Back in 2011, researchers at the Icahn School of Medicine at Mount Sinai generated some excitement in the cardiology community when they announced they had used stem cells from placenta to regenerate damaged hearts in pregnant mice. Now, they’ve taken that research a step further, isolating the precise population of cells that have that regenerative ability.
The Mount Sinai team discovered that Cdx2 cells in the placenta of mice can migrate through the circulatory system and target heart injuries. Once there, the cells transform into beating heart cells and start the repair process. They published their findings in the journal Proceedings of the National Academy of Sciences.
The researchers knew from their previous study that a mixed population of placental stem cells could help repair injuries that would normally lead to heart failure in pregnant mice. They zeroed in on Cdx2 cells because they were the most prevalent cells in that mix and they comprised 40% of the cells that seemed to be promoting heart repair.
To confirm their hunch, they tested Cdx2 cells in three different mouse models of heart attack, all males: one group received the cells from mouse placentas, one got different placental cells and the rest were given a placebo. The researchers used MRI imaging to determine how the animals’ hearts were responding.
The Mount Sinai team observed that all of the mice in the Cdx2 group experienced regeneration of healthy heart tissue. Three months after the treatment, the stem cells had formed new blood vessels and beating heart muscle cells. There were no signs of regeneration in the other two groups.
Regenerating damaged heart muscle with stem cells is a popular pursuit among scientists targeting heart failure, but the results have been decidedly mixed so far. Last year, the NIH's National Heart, Lung, and Blood Institute pressed the pause button on a study of mesenchymal stem cells derived from bone marrow in patients with chronic heart failure after some prominent medical journals noted concerns about the veracity of past research related to cell therapy in cardiology.
Despite those concerns, BioCardia moved into a phase 3 trial of its bone-marrow-derived cell therapy in patients with heart failure after a heart attack. The company raised about $23 million to fund the trial. Australia-based Mesoblast is also working on a stem-cell based therapy for heart failure, but it turned in disappointing results from a phase 2 trial last year.
The Mount Sinai researchers believe Cdx2 placental cells offer several important advantages over other types of cells that have been studied in cardiovascular disorders. They not only express proteins that have the ability to generate all the organs in the body, they also have proteins that allow them to travel to injury sites. Plus, they don’t seem to cause a damaging immune response, they reported.
The team was able to isolate Cdx2 cells from full-term human placentas, too, raising the possibility of being able to harvest the treatment from an almost “limitless source” of placentas that would normally be discarded, said principal investigator Hina Chaudhry, M.D., director of cardiovascular regenerative medicine at the Icahn School, in a statement.
“These findings may also pave the way to regenerative therapy of other organs besides the heart,” Chaudhry added.