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Newswise — This article discusses the study by Xiao et al, which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells (N-hUCMSCs) in a mouse model of knee osteoarthritis. The results showed that N-hUCMSCs alleviated osteoarthritis-related cartilage damage and inflammation comparably to both serum-cultured hUCMSCs and hyaluronic acid. While these findings broaden the potential clinical utility of N-hUCMSCs by circumventing certain drawbacks of serum-based cultures, the equivalence in efficacy raises important questions. First, how do N-hUCMSCs differ phenotypically from serum-cultured hUCMSCs, particularly in terms of proliferation rate, replicative capacity, and senescence profile? Second, what advantages might N-hUCMSCs offer over hyaluronic acid - a well-established therapy - beyond avoiding xenogeneic components and ethical concerns? Future research should focus on long-term phenotypic stability, sustained functional benefits, safety profiles, and mechanistic insights to ascertain whether N-hUCMSCs can surpass current standards of care.

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Core Tip: This article evaluates the study by Xiao et al on using serum-free cultured human umbilical cord mesenchymal stem cells (N-hUCMSCs) to treat knee osteoarthritis in a mouse model. Although N-hUCMSCs matched the efficacy of both serum-cultured hUCMSCs and hyaluronic acid, future research must clarify how N-hUCMSCs differ in long-term proliferative capacity and senescence profiles compared to their serum-cultured counterparts. Additionally, since hyaluronic acid is an established osteoarthritis treatment, demonstrating clear advantages, such as fewer side effects, more durable outcomes, or enhanced cartilage regeneration, will be crucial for justifying the clinical adoption of N-hUCMSCs.

• Citation: Lin F, Ma KX, Ding Y, Liang XT. Efficacy equivalence but hidden hurdles: Can serum-free human umbilical cord mesenchymal stem cells translate to clinically superior osteoarthritis therapy. World J Stem Cells 2025; 17(3): 104566
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