TY - JOUR
T1 - Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells
AU - Lee, Andrew S.
AU - Xu, Dan
AU - Plews, Jordan R.
AU - Nguyen, Patricia K.
AU - Nag, Divya
AU - Lyons, Jennifer K.
AU - Han, Leng
AU - Hu, Shijun
AU - Lan, Feng
AU - Liu, Junwei
AU - Huang, Mei
AU - Narsinh, Kazim H.
AU - Long, Charles T.
AU - De Almeida, Patricia E.
AU - Levi, Benjamin
AU - Kooreman, Nigel
AU - Bangs, Charles
AU - Pacharinsak, Cholawat
AU - Ikeno, Fumiaki
AU - Yeung, Alan C.
AU - Gambhir, Sanjiv S.
AU - Robbins, Robert C.
AU - Longaker, Michael T.
AU - Wu, Joseph C.
PY - 2011/9/16
Y1 - 2011/9/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052726674&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.235739
DO - 10.1074/jbc.M111.235739
M3 - Article
C2 - 21719696
AN - SCOPUS:80052726674
SN - 0021-9258
VL - 286
SP - 32697
EP - 32704
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -