Published Online
on March 15, 2004

A more recent version of this article appeared on March 23, 2004

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Submitted on June 26, 2003
Revised on December 15, 2003
Accepted on December 23, 2003

Human Mesenchymal Stem Cells Form Purkinje Fibers in Fetal Sheep Heart

Judith A. Airey PhD^*, Graça Almeida-Porada MD, PhD, Evan J. Colletti BS, Christopher D. Porada PhD, Jason Chamberlain BS, Matthew Movsesian MD, John L. Sutko PhD, and Esmail D. Zanjani PhD

From the Departments of Pharmacology (J.A.A., E.J.C., J.L.S.) and Animal Biotechnology (G.A.-P., C.D.P., J.C., E.D.Z.), University of Nevada, Reno; Specialty Care (Cardiology), VA Salt Lake City Health Care System; and Departments of Internal Medicine (Cardiology) and Pharmacology, University of Utah School of Medicine, Salt Lake City (M.M.).

^* To whom correspondence should be addressed. E-mail: jaairey{at}med.unr.edu.

Background--We have investigated the usefulness of a model of cardiac development in a large mammal, sheep, for studies of engraftment of human stem cells in the heart.

Methods and Results--Adult and fetal human mesenchymal stem cells were injected intraperitoneally into sheep fetuses in utero. Hearts at late fetal development were analyzed for engraftment of human cells. The majority of the engrafted cells of human origin formed segments of Purkinje fibers containing exclusively human cells. There were no differences in engraftment of human mesenchymal stem cells from adult bone marrow, fetal brain, and fetal liver. On average, 43.2% of the total Purkinje fibers in random areas (n=11) of both ventricles were of human origin. In contrast, 0.01% of cardiomyocytes were of human origin.

Conclusions--Human mesenchymal stem cells preferentially engraft at high levels in the ventricular conduction system during fetal development in sheep. These findings raise the possibility that stem cells contribute to normal development of the fetal heart.

Key words: stem cells • embryology • Purkinje fibers

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