Decoding cargo sorting and selection for next-generation designer extracellular vesicles

The National Institute of General Medical Sciences awarded Howard University $190,291 for a Project Grant on September 1, 2026, to decode cargo sorting and selection mechanisms in mesenchymal stem cell-derived extracellular vesicles for next-generation therapeutic design.

The research investigates how MSCs regulate the molecular content of extracellular vesicles, focusing on integrin-mediated signaling and its influence on cargo selection. The project employs engineered peptide-polymer scaffolds that mimic extracellular matrix environments to systematically analyze how integrin signaling affects EV cargo composition. Two specific aims guide the work: quantifying the influence of individual integrin ligands on MSC EV cargo, and elucidating the impact of combinatorial integrin ligands on MSC-EV cargo. The findings will support rational design of extracellular vesicles for targeted therapies in regenerative medicine, immunotherapy, and cancer treatment.

The award period runs from September 1, 2026, through May 31, 2030, with work performed in Washington, DC. The award supports basic research under NIGMS's Biomedical Research and Research Training program (CFDA 93.859), which funds investigator-initiated research to advance understanding of biological processes and lay the foundation for advances in disease diagnosis, treatment, and prevention.

Abstract

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVS) are emerging as promising tools in regenerative medicine, immunotherapy, and cancer treatment. These nanoscale vesicles carry bioactive molecules that can modulate immune responses, support tissue repair, and inhibit tumor growth. However, the biological mechanisms that determine which proteins, rnas, and other molecules are selectively packaged into EVS remain unclear. This knowledge GAP limits the ability to design EVS with specific therapeutic functions. This research aims to uncover how mscs regulate the molecular content of their EVS, focusing on the role of integrins-cell surface receptors that mediate interactions with the extracellular matrix (ECM). Mscs express a wide range of integrins, which influence cellular behavior through signaling pathways triggered by adhesion to ECM components. We hypothesize that these integrin-substrate interactions affect EV formation and cargo selection. To investigate this, we will use engineered peptide-polymer scaffolds that mimic ECM environments and selectively engage specific integrin subtypes. These biomaterials will allow precise control over the cellular microenvironment and enable systematic analysis of how integrin signaling influences EV cargo composition. The project has two specific aims: (a) quantify the influence of individual integrin ligands on MSC EV cargo, and (B) elucidate the impact of combinatorial integrin ligands on MSC-EV cargo. By integrating biomaterials engineering with stem cell biology and EV analysis, this study will advance our understanding of EV cargo loading mechanisms. The findings will support the rational design of EVS for targeted therapies and contribute to the development of next-generation regenerative and immunomodulatory treatments. Additionally, this work will help build institutional capacity for cutting-edge biomedical research and foster interdisciplinary collaboration in the field of extracellular vesicle science.