Marsupials are a quirky group of animals. They are one of three types of mammals, their defining feature is their young are born prematurely and the internal organs and cells of offspring continue to grow and divide for weeks after birth. Think a kangaroo joey growing inside a mother’s pouch.
A team of scientists from the RIKEN Centre for Biosystems Dynamics Research (BDR) in Japan has also found baby opossums have an extra trick up their tiny sleeves – they can regenerate their heart muscle for several weeks after birth.
And by tweaking a few choice genes, the researchers were able to repair a non-marsupial’s heart – mice – damaged a week after birth.
The team hope that their research – published in the journal Circulation – will be able to contribute to new regenerative heart medicine developments.
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 remains possible just after birth, but disappears quickly after a couple days.
“No mammalian species examined to date has been found capable of a meaningful regenerative response to myocardial injury later than one week after birth,” the team write in their new paper.
For humans and other mammals, damaged heart muscle – such as a heart attack – cannot be naturally repaired because matured heart-muscle cells do not regenerate.
The team hypothesised that in marsupials this might not be the case. Because marsupial’s hearts were still growing after birth – because their cells retained the ability to divide – this could allow the hearts to also regenerate after injury.
The researchers used the opossum (Monodelphis domestica) for the research, and they found that their hearts did in fact continue to grow for several weeks after birth.
When the team induced heart damage at two weeks, the heart repaired itself within a month, indicating that as long as heart cells continue to divide, the heart can be repaired.
“Cardiac regeneration for more than two weeks after birth in the opossum is the longest duration observed among mammals investigated to date,” says senior author, RIKEN developmental biologist Wataru Kimura.
“If we could exploit the molecular pathway that determines the capacity for cardiac regeneration, we should be able to establish novel therapeutic approaches for treating cardiovascular disease.”
Excitingly, they observed that the hearts of two-week-old opossums resembled those of one-day-old mice, and that opossum heart-muscle cells continued to divide for weeks after birth.
The researchers then looked for changes in gene expression which occurred in both opossum and mice, around the time that 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 seemed to stop cell division in heart muscle.
When the team injected neo-natal mice with AMPK inhibitors, heart damage induced a week after birth was regenerated and the mice hearts regained normal function.
Although this research is still extremely far off being used in humans, it is exciting the research community.
“One important and exciting question is how neonatal marsupials retain regenerative capacity in extrauterine environments,” says Kimura. “The answers could lead to therapies that can induce heart regeneration in adults.”