Mesenchymal Stem Cell Extracellular Vesicles As A New Treatment Paradigm in Solid Abdominal Organ Transplantation: A Case Series.

Solid abdominal organ transplantation is fraught with variable rates of rejection and graft versus host disease. We sought to determine the safety and efficacy of an advanced extracellular vesicle (EV) investigational product (IP) derived from mesenchymal stem cells (MSC) in the transplant patient population. Seven separate eINDs were filed with the FDA for the emergency treatment of rejection of an isolated intestinal graft (n=2), liver allograft graft (n=2), modified multivisceral graft (n=3), and GVHD in isolated intestinal transplant patients (n=2). 15 mL of IP was administered intravenously on Day 0, 2, 4 and this treatment cycle was repeated up to four times in each patient depending on the treatment protocol allowed by the FDA. Safety (adverse event reporting) and efficacy (clinical status, serologies, and histopathology) were evaluated. There were no adverse events related to IP. All patients had improvement in clinical symptoms within 24 hours, improved serologic laboratory evaluation, improved pulmonary symptoms and dermatologic manifestations of GVHD, and complete histologic resolution of graft inflammation/rejection within 7 days of investigational product administration. Systemic use of a MSC derived EV IP was successful in achieving histological clearance of intestinal, liver and multivisceral graft inflammation, and skin and pulmonary manifestations of GVHD.