title: Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells.
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.
authors: Department of Radiology, Stanford University School of Medicine, Stanford, California 94305-5454, USA.
authors: Andrew S
authors: AS
authors: Lee
authors: Dan
authors: D
authors: Xu
authors: Jordan R
authors: JR
authors: Plews
authors: Patricia K
authors: PK
authors: Nguyen
authors: Divya
authors: D
authors: Nag
authors: Jennifer K
authors: JK
authors: Lyons
authors: Leng
authors: L
authors: Han
authors: Shijun
authors: S
authors: Hu
authors: Feng
authors: F
authors: Lan
authors: Junwei
authors: J
authors: Liu
authors: Mei
authors: M
authors: Huang
authors: Kazim H
authors: KH
authors: Narsinh
authors: Charles T
authors: CT
authors: Long
authors: Patricia E
authors: PE
authors: de Almeida
authors: Benjamin
authors: B
authors: Levi
authors: Nigel
authors: N
authors: Kooreman
authors: Charles
authors: C
authors: Bangs
authors: Cholawat
authors: C
authors: Pacharinsak
authors: Fumiaki
authors: F
authors: Ikeno
authors: Alan C
authors: AC
authors: Yeung
authors: Sanjiv S
authors: SS
authors: Gambhir
authors: Robert C
authors: RC
authors: Robbins
authors: Michael T
authors: MT
authors: Longaker
authors: Joseph C
authors: JC
authors: Wu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017202:Myocardial Ischemia / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous