A new study from Northwestern Medicine has uncovered a key difference in how newborns and adults heal from heart damage. The research, conducted in experimental animals, sheds light on why infants can regenerate heart tissue while adults suffer from long-term scarring. It highlights the critical role of immune cells called macrophages in driving heart repair.
How Newborns Regenerate Heart Tissue
In newborns, macrophages perform a process known as efferocytosis, which allows them to recognize and consume dying cells. This process triggers the production of a lipid called thromboxane, which signals heart muscle cells to divide and regenerate damaged tissue. However, as humans age, macrophages become less efficient at producing thromboxane, leading to weaker repair signals and increased scar tissue formation instead of regeneration.
“Understanding why newborns can regenerate their hearts while adults cannot open the door to developing treatments that could ‘reprogram’ adult macrophages,” said Connor Lantz, first and co-corresponding author of the study and lead scientist at Northwestern University Feinberg School of Medicine.
Key Differences Between Newborn and Adult Hearts
The research team examined heart injury responses in mice of different ages, including newborns (one day old) and adults (eight weeks old). They found that newborn macrophages had higher levels of a MerTK receptor, which enhanced their ability to engulf dying cells. When researchers blocked this receptor in newborn mice, their ability to regenerate heart tissue was lost, making their healing process resemble that of adult mice.
Further analysis revealed that newborn macrophages produce more thromboxane A2, a molecule that stimulates heart muscle cells to multiply and repair damage. Additionally, newborn heart muscle cells are more responsive to thromboxane A2, adapting their metabolism to support regeneration. However, this mechanism is significantly weaker in adults, preventing effective tissue repair after a heart attack.
A Potential Path Toward Heart Regeneration in Adults
The findings suggest that mimicking the effects of thromboxane A2 in adult patients could one day enhance heart tissue repair following a heart attack. Suppose researchers can develop treatments encouraging adult macrophages to behave more like their newborn counterparts. In that case, reducing scar tissue formation and improving heart function after injury may be possible.
The study, “Early Age Efferocytosis Directs Macrophage Arachidonic Acid Metabolism for Tissue Regeneration,” was co-authored by Edward B. Thorp, a professor of experimental pathology at Feinberg. The research represents a significant step toward understanding how the immune system influences heart repair and could lead to future regenerative therapies for heart disease.
Reference: Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp. Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration. Immunity, 2025.
