Administration of allogenic stem cells dosed to secure cardiogenesis and sustained infarct repair

Atta Behfar, Denice M. Hodgson, Leonid V. Zingman, Carmen M Terzic, Satsuki Yamada, Garvan M Kane, Alexey E. Alekseev, Michel Pucéat, Andre Terzic

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The mitotic capacity of heart muscle is too limited to fully substitute for cells lost following myocardial infarction. Emerging stem cell-based strategies have been proposed to overcome the self-renewal shortfall of native cardiomyocytes, yet there is limited evidence for their capability to achieve safe de novo cardiogenesis and repair. We present our recent experience in treating long-term, infarcted hearts with embryonic stem cells, a prototype source for allogenic cell therapy. The cardiogenic potential of the engrafted murine embryonic stem cell colony was pre-tested by in vitro differentiation, with derived cells positive for nuclear cardiac transcription factors, sarcomeric proteins and functional excitation-contraction coupling. Eight weeks after infarct, rats were randomized into sham- or embryonic stem cell-treated groups. A cellular sham controls or embryonic stem cells, engineered to express enhanced cyan fluorescent protein (ECFP) under control of the cardiac actin promoter, were injected through a 28-gauge needle at three sites into the peri-infarct zone for serial assessment of functional and structural impact. In contrast to results with sham-treated animals, stem cell therapy yielded, over the 5-month follow-up period, new ECFP-positive cardiomyocytes that integrated with the infarcted myocardium. The stem cell-treated group showed a stable contractile performance benefit with normalization of myocardial architecture post infarction. Transition of embryonic stem cells into cardiomyocytes required host signaling to support cardiac-specific differentiation and could result in tumorigenesis if the stem cell dose exceeded the heart's cardioinductive capacity. Supported by the host environment, proper dosing and administration of embryonic stem cells is thus here shown useful in the chronic management of cardiac injury promoting sustained repair.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1049
DOIs
StatePublished - 2005

Fingerprint

Embryonic Stem Cells
Stem cells
Repair
Stem Cells
Cardiac Myocytes
Cell- and Tissue-Based Therapy
Myocardium
Excitation Contraction Coupling
Infarction
Needles
Actins
Carcinogenesis
Transcription Factors
Myocardial Infarction
Wounds and Injuries
Gages
Muscle
Rats
Animals
Proteins

Keywords

  • Embryonic stem cells
  • Heart
  • Regeneration
  • Teratoma
  • Therapy
  • Tumor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Administration of allogenic stem cells dosed to secure cardiogenesis and sustained infarct repair. / Behfar, Atta; Hodgson, Denice M.; Zingman, Leonid V.; Terzic, Carmen M; Yamada, Satsuki; Kane, Garvan M; Alekseev, Alexey E.; Pucéat, Michel; Terzic, Andre.

In: Annals of the New York Academy of Sciences, Vol. 1049, 2005, p. 189-198.

Research output: Contribution to journalArticle

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