Marsupials are a quirky group of animals. They are one of three types of mammals, their distinctive feature is that their young are born prematurely and the internal organs and cells of the offspring continue to grow and divide for weeks after birth. Think of a kangaroo joey growing in a mother’s pouch.
A team of scientists at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan has also discovered that baby possums have an extra trick up their sleeve: they can regenerate their heart muscle a few weeks after birth.
And by modifying a few choice genes, the researchers were able to repair the damaged heart of a non-marsupial – mice – a week after birth.
The team hopes their research – published in the journal Circulation – will be able to contribute to new developments in regenerative cardiac medicine.
As with all tissue regeneration, heart repair requires the birth of new cells, which can only happen through the process of cell division. In most mammalian hearts, muscle cell division may continue just after birth, but disappear quickly after a few days.
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“No mammal species studied to date has been found capable of producing a meaningful regenerative response to myocardial injury later than a week after birth,” the team write in their new paper.
In humans and other mammals, damaged heart muscle – such as a heart attack – cannot be repaired naturally because mature heart muscle cells do not regenerate.
The team hypothesized that this may not be the case in marsupials. Because the hearts of marsupials continued to grow after birth — because their cells retain the ability to divide — the hearts were also able to regenerate after injury.
The researchers used the opossum (Monodelphis domestica) for the study, and they found that their hearts actually continued to grow for several weeks after birth.
When the team caused heart damage after two weeks, the heart repaired itself within a month, indicating that as long as heart cells continue to divide, the heart can be repaired.
“Heart regeneration for more than two weeks after birth in the opossum is the longest duration observed to date in mammals studied,” said lead author, RIKEN developmental biologist Wataru Kimura.
“If we could harness the molecular pathway that determines cardiac regeneration capacity, we should be able to develop novel therapeutic approaches to treat cardiovascular disease.”
Excitingly, they noted that the hearts of two-week-old opossums resembled those of day-old mice, and that the opossum’s heart muscle cells continued to divide for weeks after birth.
The researchers then looked for changes in gene expression that occurred in both opossum and mice, around the time when heart regeneration was no longer possible. The common factor was a protein called AMPK.
Further experiments showed that activation of AMPK in both mice and opossums appeared to stop cell division in the heart muscle.
When the team injected neonatal mice with AMPK inhibitors, the heart damage induced a week after birth was regenerated and the mice hearts regained normal function.
While this research is still extremely far from being used in humans, it is exciting for the research community.
“An important and exciting question is how neonatal marsupials maintain regenerative ability in extrauterine environments,” Kimura says. “The answers could lead to therapies that could induce heart regeneration in adults.”