Macrophages of the innate immune system play an important role in coordinating the intricate dance of cell populations that takes place during regeneration from injury. Differences in macrophage behavior may be key to the exceptional regenerative capacities of species such as salamanders that can regrow entire organs, and possibly also in the few mammalian species and genetically altered lineages capable of noteworthy feats of regeneration.

Researchers here make a most interesting discovery, finding that in mice there are populations of macrophages capable of coordinating greater than normal regeneration following injury to the heart, such as that resulting from a heart attack. This regeneration doesn’t take place because the macrophages arrive too late to prevent the formation of scar tissue; regeneration is already well advanced by the time they are present in any significant number. This suggests that regenerative therapies based on manipulation of macrophage behavior are plausible for the near future, as it is always easier to adjust an existing mechanism than it is to build something completely novel.

Macrophages are white blood cells that live in organs and are key components of our immune system. They have a well-established ability to fight infections, but more recently, have been shown to help promote repair and regeneration of tissues. Researchers have found that instead of a single type of macrophage, there are at least four types that live within the uninjured heart, and that number increases to 11 after a heart attack, which indicates the immune system behaves in much more complex fashion than was imagined.

First, they found that neonatal-like macrophage cells are lost after a heart attack in adults, which could explain why the adult heart may not heal itself as well as the neonatal heart. In very young animals, neonatal macrophages increase in number and are very effective at triggering the regrowth of heart muscle and blood vessel cells. “Genetically removing neonatal-like macrophages at the time of the heart attack in adult animals worsens heart function most profoundly at the region of the heart separating injured and uninjured heart muscle – the only zone of the adult heart where they increase in number.”

Researchers also found large numbers of macrophages are attracted to the heart after a heart attack, and a small number enter into the neonatal state, except, too late. By the time they arrive on site after a heart attack, a scar has formed in the heart in the place of heart muscle. “Each cell has a unique role to play in the human body, but our next question is: how can we guide a cell that enters the heart into a neonatal state more efficiently and, ultimately, more effectively?”


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