“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. 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.” says Hina Chaudhry, MD.
A mixed population of mouse placental cells was previous discovered to help the hearts of pregnant mice recover after an injury to the heart that could have otherwise lead to heart failure; placental stems cells were shown to have migrated to the mother’s heart from the placenta and directly to the site of the heart injury where they programmed themselves as beating heart cells to assist in repair processes.
To determine what type of stem cells made the hearts regenerate the researchers investigated Cdx2 cells which were the most prevalent type identified in the mixed population, they were found to comprise of 40% of those assisting the heart from the placenta. To test regenerative properties heart attacks were induced in 3 groups of male mice: one group received Cdx2 stem cell treatments derived from end gestation mouse placentas; another received placenta cells that did not express Cdx2; and the third group was a control group receiving saline.
All animals in the Dcx2 group were found to have had significant improvement and regeneration of healthy tissues in the heart; at 3 months stem cells had migrated directly to the heart injury and formed new cardiomyocytes and blood vessels, while the other 2 groups went into heart failure and had no evidence of regeneration.
Two other properties of the Cdx2 cells were noted: the immune system did not reject the cells when administered from placenta to another animal; and these cells have all the proteins of embryonic stem cells as well as additional proteins enabling them to travel directly to the injury sites which appear to avoid host immune responses.
“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. 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.” explains Chaudry.
“These results were very surprising to us, as no other cell type tested in clinical trials of human heart disease were ever shown to become beating heart cells in petri dishes, but these did and they knew exactly where to go when we injected them into the circulation,” adds Sangeetha Vadakke-Madathil, Ph.D.
