Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction

Rafeeq Ph Ahmed, Muhammad Ashraf, Stephanie Buccini, Jiang Shujia, Husnain Kh Haider

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Aim: Genetic reprogramming of somatic cells with stemness genes to restore their pluripotent status is being studied extensively to generate pluripotent stem cells as an alternative to embryonic stem cells. This study was designed to examine the effectiveness of skeletal myoblast-derived induced pluripotent stem cells (SkiPS) from young male Oct4/GFP transgenic mice for regeneration of the infarcted heart. Methods & results: A mouse model of permanent coronary artery ligation was developed in young female immunocompetent C57BL/6J or C57BL/6x129S4 SV/jae Oct4/GFP mice. SkiPS labeled with Q-dots (3 × 10 5 in 10 μl basal Dulbecco's modified Eagle's medium) were transplanted in and around the area of infarct immediately after coronary artery ligation (n = 16) under direct vision. Control mice (n = 12) were injected with the same number of skeletal myoblasts. Histological studies documented successful engraftment of SkiPS in all the surviving animals 4 weeks later. However, six of the 16 SkiPS-transplanted (37.5%) animal hearts showed intramural teratomas, whereas no tumor growth was observed in the control mice. Q-dot-labeled donor cells were also observed at the site of tumors. Histological studies revealed that teratomas were composed of cells from all of the three embryonic germ layers. Ultra-structure studies confirmed the histological findings and showed regions with well-organized myofibrillar structures in the tumors. Conclusion: Undifferentiated induced pluripotent stem cells should not be recommended for cardiac transplantation unless screened for specific teratogenic precursors or predifferentiated into cardiac lineage prior to transplantation.

Original languageEnglish (US)
Pages (from-to)171-178
Number of pages8
JournalRegenerative Medicine
Volume6
Issue number2
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Myocardial Infarction
Skeletal Myoblasts
Tumors
Teratoma
Ligation
Coronary Vessels
Animals
Germ Layers
Neoplasms
Pluripotent Stem Cells
Eagles
Heart Transplantation
Embryonic Stem Cells
Transgenic Mice
Regeneration
Genes
Transplantation
Growth

Keywords

  • induced pluripotent stem cells
  • infarction
  • myoblast
  • tumor

ASJC Scopus subject areas

  • Biomedical Engineering
  • Embryology

Cite this

Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. / Ahmed, Rafeeq Ph; Ashraf, Muhammad; Buccini, Stephanie; Shujia, Jiang; Haider, Husnain Kh.

In: Regenerative Medicine, Vol. 6, No. 2, 01.03.2011, p. 171-178.

Research output: Contribution to journalArticle

Ahmed, Rafeeq Ph ; Ashraf, Muhammad ; Buccini, Stephanie ; Shujia, Jiang ; Haider, Husnain Kh. / Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. In: Regenerative Medicine. 2011 ; Vol. 6, No. 2. pp. 171-178.
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