Putative critical quality attribute matrix identifies mesenchymal stromal cells with potent immunomodulatory and angiogenic "fitness" ranges in response to culture process parameters.

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)

Adipose-derived mesenchymal stromal cells (MSC(AT)) display immunomodulatory and angiogenic properties, but an improved understanding of quantitative critical quality attributes (CQAs) that inform basal MSC(AT) fitness ranges for immunomodulatory and/or angiogenic applications is urgently needed for effective clinical translation. We constructed an in vitro matrix of multivariate readouts to identify putative CQAs that were sensitive enough to discriminate between specific critical processing parameters (CPPs) chosen for their ability to enhance MSC immunomodulatory and angiogenic potencies, with consideration for donor heterogeneity. We compared 3D aggregate culture conditions (3D normoxic, 3D-N) and 2D hypoxic (2D-H) culture as non-genetic CPP conditions that augment immunomodulatory and angiogenic fitness of MSC(AT). We measured multivariate panels of curated genes, soluble factors, and morphometric features for MSC(AT) cultured under varying CPP and licensing conditions, and we benchmarked these against two functional and therapeutically relevant anchor assays - in vitro monocyte/macrophage (MΦ) polarization and in vitro angiogenesis. Our results showed that varying CPP conditions was the primary driver of MSC(AT) immunomodulatory fitness; 3D-N conditions induced greater MSC(AT)-mediated MΦ polarization toward inflammation-resolving subtypes. In contrast, donor heterogeneit

Evidence level

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

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