Secretome Conveys the Protective Effects of ASCs: Therapeutic Potential Following Hemorrhagic Shock?

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Abstract

Objectives:

We tested whether resuscitation supplemented with a) rat adipose-derived stem cells (ASCs) or b) secretome (conditioned media) of ASCs can ameliorate inflammation, cell/organ injury, and/or improve outcome after Hemorrhagic traumatic shock (HTS).

Interventions:

Rats were subjected to HTS and a resuscitation protocol that mimics pre-hospital restrictive reperfusion followed by an adequate reperfusion phase. 20 minutes into the restrictive reperfusion, animals received an intravenous bolus of 2x106 cells (ASC group) or the secretome produced by 2x106 ASCs/24 h (ASC-Secretome group). Controls received the vehicle (Vehicle group). All rats were observed for 28-day survival.

Measurements and Main Results:

HTS-induced inflammation represented by IL-6 was inhibited in the ASC (80%, p < 0.001) and in ASC-Secretome (59%, p < 0.01) group at 48 h compared to Vehicle group. At 24 h, HTS-induced liver injury reflected in plasma alanine aminotransferase was ameliorated by 36% (p < 0.001) in both the ASC and ASC-Secretome groups when compared to the Vehicle. There was no effect on kidney function and/or general cell injury markers. HTS-induced a moderate 28-day mortality (18%) that was prevented (p = 0.08) in the ASC but not in the ASC-Secretome group (12%).

Conclusions:

Our data suggest that the ASC-secretome supplemented resuscitation following HTS, in absence of the stem cells, exerts anti-inflammatory and liver protective effects. Given its ease of preparation, storage, availability and application (in contrast to the stem cells) we believe that the cell free secretome has a better therapeutic potential in the early phase of an acute hemorrhagic shock scenario.

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