@article{9997b6fe90a74844ae9cffaeea683ba3,
title = "Polymer-DNA nanoparticle-induced CXCR4 overexpression improves stem cell engraftment and tissue regeneration in a mouse hindlimb ischemia model",
abstract = "Peripheral arterial disease affects nearly 202 million individuals worldwide, sometimes leading to non-healing ulcers or limb amputations in severe cases. Genetically modified stem cells offer potential advantages for therapeutically inducing angiogenesis via augmented paracrine release mechanisms and tuned dynamic responses to environmental stimuli at disease sites. Here, we report the application of nanoparticle-induced CXCR4-overexpressing stem cells in a mouse hindlimb ischemia model. We found that CXCR4 overexpression improved stem cell survival, modulated inflammation in situ, and accelerated blood reperfusion. These effects, unexpectedly, led to complete limb salvage and skeletal muscle repair, markedly outperforming the efficacy of the conventional angiogenic factor control, VEGF. Importantly, assessment of CXCR4-overexpressing stem cells in vitro revealed that CXCR4 overexpression induced changes in paracrine signaling of stem cells, promoting a therapeutically desirable pro-angiogenic and anti-inflammatory phenotype. These results suggest that nanoparticle-induced CXCR4 overexpression may promote favorable phenotypic changes and therapeutic efficacy of stem cells in response to the ischemic environment.",
keywords = "CXCR4",
author = "Lorenzo Deveza and Jeffrey Choi and Jerry Lee and Ngan Huang and John Cooke and Fan Yang",
note = "Funding Information: The authors would like to thank the following funding sources for support including American Heart Association National Scientist Development Grant (10SDG2600001) (F.Y.), Stanford Chem-H Institute New Materials for Applications in Biology and Medicine Seed Grant (F.Y.), NIH R01DE024772-01 (F.Y.), NIH R01AR063717-01 (F.Y.), NIH R01AR055650-05A1 (F.Y.), National Science Foundation CAREER award program (CBET-1351289) (F.Y.), California Institute for Regenerative Medicine Tools and Technologies award ( RT3-07804) (F.Y.), Stanford Child Health Research Institute Faculty Scholar award (F.Y.), Stanford Bio-X Interdisciplinary program (F.Y.), and Alliance for Cancer Gene Therapy (F.Y.). L.D. would like to thank Stanford Medical Scientist Training Program for fellowship support. We thank Joseph Wu{\textquoteright}s lab at Stanford School of Medicine for kindly providing the GFP/luciferase transgenic mice for isolating cells. We thank Stanford Small Animal Imaging Facilities for support in bioluminescence imaging, and the Stanford Flow Cytometry Shared Resource for help with flow cytometry. Funding Information: The authors would like to thank the following funding sources for support including American Heart Association National Scientist Development Grant (10SDG2600001) (F.Y.), Stanford Chem-H Institute New Materials for Applications in Biology and Medicine Seed Grant (F.Y.), NIH R01DE024772-01 (F.Y.), NIH R01AR063717-01 (F.Y.), NIH R01AR055650-05A1 (F.Y.), National Science Foundation CAREER award program (CBET-1351289) (F.Y.), California Institute for Regenerative Medicine Tools and Technologies award (RT3-07804) (F.Y.), Stanford Child Health Research Institute Faculty Scholar award (F.Y.), Stanford Bio-X Interdisciplinary program (F.Y.), and Alliance for Cancer Gene Therapy (F.Y.). L.D. would like to thank Stanford Medical Scientist Training Program for fellowship support. We thank Joseph Wu's lab at Stanford School of Medicine for kindly providing the GFP/luciferase transgenic mice for isolating cells. We thank Stanford Small Animal Imaging Facilities for support in bioluminescence imaging, and the Stanford Flow Cytometry Shared Resource for help with flow cytometry. Publisher Copyright: {\textcopyright} Ivyspring International Publisher.",
year = "2016",
doi = "10.7150/THNO.12866",
language = "English (US)",
volume = "6",
pages = "1176--1189",
journal = "Theranostics",
issn = "1838-7640",
publisher = "Ivyspring International Publisher",
number = "8",
}