Timing of intra-articular injection of adipose-derived mesenchymal stem cells affects cartilage integrity and IL-18 expression in spontaneous osteoarthritis: A preclinical study.

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)

Osteoarthritis (OA) is a progressive joint disease primarily characterized by cartilage degradation. A phase I/II clinical trial demonstrated the therapeutic efficacy of a human adipose-derived mesenchymal stem cell (ADMSC) product in patients with knee OA. However, it remains unclear whether its efficacy varies with disease stage or whether a single intra-articular dose offers sustained protection. In this study, we used STR/ort mice-a spontaneous OA model-to evaluate the effects of a single ADMSC injection administered during either early or advancing-stage OA. An additional group received early-stage treatment and was analyzed at a later time point to assess durability. Cartilage integrity, chondrocyte phenotypes, serum cytokines, and subchondral bone structure were examined at three defined time points. Early ADMSC injection significantly reduced matrix-nonproducing chondrocytes, lowered Osteoarthritis Research Society International (OARSI) scores, suppressed aggrecan fragment and matrix metallopeptidase 13 (MMP-13) expression, and increased SRY-box transcription factor 9 (SOX9) levels. In situ RNA hybridization showed that ADMSC xenografts transiently adhered to the cartilage surface and remained detectable post-injection. Micro-computed tomography (micro-CT) demonstrated restored trabecular architecture, while cytokine profiling revealed reduced interleukin-18 (IL-18) lev

Evidence level

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

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