Adipose derived stem cell activation by macrophages and tendon fibroblasts.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• 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)

Aims Tendon injuries are common, and healing often fails due to an over-exuberant inflammatory response and a lack of regeneration. Inflammatory cells play key roles in these processes, with a balance between classically activated pro-inflammatory M1 macrophages and alternatively activated inflammatory resolving M2 macrophages. Adipose-derived mesenchymal stem cells (ASCs) can dampen the pro-inflammatory effectsof macrophages, promote a regenerative environment, and enhance healing. Therefore, the goal of the study was to understand how ASCs are activated by macrophages in vitro . Methods In vitro co-culture experiments were carried out with ASCs, macrophages, and tendon fibroblasts. RNA-seq and qRT-PCR were performed to determine expression patterns of activated ASCs. Results M1 macrophages prompted ASCs to upregulate pro-inflammatory signaling, matrix remodeling, and cytokine production pathways, while downregulating those related to cell adhesion and cell cycle. Conversely, TFs prompted ASCs to upregulate pathways involved in cell cycle and cytoskeleton remodeling, and to downregulate pathways associated with immune cell adhesion, inflammatory mediator production, and protein metabolism. Conclusions The cell-specific activation profiles indicate a possible switch in ASC paracrine signaling depending on the context, from a pro-inflammatory pattern in response to M1 macrophage

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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