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Integration of clinical and multi-omics data identifies changes in the composition and activity of autologous-conditioned plasma that correlate with outcomes in patients with knee osteoarthritis

ABSTRACT: Autologous blood-derived products such as platelet-rich plasma (PRP) or autologous-conditioned plasma (ACP) have been used for managing symptoms of knee osteoarthritis (OA); however, the outcomes are highly variable due to limited information about the characteristics of these products, and how they impact clinical responses. We hypothesized that the clinical response ACP in patients with knee OA will correlate with the biologic activity and composition of the ACP administered. To test our hypothesis, we enrolled 51 patients with mild-moderate knee OA. We collected clinical information at baseline, and patient reported outcomes at 6 weeks and 6 months after ACP injection. We evaluated the composition of ACP by multiplex ELISA, and the biologic activity of the same aliquots using an in vitro biologic assay paired with gene expression analyses. Patients were stratified as responders and non-responders to ACP based on achievement of minimal clinically important differences in patient reported outcomes collected at 6 weeks and 6 months. RNA sequencing revealed that ACP modulates inflammatory responses in a co-culture of macrophages and fibroblast-like synoviocytes (fibroblasts); using this data, we selected specific genes to evaluate the biologic activity of ACP in vitro. Comparison of ACP from responders and non-responders revealed differences in the composition and activity of ACP between these groups. By integrating clinical and multi-omics data, we uncovered changes in the composition and biologic activity of ACP that may correlate with outcomes in knee OA patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157364 | GEO | 2021/09/02

REPOSITORIES: GEO

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Project description:Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA. Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score >3, AhlbÃ¤ck Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using quantitative RT-PCR. Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (COL2A1, COMP, aggrecan, CRTL1, SOX9) and genes involved in matrix synthesis (biglycan, COL9A2, COL11A1, TIMP4, CILP2) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (COL10A1, RUNX2, periostin, ALP, PTHR1, MMP13, COL1A1, COL3A1) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, were differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated. Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA and OA chondrocytes fulfill the requirements for matrix-associated ACT. Experiment Overall Design: Gene expression profiles of monolayer cultures (ML; passage 2) and Hyaff-11 scaffold cultures (3D; 14 days in vitro) of chondrocytes from 3 normal donors (ND; underwent ACT treatment) and 3 donors suffering from Osteoarthritis (OA; underwent knee replacement surgery) were determined. Comparative analyses between 3D and ML cultures (3D vs. ML) were performed to assess differentiation capacity of ND and OA chondrocytes. Furthermore, OA-related differences were determined comparing OA and ND monolayers as well as scaffold cultures (each OA vs. ND).

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Integration of clinical and multi-omics data identifies changes in the composition and activity of autologous-conditioned plasma that correlate with outcomes in patients with knee osteoarthritis

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