Researchers at Mount Sinai Icahn School of Medicine have used a type of placental stem cell to successfully repair heart tissue following a heart attack in animal models.
The research follows on from a previous study in which the researchers demonstrated that a mixture of placental stem cells could repair heart tissue in female mice with a heart injury that would otherwise lead to heart failure. The study revealed the cells migrated to the heart where they differentiated into functional heart tissue at the site of injury.
In the latest study, the researchers analyzed which type of stem cell were responsible for the regeneration of heart tissue. In the previous study, the most common type of stem cell in the mix was Cdx2, which comprised 40% of the cells in the mixed population that travelled from the placenta to the heart through the blood stream.
To determine whether the stem cells were capable of repairing heart tissue, the researchers induced heart attacks in three groups of male mice. Once group received a saline solution as a control, a second group received placental cells that did not express Cdx2, and the third group received Cdx2 stem cell treatments from end-gestation mouse placentas.
MRI scans were conducted immediately after the mice had heart attacks and three months following treatment. After three months, the Cdx2 stem cells had all migrated to the heart and all mice in the Cdx2 group showed significant repair of the damaged heart tissue with the Cdx2 cells having differentiated into cardiomyocytes and blood vessels. There was no evidence of any regeneration of heart tissue in the other two groups of mice, which later went into heart failure.
As is the case with embryonic stem cells, all of the proteins are present to enable the cells to differentiate into any organ, so they have potential to be used to repair other injured organs. Crucially, and in contrast to embryonic stem cells, placental Cdx2 stem cells have additional proteins which enable them to move directly to the site of injury.
One problem with stem cell treatments is a potential immune response if stem cells are taken from a donor and are used to treat another individual. Cdx2 stem cells did not trigger an immune response when they were taken from the placenta of one animal and were used in another animal.
While previous studies have been conducted on humans using stem cells in an attempt to regenerate heart tissue, those studies have not used placental stem cells that have been shown to have the ability to repair heart tissue. Clinical trials using other types of stem cells have not resulted in the stem cells differentiating into fully functional beating heart cells. Further, in contrast to other types of stem cells, the Cdx2 cells know exactly where to go and migrate to the site of injury when they are injected into the blood stream.
The use of Cdx2 stem cells would also avoid the ethical problems associated with using embryonic stem cells. Placentas are discarded after birth which means there is a virtually limitless supply. The researchers have been able to extract Cdx2 stem cells from human placentas, so they could potentially be used in human stem cell treatments.
The findings have been published in the paper – Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart – which was recently published in the journal Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1811827116