The project investigated why the adult mammalian heart cannot regenerate and focused on investigating Treg cells. The neonatal heart can regenerate after injuries in the first week, yet the adult heart lacks this ability. Researchers aimed to replicate neonatal cellular and molecular mechanisms to promote adult cardiac repair. Treg cells demonstrated their ability to drive regeneration in multiple systems, including the heart. Previous work showed Treg cells are essential for neonatal heart regeneration, and promote cardiomyocyte proliferation through paracrine secretion of CCL24, GAS6, and Areg.

In experiments with Foxp3-hCD2 mice, purified Treg cells were subjected to lytic antibody-mediated ablation. Adoptive transfer of splenic hCD2+ Treg cells from Foxp3-hCD2 mice contributed to neonatal heart regeneration, reducing cardiac fibrosis and improving cardiac function in Treg-deficient NOD/SCID mice. Depletion of Treg cells led to impaired regeneration. This project aimed to study molecular mechanisms of Treg-mediated regeneration and apply the findings to enhance adult heart repair using Treg pathways.