Researchers found that newborn immune cells regenerate heart tissue by producing thromboxane. Mimicking this process in adults could revolutionize heart attack recovery.
- A study in experimental animals shows that the immune system heals the heart differently depending on age.
- In newborns, immune cells recognize and remove dying cells, triggering the release of bioactive lipids that promote heart regeneration.
- These findings could lead to treatments that “reprogram” the adult immune system to improve heart healing.
Why Newborns Can Heal, but Adults Can’t
Newborns with heart complications have an advantage that adults lack — the ability to regenerate heart tissue. Their developing immune systems help repair damage, while in adults, heart injuries often lead to scar tissue formation, increasing the risk of heart failure.
A new study from Northwestern Medicine, conducted in experimental animals, reveals a key difference in how the immune system responds to heart damage at different ages. The research focuses on macrophages, immune cells involved in tissue repair, and how their function differs between newborns and adults following a heart attack.
The study is set to be published today (February 11) in the journal Immunity.
“By mimicking the effects of thromboxane, we might one day improve tissue repair after a heart attack in adults.”
Connor Lantz
A Potential Path to Reprogramming Healing
“Understanding why newborns can regenerate their hearts while adults cannot will open the door to developing treatments that could ‘reprogram’ adult macrophages,” said first and co-corresponding author Connor Lantz, lead scientist of the bioinformatics core at the Comprehensive Transplant Center at Northwestern University Feinberg School of Medicine.
In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.
“By mimicking the effects of thromboxane, we might one day improve tissue repair after a heart attack in adults,” Lantz said.
How the Study Worked
The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.
The Key to Heart Regeneration?
Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way — after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.
Reference: “Early Age Efferocytosis Directs Macrophage Arachidonic Acid Metabolism for Tissue Regeneration” 11 February 2025, Immunity.
Edward B. Thorp, professor of experimental pathology at Feinberg, is a co-corresponding study author.
