Starvation and Inflammation Modulate Adipose Mesenchymal Stromal Cells’ Molecular Signature

TL;DR

This study shows that starvation can reverse the inflammatory effects of priming adipose-derived stem cells, which is important for regenerative medicine.

Contribution

The novel finding is that starvation can modulate the secretome of IL1β-primed ASCs, reversing their pro-inflammatory effects.

Findings

IL1β priming increases inflammatory mediators and reduces anti-inflammatory potential in ASCs.

Starvation reverses the pro-inflammatory effects of IL1β-primed ASCs on chondrocytes.

Starvation significantly modulates the molecular profile of ASCs' secretome.

Abstract

Mesenchymal stromal cells (MSCs) and their released factors (secretome) are intriguing options for regenerative medicine approaches based on the management of inflammation and tissue restoration, as in joint disorders like osteoarthritis (OA). Production strategy may modulate cells and secretome fingerprints, and for the latter, the effect of serum removal by starvation used in clinical-grade protocols has been underestimated. In this work, the effect of starvation on the molecular profile of interleukin 1 beta (IL1β)-primed adipose-derived MSCs (ASCs) was tested by assessing the expression level of 84 genes related to secreted factors and 84 genes involved in defining stemness potential. After validation at the protein level, the effect of starvation modulation in the secretomes was tested in a model of OA chondrocytes. IL1β priming in vitro led to an increase in inflammatory mediators’ release and reduced anti-inflammatory potential on chondrocytes, features reversed by subsequent starvation. Therefore, when applying serum removal-based clinical-grade protocols for ASCs’ secretome production, the effects of starvation must be carefully considered and investigated.

Figures