Principal Investigator: Shibani Pati, MD, PhD
Organization: University of California San Francisco
The main goal of this project is to develop and test dried stem cell products (lyophilized-MSCs and lyophilized-MSC EVs) for their potential to attenuate the Endotheliopathy of Trauma and mitigate outcomes in severely injured patients in need of pre-hospital care. The rationale for the need for dried cell therapy products can be attributed to the cumbersome, logistically challenged and costly process of transporting and storing cellular products. This often leads to compromise of the product therapeutically and a lack of availability to patients in need. We have extensive pre-clinical data supporting the use of MSCs and MSC-EVs in hemorrhagic shock (HS)-induced organ failure. We have experience with lyophilizing EVs from platelets and have data demonstrating their functionality in mitigating the EOT.
Leveraging knowledge developed by industry involved in the production of dried (spray, freeze or lyophilized) dried blood products, we will attempt to produce a dried mesenchymal stem cell (MSC) product and a dried MSC extracellular vesicle (EV) product that can mitigate the endotheliopathy of trauma, a process that contributes to organ failure and death in trauma. Utilizing two technologies for drying, freeze drying and spray drying we will conduct pilot studies to determine which method produces the optimal functional products. We will test lyo-MSCs and lyo-MSC EVs in an established pre-clinical murine model of polytrauma with hemorrhage, shock and TBI. It is our goal to determine what the best stabilizing excipient is for the dried MSCs or MSC EVs. The main objectives of the project are listed below.
Scope/Project Objective:
Objective 1: To optimize the methodology and production of lyo-MSCs and lyo-MSC EVs that allows cell product reanimation to therapeutic functionality after reconstitution.
Objective 2: To determine if lyo-MSCs and lyo-MSC EVs mitigate outcomes in a murine model of polytrauma with TBI and hemorrhagic shock.