No simple way to averaging out: Pooled mesenchymal stromal cells do not reflect average donor characteristics.

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)

Mesenchymal stromal cells (MSCs) are promising candidates for numerous regenerative therapies. Still, clinical translation is complicated by the heterogeneity of MSCs and related shortcomings in preclinical research. Pooling MSCs from multiple donors is increasingly being advocated as an effective way to mitigate donor variability. However, it remains unclear whether the range of individual cell characteristics is equally reflected in pooled cultures, or if pooling rather leads to a homogenized cell population dominated by the fittest donor, which would lead to skewed results. This study investigates whether MSC pools are functionally representative for their respective donor MSCs and whether dominant donors emerge over time. MSCs from nine human donors were categorized into low-, middle-, and high-fitness groups. Individual MSCs were then pooled according to their fitness groups, complemented by a mixed-fitness pool. Functional assays for proliferation, metabolic activity, differentiation, migration and senescence were performed to evaluate the pools versus the individual MSCs. Donor representation within pools was tracked using fluorescence microscopy and qPCR. The high-fitness pool, as well as its individual donor MSCs, displayed the most rapid proliferation and highest metabolic activity. However, while for proliferation, the pool data aligned well with the individual donor

Evidence level

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

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