Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation.
Abstract
RATIONALE
Fetal cells enter the maternal circulation during pregnancy and may persist in maternal tissue for decades as microchimeras.
OBJECTIVE
Based on clinical observations of peripartum cardiomyopathy patients and the high rate of recovery they experience from heart
failure, our objective was to determine whether fetal cells can migrate to the maternal heart and differentiate to cardiac
cells.
METHODS AND RESULTS
We report that fetal cells selectively home to injured maternal hearts and undergo differentiation into diverse cardiac lineages.
Using enhanced green fluorescent protein (eGFP)-tagged fetuses, we demonstrate engraftment of multipotent fetal cells in injury
zones of maternal hearts. In vivo, eGFP+ fetal cells form endothelial cells, smooth muscle cells, and cardiomyocytes. In vitro,
fetal cells isolated from maternal hearts recapitulate these differentiation pathways, additionally forming vascular tubes
and beating cardiomyocytes in a fusion-independent manner; ≈40% of fetal cells in the maternal heart express Caudal-related
homeobox2 (Cdx2), previously associated with trophoblast stem cells, thought to solely form placenta.
CONCLUSIONS
Fetal maternal stem cell transfer appears to be a critical mechanism in the maternal response to cardiac injury. Furthermore,
we have identified Cdx2 cells as a novel cell type for potential use in cardiovascular regenerative therapy.
Links
Authors
Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, Altman P, Shachter NS, Nakano A, Najfeld V, Chaudhry HW
Institution
Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1030, New York, NY 10029, USA.
Source
Circulation research 110:1 2012 Jan 6 pg 82-93MeSH
AnimalsCell Differentiation
Cell Movement
Cells, Cultured
Endothelium, Vascular
Female
Fetal Stem Cells
Green Fluorescent Proteins
Homeodomain Proteins
Male
Maternal-Fetal Exchange
Mice
Mice, Inbred Strains
Mice, Transgenic
Models, Animal
Muscle, Smooth, Vascular
Myocardial Infarction
Myocardium
Myocytes, Cardiac
Pregnancy
Pregnancy Complications, Cardiovascular
Transcription Factors
Pub Type(s)
In VitroJournal Article
Research Support, N.I.H., Extramural
Language
eng
PubMed ID
22082491
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