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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Placental stem cells could be differentiated into functional cardiac cells

Researchers at the Icahn School of Medicine at Mount Sinai have demonstrated the potential of a specific class of placental stem cells, Cdx2 cells, in regenerating healthy heart cells after heart attacks in animal models.

The limited regenerative potential of adult mammalian hearts has prompted the need for developing cell-based therapies that can restore contractile function in heart disease.

In the article published in PNAS, Dr Hina Chaudhry and team at the Icahn School of Medicine at Mount Sinai have shown that intravenous delivery of placental Caudal-type homeobox-2 (Cdx2) cells resulted in homing and differentiation of these cells into functional cardiomyocytes and blood cells in damaged hearts.

A previous study from the group showed the regenerative potential of mixed fetal cells in regenerating injured maternal heart. In the present study, the team exploited this intrinsic mechanism and identified cdx2 cells in placenta as the cell type responsible for cardiac regeneration.

Using a lineage-tracing strategy by labeling Cdx2 cells using fluorescent markers in a mouse model of myocardial infarction, they observed that Cdx2 cells differentiated into spontaneously beating cardiomyocytes and vascular cells in vitro.

When these cells were administered via tail vein to infarcted wild-type male mice, they selectively localized to the heart and differentiated to cardiomyocytes and blood vessels.

The team also performed proteomics to identify the genes active in cdx-2 cells and results showed that in addition to having the “stem”-related functions of embryonic stem cells, cdx2 cells also exhibited genes that helped in homing and survival and evade immune response, which is crucial for cell-based therapies.
Findings from the study demonstrate Cdx2 cells’ ability to regenerate cardiac and vascular cells. If this holds true, it could be a promising therapy to embark on for cardiac repair.

Dr Sangeetha Vadakke-Madathil, first author and postdoctoral fellow in Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai commented: “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.”

Source: Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart. Vadakke-Madathil S et al., PNAS, May 2019. Website

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