The Safety and Efficacy of Extracellular Vesicles for Use in a Model of Acute Traumatic Coagulopathy Induced By Polytrauma and Hemorrhagic Shock

Date

2020

Authors

Chance, Tiffani Celeste

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Abstract

Induced traumatic coagulopathy associated with polytrauma and hemorrhagic shock presents challenges for immediate management and treatment due to its severe nature. Further complications arise from the lack of immediately available blood products for treatment- particularly in military environments. Thus, there is a need for novel therapeutics to bridge the gap of trauma care until more advanced care and supply of blood products can be had.

Extracellular vesicles (EVs) are emerging as a potential cell-free therapeutic for multiple forms of trauma due to their regenerative potential and ability to be lyophilized. These combined aspects make EVs a possible alternative to blood products to treat trauma and hemorrhagic shock. Therefore, the safety and efficacy of EVs isolated from multiple sources were evaluated for use in a rat model of polytrauma and hemorrhagic shock.

EVs isolated from adipose and bone-marrow mesenchymal stem cells (MSCs) under spheroid or monolayer culture were used for aims 1 and 2. AIM 1: Evaluate EV hemostatic potential as a safety precaution for recipients who might present as coagulopathic. EVs from adipose MSC sources displayed significantly elevated hemostatic potential. AIM 2: Assess EV angiogenic potential, an important component in wound healing, in relation to mitochondrial health. Adipose and spheroid derived EVs best promoted angiogenesis in relation to mitochondrial health. EVs from cardiosphere cells (CDC-EVs), a viable alternative to MSC-EVs, were utilized in aim 3. AIM 3: Determine EV hemostatic profile and therapeutic efficacy in a rat model of acute traumatic coagulopathy induced by polytrauma and hemorrhage. CDC-EVs have little impact on coagulation and show potential as an anti-shock therapeutic.

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Keywords

Coagulation, Extracellular Vesicles, Hemorrhage, Military Medicine, Polytrauma, Shock

Citation

Department

Biomedical Engineering