Extracellular vesicles derived from cardiosphere-derived cells as a potential antishock therapeutic
Tiffani C Chance1, Xiaowu Wu, Jeffrey D Keesee
1From the Coagulation and Blood Research (Blood) (T.C.C., X.W., J.D.K., J.G.-M., C.L.S., B.L., A.P.C., J.A.B.), United States Army Institute of Surgical Research, San Antonio, Texas; Capricor Therapeutics Institute (J.J.M., K.A.P., L.R.-B., N.A.A., L.S.M.), Beverly Hills, California; Department of Biological Chemistry (S.J.G.), Johns Hopkins, Baltimore, Maryland; and Department of Biomedical Engineering (C.R.R.), The University of Texas at San Antonio, San Antonio, Texas.
Background:
Extracellular vesicles (EVs) isolated from cardiosphere-derived cells (CDC-EVs) are coming to light as a unique cell-free therapeutic. Because of their novelty, however, there still exist prominent gaps in knowledge regarding their therapeutic potential. Herein the therapeutic potential of CDC-EVs in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock is outlined.
Methods:
Extracellular vesicle surface expression of procoagulant molecules (tissue factor and phosphatidylserine) was evaluated by flow cytometry. Extracellular vesicle thrombogenicity was tested using calibrated thrombogram, and clotting parameters were assessed using a flow-based adhesion model simulating blood flow over a collagen-expressing surface. The therapeutic efficacy of EVs was then determined in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock.
Results:
Extracellular vesicles isolated from cardiosphere-derived cells are not functionally procoagulant and do not interfere with platelet function. In a rat model of multiple injuries and hemorrhagic shock, early administration of EVs significantly reduced the elevation of lactate and creatinine and did not significantly enhance coagulopathy in rats with acute traumatic coagulopathy.
Conclusion:
The results of this study are of great relevance to the development of EV products for use in combat casualty care, as our studies show that CDC-EVs have the potential to be an antishock therapeutic if administered early. These results demonstrate that research using CDC-EVs in trauma care needs to be considered and expanded beyond their reported cardioprotective benefits.
Insights
Cardiosphere-derived cell extracellular vesicles (CDC-EVs) show potential as an antishock therapy for acute traumatic coagulopathy. Early administration reduced organ damage markers without worsening clotting in a rat model.
Area of Science:
- Regenerative Medicine
- Cell-Free Therapeutics
- Trauma Care Research
Background:
- Cardiosphere-derived cell extracellular vesicles (CDC-EVs) are emerging as a novel cell-free therapeutic.
- Knowledge gaps exist regarding the full therapeutic potential of CDC-EVs.
- This study investigates CDC-EVs in a rat model of acute traumatic coagulopathy.
Purpose of the Study:
- To evaluate the therapeutic potential of CDC-EVs in acute traumatic coagulopathy.
- To assess the impact of CDC-EVs on coagulopathy and organ function in a trauma model.
- To determine if CDC-EVs possess procoagulant properties.
Main Methods:
- Flow cytometry to evaluate surface expression of procoagulant molecules on EVs.
- Thrombogenicity and clotting assays to assess EV impact on coagulation.
- Evaluation of therapeutic efficacy in a rat model of multiple injuries and hemorrhagic shock.
Main Results:
- CDC-EVs were not functionally procoagulant and did not affect platelet function.
- Early EV administration in rats with traumatic coagulopathy reduced lactate and creatinine levels.
- No significant enhancement of coagulopathy was observed with early EV administration.
Conclusions:
- CDC-EVs demonstrate potential as an early antishock therapeutic in trauma care.
- Findings support further research into CDC-EVs for combat casualty care.
- The therapeutic applications of CDC-EVs may extend beyond cardioprotection into trauma management.
