We have just described a new mechanism of immune modulation of mesenchimal stem cells (MSCs), confirmed in vitro and in vivo in a translational model of heart infarct in swine. The study is part of the ongoing collaboration with Dr Santiago Roura, Dra Carol Gálvez Montón and Dr Antoni Bayés Genís of the ICREC group at the Germans Trias i Pujol Research Institute (IGTP).

In the context of myocardial infarction, tissue necrosis (uncontrolled cell death) leads to the release of inflammatory molecules, including great amounts of ATP, which triggers tissue inflammation. This inflammatory signals recruit immune cells to the myocardium, being monocytes one of the first ones to infiltrate to the tissue. Depending on the immune response generated by monocytes, releasing pro- or anti-inflammatory mediators, tissue injury or tissue repair and regeneration will be promoted, respectively.

In this study, we could demonstrate how MSCs are able to modulate monocytes towards a regulatory phenotype, promoting the secretion of anti-inflammatory cytokines. At the same time, the contact with MSCs induced functional CD73 expression on monocytes. Together with the constitutive expression of CD39, these monocytes are then suited to sequentially hydrolise pro-inflammatory ATP to Adenosine, a potent anti-inflammatory mediator.

Moreover, these results were confirmed in a translational swine model of myocardial infarction: host monocytes expressed CD73 only when animals were treated with MSCs after the induction of myocardial infarction.

As the first author Marta Monguió-Tortajada explains, “these results indicate that MSCs would be able to modify the patient’s innate immune cells, skewing monocytes towards a regulatory phenotype, which would include the capacity to reduce ATP levels and increase anti-inflammatory Adenosine”, and adds, “this new immune regulatory mechanism helps explain the long-lasting, beneficial effects that MSC treatment has in myocardial infarction“.

The results have been published in the Open-access journal Frontiers in Immunology (IF 2016: 6.429).

graphical summary CD73 MMT

Figure: Monocytes expressed CD73 after MSC treatment of MI. Left: Pigs were locally treated with cardiac adipose tissue MSCs (cATMSC) by covering the myocardial infarcted area with a bioengineered 3D graft embedded with cATMSCs. Right: Infiltrating monocytes (CD163+, in white) were found in the injured myocardium, which expressed CD73 (red) only in those animals treated with cATMSCs after an induced myocardial infarction.

Reference:

Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and in a Swine Model of Myocardial Infarction In Vivo. Monguió-Tortajada M, Roura S, Gálvez-Montón C, Franquesa M, Bayes-Genis A, and Borràs FE. Frontiers in Immunology 2017 November 20 (1577). doi:10.3389/fimmu.2017.01577.

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