Single-cell transcriptomics of multi-site cell therapy in osteoarthritis: Tissue-specific treatment correlations.

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Knee-osteoarthritis (knee OA) is a prevalent joint disorder lacking Food and Drug Administration-approved cell therapies to halt progression. This study uses single-cell RNA sequencing to analyze bone marrow aspirate concentrate (BMAC) and stromal vascular fraction (SVF) samples in a clinical trial of autologous cell therapies. Trial site-specific variability was significant in BMAC, necessitating tailored normalization, whereas SVF was less affected, likely due to uniform subcutaneous fat sampling. Variance partitioning and tensor decomposition identified site effects in BMAC but revealed shared pathways across cell types in both tissues. Differential gene expression (DEG) analysis between responders and non-responders yielded no significant findings, although likelihood ratio test (LRT) revealed enrichment for DEG patterns linked to disease severity, potentially masked by patient heterogeneity. Key BMAC pathways included oxidative phosphorylation, unfolded protein response, and tumor necrosis factor alpha ( TNF-α ) signaling. Cell-cell communication analysis suggested enhanced human leukocyte antigen (HLA) signaling in non-responder MSCs (mesenchymal stromal cells), consistgenesent with inflammation, while responders showed more coordinated immune interactions. BMAC-MSCs promoted chondrocyte proliferation, whereas SVF-MSCs emphasized immune regulation. This study suggests tha

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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