A new type of cell discovered in human placentas could potentially be injected into the bloodstreams of people who have had heart attacks to help repair the damage.
at the Icahn School of Medicine at Mount Sinai in New York began investigating the potential heart-healing properties of placental cells after seeing two people spontaneously recover from heart failure while they were pregnant. She wondered if this effect was somehow mediated by their fetuses.
In an initial exploratory study, Chaudhry and her colleagues found that when they damaged the hearts of pregnant mice, cells from their placentas travelled to the site of injury and repaired the tissue, with these cells typically expressing a protein called CDX2.
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In 2019, the same researchers showed they could by injecting CDX2-expressing placental cells into their tail veins. “The cells appeared to have natural homing abilities,” says Chaudhry. “They were able to traverse through the circulation to the site of injury.” When the cells reached the damaged hearts, they transformed into beating heart cells and blood vessels that helped to regenerate the tissue.
Now, Chaudhry and , also at the Icahn School of Medicine at Mount Sinai, and their colleagues have discovered similar CDX2-expressing cells in the placentas of 106 women who donated them after giving birth. In petri-dish experiments, they found these cells could turn into beating heart cells and cells that form blood vessels, hinting that they may also be able to repair damaged hearts in people.
An advantage of the cells is that they appear to evade detection by the immune system, according to studies in mice and analysis of their gene expressions. This is probably because “when a baby and placenta are forming, they need to be tolerated by the mother’s immune system”, says Chaudhry. This means the cells shouldn’t be rejected by recipients’ bodies, she says.
Another bonus is that placental cells are easy to obtain because most placentas are discarded after birth, she says.
It is unclear why placentas contain these CDX2-expressing cells, but Chaudhry believes they may have evolved so that fetal cells in the placenta can repair maternal tissue damage that occurs during pregnancy. “The baby has to protect its home,” she says. The cells may also fix damage in other organs besides the heart, but that is yet to be explored, she says.
Other cell therapies that have previously been developed to try to regenerate damaged hearts have largely been disappointing. These have mostly involved stem cells, which have the potential to transform into heart cells at the site of injury. Fully formed adult heart cells aren’t suitable for injection since they are likely to provoke an immune reaction.
The stem cells evaluated in clinical trials so far have either lacked the homing abilities to reach the damaged heart or have failed to turn into heart cells once they get there, says Chaudhry. “We’re hoping the placental cells will overcome these issues,” she says.
at the University of Sydney, Australia, says the placental CDX2-expressing cells will need to be evaluated in larger animals to confirm that they do indeed find their way to damaged heart tissue and have regenerative properties. “I think there’s still a lot of maybes,” he says.
Chaudhry says her team is now planning to test the cells in pigs before hopefully progressing to clinical trials in people.
bioRxiv
