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Healing the heart
NEW YORK—Regenerative medicine--and by association, stem cells--has long been of significant interest to scientists, and some of the latest work out of the Icahn School of Medicine at Mount Sinai has identified a new promising contender: placental stem cells known as Cdx2 cells. In work that appeared in the Proceedings of the National Academy of Sciences, a research team found that these cells could help to regenerate heart cells in the wake of heart attack.
This work builds off of a previous discovery that a mixed population of mouse placental stem cells aided in the hearts' recovery in pregnant female mice that had suffered an injury that would otherwise result in heart failure. The stem cells were found to migrate to the site of the cart injury and program themselves as beating heart cells (cardiomyocytes). In this work, the Mount Sinai team sought to determine which specific cell types were driving this. Of the mixed population, Cdx2 were the most prevalent type, comprising 40 percent of the group.
“Cdx2 cells have historically been thought to only generate the placenta in early embryonic development, but never before were shown to have the ability to regenerate other organs, which is why this is so exciting. These findings may also pave the way to regenerative therapy of other organs besides the heart,” said principal investigator Dr. Hina Chaudhry, director of Cardiovascular Regenerative Medicine at the Icahn School of Medicine at Mount Sinai. “They almost seem like a super-charged population of stem cells, in that they can target the site of an injury and travel directly to the injury through the circulatory system and are able to avoid rejection by the host immune system.”
The research team induced heart attacks in three groups of male mice; of those, one group received Cdx2 stem cell treatments derived from end-gestation mouse placentas, one received placenta cells that did not express Cdx2, and one received a saline control. All mice were evaluated via MRI immediately after the heart attack and again three months after treatment. The mice in the non-Cdx2 and saline groups went into heart failure with no sign of cardiac regeneration, but the Cdx2 group showed significant improvement and regeneration of healthy tissue in heart—in fact, by three months, the stem cells had formed new blood vessels and cardiomyocytes.
This work also revealed that Cdx2 cells present with all the proteins of embryonic stem cells as well as additional proteins that allow them to travel to the site of injury. In addition, this subtype of stem cell seems to avoid triggering the host immune response, as none of the mice's immune systems rejected the transplants.
“These properties are critical to the development of a human stem cell treatment strategy, which we have embarked on, as this could be a promising therapy in humans. We have been able to isolate Cdx2 cells from term human placentas also; therefore, we are now hopeful that we can design a better human stem cell treatment for the heart than we have seen in the past,” Chaudhry noted. “Past strategies tested in humans were not based on stem cell types that were actually shown to form heart cells, and use of embryonic stem cells for this goal is associated with ethics and feasibility concerns. Placentas are routinely discarded around the world and thus almost a limitless source.”
A potential approach for treating heart damage is sorely needed. As noted in the PNAS article, “The regenerative capacity of the adult mammalian heart is very limited, and this contributes to the extensive morbidity and mortality associated with cardiovascular disease (1, 2). It has also become increasingly apparent that adult mammalian hearts do not harbor endogenous stem cells of any physiological relevance that can regenerate injured myocardium. Despite exhaustive investigations with multiple cell types over 15 y, cell therapy results for cardiac repair have thus far been marginal at best.”