Level D· Preclinical EvidenceLaboratory Study

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

Chatterjee P., Stevens HY., Kippner LE., Yeago C., Drissi H., Mautner K.

Laboratory Study on Knee Osteoarthritis, Osteoarthritis, published in Mol Ther Nucleic Acids (2026) — summary generated from the PubMed abstract.

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Study type
Laboratory Study
Journal
Mol Ther Nucleic Acids (2026)
Country
United States
Reported sample size
PMID
41717289
DOI
10.1016/j.omtn.2026.102839

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

What this study does not prove

  • This study does not prove SVF is an approved treatment or a replacement for standard care.
  • This is preclinical work; animal or laboratory results cannot be applied to humans.

Evidence level

Evidence comes from animal or laboratory studies and has not been confirmed in humans.

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