells, the number of transplants, the therapeutic effect especially cartilage regeneration and safety are incomplete. Therefore, we constructed a cynomolgus macaque model consistent with the pathogenesis of OA. We have also established clinical-grade human umbilical cord-derived mesenchymal stem cell line. We selected two cell doses (2.5*10e7 cells per knee and 5*10e6 cells per knee, respectively) to assess differences in treatment effects and to assess the systemic safety of MSC therapy. High-dose hUC-MSCs can regenerate cartilage, increase joint space, and improve bone condition by ultrasound and MRI scans. But low-dose hUC-MSCs simply prevented further deterioration of the joint

2024-05-01 | GSE250569 | GEO

PRODUCT CHARACTERIZATION AND PRECLINICAL SAFETY OF UMBILICAL CORD MESENCHYMAL STROMAL CELL-DERIVED SMALL EXTRACELLULAR VESICLES

Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors that can be isolated from different sources, such as the bone marrow, adipose tissue and umbilical cord. The therapeutic potential of MSCs is related to a plethora of immunomodulatory, anti-inflammatory and pro-repair actions, which are at least partially dependent on their secretome. Among the components of MSCs' secretome, EVs have received considerable attention because MSC-EVs exert similar therapeutic properties as their parent cells. Among the different MSC sources for EV production, human umbilical cord MSCs (hUCMSCs) show advantages such as tissue availability, high proliferative profile of the cells and potential beneficial therapeutic effects in a variety of different diseases, such as stroke This study aimed to provide novel insights for future hUCMSC-EVs research and treatment selection. We investigated the influence of the culture and harvesting conditions on the EV proteomic profile, productivity, surface markers expression and evaluated their in vivo biodistribution and toxicity.

2024-05-04 | PXD038850 | Pride

Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

Project description:To investigate differences in gene expression of synovial macrophages in experimental rat knee post traumatic osteoarthritis.

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Pain-driven transcriptome changes in synovium of knee osteoarthritis patients

Project description:Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA.

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Bulk RNA-seq of human knee osteoarthritis synovium

Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed RNA-seq using synovial tissues obtained from OA patients and non-OA patients.

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Regulatory constraint and selection during human knee evolution drive modern osteoarthritis risk

Project description:The evolution of human bipedalism exposed the knee to unique biomechanical challenges, requiring changes in knee anatomy giving rise to the modern-day configuration. In order to better understand the relationship between derived knee morphology and the genetic factors associated with osteoarthritis risk, we performed epigenetic profiling of murine forelimb/hindlimb growth plates to identify regulatory elements shaping formation of specific knee structures, identifying signals of ancient positive selection upon which more recent genetic drift overlaps risk-associated loci. Our functional analyses of an osteoarthritis-risk variant within a reproducibly-associated locus establishes a novel model for studying this degenerative disease.

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Transcriptome sequencing of synovial tissues of knee osteoarthritis rats.

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Project description:The aim of this study was to characterise the genome-wide DNA methylation profile of osteoathritis (OA) chondrocytes from both knee and hip cartilage, providing the first comparison of DNA methylation between OA and non-OA hip cartilage, and between OA hip and OA knee cartilage. The study was performed using the Illumina Infinium HumanMethylation450 BeadChip array. Genome-wide methylation was assesed in chondrocyte DNA extracted from 23 OA hip, 73 OA knee and 21 healthy hip controls (NOF - neck of femure samples). Keywords: Methylation profiling by array

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Single cell RNA-seq of human knee osteoarthritis synovium

Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed single cell RNA-seq using synovial tissues obtained from OA patients.

2025-01-07 | GSE283080 | GEO

RNA-seq of synovial membranes from a preclinical model of post-traumatic knee osteoarthritis to evaluate the effects of corticosteroid treatment

Project description:Yorkshire pigs received untreated unilateral ACL transection through a medial arthrotomy (INJ, n=6), transection with immediate injection of 20mg triamcinolone acetonide (TRI, n=6) or no surgery (CON, n=6). Synovial membranes were harvested two weeks after the injury in the lateral knee joint compartment. The whole biopsy was homogenised for RNA extraction. The objective of the experiment was to test if intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection and to characterize the synovial response using the described perturbations in combination with a functional genomics approach.

2016-01-29 | E-MTAB-4294 | biostudies-arrayexpress

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