Endothelial Progenitor Cell-Derived Exosomes as a Novel Therapeutic in Sepsis

Technology: MUSC researchers have developed a novel therapy to treat sepsis and Acute Respiratory Distress Syndrome (ARDS) using endothelial progenitor cell-derived (EPC) exosomes, which reduced lung and organ injury, inflammation response, and increased survival rate in a mouse model. Data gathered showed that in a sepsis model, IV administration of EPC exosomes significantly increased the survival rate of Cecal Lingation Puncture (CLP)-induced sepsis mice compared to placebo and non-EPC exosome groups (figure 1).

CLP-induced sepsis mice also had a significant cytokine and chemokine reduction after treating with EPC-exosomes. Organ injury (AST, ALT, BUN level), vascular leakage (in lung and kidney), and lung edema were also suppressed after administering EPC-exosomes to CLP-induced sepsis mice (figure 2).

In a lipopolysaccharide (LPS)-induced acute lung injury model, the LPS-induced lung injury and inflammation was reduced (figure 3). Intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation (see published reference).

 

Overview: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The acute respiratory distress syndrome (ARDS) is a complex and deadly disease characterized by inflammation and lung permeability leading to alveolar edema and organ failure. In the US alone, there are over 1 million hospitalized cases of sepsis per year, resulting in an estimated cost of $20 billion annually to the US healthcare system. Patients developing ARDS require treatment in an intensive care unit. There is currently no specific and effective therapy targeting the inflammation and vascular dysfunction associated with sepsis and ARDS.

 

Publication: 

Yue Zhou at al., “Exosomes from Endothelial Progenitor Cells Improve the Outcome of a Murine Model of Sepsis.”, Molecular Therapy, May 2018, 26, 5, 1375-1384.

Yue Zhou at al., “Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury.”, Critical Care, Feb, 2019, 23:44.

 

Inventors:  Hongkuan Fan, Andrew Goodwin, Perry V. Halushka, James A. Cook, Yue Zhou     

  

Patent Status: WO 2019/168977US20200390822A1 

 

MUSC-FRD Technology ID: P1810

 

 

 

Patent Information: