Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart

Circulation. 2004 Mar 23;109(11):1401-7. doi: 10.1161/01.CIR.0000124222.16321.26. Epub 2004 Mar 15.

Abstract

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, approximately 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.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Specificity
  • Cell Differentiation
  • Cell Lineage
  • Fetal Heart / anatomy & histology*
  • Gestational Age
  • Graft Survival
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / immunology
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Microscopy, Fluorescence
  • Models, Animal*
  • Molecular Chaperones
  • Myocytes, Cardiac / cytology
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / immunology
  • Purkinje Fibers / cytology*
  • Sheep / embryology
  • Transplantation Chimera
  • Transplantation, Heterologous

Substances

  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Neoplasm Proteins