Alteration of Transcriptomic Profile and Antiseptic Efficacy of Adipose-Derived Mesenchymal Stromal/Stem Cells Under Different Culture Conditions

Abstract

Mesenchymal stromal/stem cells (MSCs) are a promising therapeutic agent for various diseases, including sepsis. However, translating MSC therapy to clinical applications remains challenging due to variations in the properties of MSCs under different preparation conditions. In this study, the gene expression profiles of human adipose-derived mesenchymal stromal/stem cells (ADSCs) under different culture conditions were compared in relation to their therapeutic efficacy for sepsis. Results showed that ADSCs cultured in media supplemented with human platelet lysates (hPL-ADSCs) exhibited a smaller cell size and higher proliferative capacity, while ADSCs cultured in media supplemented with fetal bovine serum (FBS-ADSCs) showed a broader and flatter shape. Both hPL-ADSCs and FBS-ADSCs exhibited a protective effect in a mouse model of sepsis; however, hPL-ADSCs displayed a better potency for immunosuppressive function, as evidenced by a better improvement of survival rate and further reduction of tissue injury and infectious biomarkers (ALT and PCT). Furthermore, hPL-ADSCs caused a more anti-inflammatory transcriptomic shift, while FBS-ADSCs led to more depression of pro-inflammatory transcriptomic response. This study thus demonstrates that both hPL-ADSCs and FBS-ADSCs are effective for anti-septic therapy via different mechanisms of inflammatory manipulation, although hPL-ADSCs may imply a better preference.