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. 2006 Feb;22 Suppl B(Suppl B):66B-71B.
doi: 10.1016/s0828-282x(06)70989-8.

A novel approach to studying transformation of human stem cells into cardiac cells in vivo

Edward T H Yeh  1 , Sui Zhang
Affiliations

A novel approach to studying transformation of human stem cells into cardiac cells in vivo

Edward T H Yeh et al. Can J Cardiol. 2006 Feb.

Abstract
in English, French

Stem cell transplantation has been proposed as a novel means of regenerating new myocardium following cardiac damage. Many laboratories have demonstrated that stem cells from different sources have the potential to transform into cardiomyocytes. Human peripheral blood CD34+ cells were transplanted into the hearts of mice with severe combined immune deficiency syndrome, and it was demonstrated that human stem cells could transform into cardiomyocytes, endothelial cells and smooth muscle cells. Using single cell preparation, cell sorting and fluorescent in situ hybridization, human peripheral blood CD34+ cells were transformed into cardiomyocytes mainly through cell fusion, whereas endothelial cells were derived through direct differentiation of the transplanted stem cells. This analytical method should provide a novel approach to identifying the mechanisms of stem cell transformation into cardiomyocytes in vivo.

La greffe de cellules souches a été proposée comme démarche novatrice pour régénérer le myocarde après des dommages cardiaques. De nombreux laboratoires ont démontré que les cellules souches de diverses sources peuvent se transformer en cardiomyocytes. Des cellules CD34+ du sang périphérique humain ont été greffées dans le cœur de souris atteintes d’un syndrome d’immunodéficience combinée sévère, et il a été démontré que les cellules souches pouvaient se transformer en cardiomyocytes, en cellules endothéliales et en cellules des muscles lisses. À l’aide de préparations unicellulaires, de classement cellulaire et d’hybridation in situ en fluorescence, les cellules CD34+ du sang périphérique humain ont été transformées en cardiomyocytes, notamment par fusion cellulaire, tandis que les cellules endothéliales étaient dérivées par différenciation directe des cellules souches greffées. Cette méthode analytique devrait procurer une démarche novatrice pour repérer les mécanismes de transformation des cellules souches en cardiomyocytes in vivo.

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Figures

Figure 1)
Figure 1)
Adult human peripheral blood CD34+ cells transformed into cardiomyocytes in vivo A Antitroponin T; B Antihuman leukocyte antigen; C Overlay of A and B. Reprinted from reference with permission
Figure 2)
Figure 2)
Transformation of adult human blood CD34+ cells into vascular smooth muscle cells in a heart injured by experimental myocardial infarction. A Antihuman leukocyte antigen. B Antismooth muscle actin. C Overlay of A and B. D Higher magnification of C. Reprinted from reference with permission
Figure 3)
Figure 3)
Human peripheral blood CD34+ cells differentiate into vascular endothelial cells in the heart with experimental myocardial infarction. A Antihuman leukocyte antigen. B Antivascular endothelial cadherin. C Overlay of A and B. D Higher magnification of C. Reprinted from reference with permission
Figure 4)
Figure 4)
Adult blood CD34+ cells transformed into cells of cardiomyocyte morphology in myocardial infarction damaged hearts. A Antihuman leukocyte antigen. B Antitroponin T. C Overlay of A and B. D Higher magnification of C. Reprinted from reference with permission
Figure 5)
Figure 5)
Fluorescence-activated cell sorting (FACS) of cells isolated from the whole heart (injured) from severe combined immunodeficient mice with transplanted human peripheral blood CD34+ cells. A Human leukocyte antigen (HLA)+ cells determined by FACS analysis. B HLA and troponin T double-positive cells determined by FACS analysis. C Double-positive cells from a heart harvested 24 h after transplantation. D HLA and cardiac troponin T double-positive cells from a heart examined six months after transplantation. FITC Fluorescein isothiocyanate; Ig Immunoglobulin
Figure 6)
Figure 6)
Both fusion and transdifferentiation account for the transformation of CD34+ cells into cardiomyocytes in vivo. A Nuclei from troponin T+, human leukocyte antigen (HLA)– cells. B Nuclei from 70% of troponin T+, HLA+ cells. C Nuclei from 30% of troponin T+, HLA+ cells. Green areas: mouse X chromosome; Red areas: human X chromosome. Reprinted from reference with permission
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