The immunosuppressive mechanisms of mesenchymal stem cells are differentially regulated by platelet poor plasma and fetal bovine serum supplemented media

Abstract

Purpose: Mesenchymal Stem Cells (MSCs) can interact with and modulate the functions of all immune cells, suppressing both the innate and adaptive immune responses. Currently, most of the in vitro studies which have led to the description of MSC properties have resulted from MSC culture in the presence of fetal bovine serum (FBS), in spite of the recognition of FBS limitations and attempts to substitute this component from the MSC media.

Methods: Herein, we compare FBS and Platelet Poor Plasma (PPP) as MSC media supplements, according to Adipose-derived MSC (AMSC) phenotype, proliferation and immunoregulatory mechanisms.

Results: Interestingly, despite maintaining the classic phenotypic profile of MSCs, PPP cultured AMSCs showed impaired proliferative potential. Furthermore, our results clearly show that AMSC culture with PPP leads to decreased expression of soluble immunosuppressive factors, which resulted in decreased capacity of inducing regulatory T-cells (Tregs) generation by these cells. In contrast, PPP supplementation promoted enhanced VCAM-1 and ICAM-1 expression on AMSC surface. Therefore, AMSCs cultured with PPP showed limited potential to produce soluble immunomodulatory factors, indicating a reduced capacity to control the immune system thought paracrine activity.

Conclusion: Overall, our data sheds light on the importance of culture media supplementation for MSC immunomodulatory behavior, as well as serving as an alert regarding the complexity of replacing FBS in MSC culture.

Keywords: Fetal bovine serum; Immunoregulation; Mesenchymal stem cells; Platelet poor plasma; Regulatory T-cells.