Overcoming Immune Barriers to Pluripotent Stem Cell-based Cardiac Regeneration

 

PI: Timothy Kamp, professor of Medicine

Co-PIs:

Matthew Brown, assistant professor of Surgery

Sean Palecek, professor of Chemical and Biological Engineering

Igor Slukvin, professor of Pathology and Laboratory Medicine

Description: Heart failure (HF) reflects a major health problem and cause of death that is often due to an irreversible loss of heart muscle cells. Stem cell-based therapies offer a promising way to regenerate damaged heart tissue, but a key obstacle stands in the way: immune rejection. This project aims to overcome that barrier by developing a new, human-relevant testing system coupled with innovative strategies to promote drug-free immune acceptance.

The team will use advanced humanized mouse models with functional human immune systems to study how transplanted stem cell-derived heart tissues are recognized and rejected. They will test two complementary approaches: 1) creating mixed immune chimerism that teaches the body to tolerate donor cells, and 2) genetically engineering the donor cells to evade immune killing. By combining these strategies, they aim to enable long-lasting, functional heart repair without the need for harmful immunosuppressive drugs, bringing regenerative therapies closer to widespread clinical application.