Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells

Andrew S. Lee, Dan Xu, Jordan R. Plews, Patricia K. Nguyen, Divya Nag, Jennifer K. Lyons, Leng Han, Shijun Hu, Feng Lan, Junwei Liu, Mei Huang, Kazim H. Narsinh, Charles T. Long, Patricia E. De Almeida, Benjamin Levi, Nigel Kooreman, Charles Bangs, Cholawat Pacharinsak, Fumiaki Ikeno, Alan C. YeungSanjiv S. Gambhir, Robert C. Robbins, Michael T. Longaker, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.

Original languageEnglish (US)
Pages (from-to)32697-32704
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
StatePublished - Sep 16 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells'. Together they form a unique fingerprint.

Cite this