TY - JOUR
T1 - Polymer-DNA nanoparticle-induced CXCR4 overexpression improves stem cell engraftment and tissue regeneration in a mouse hindlimb ischemia model
AU - Deveza, Lorenzo
AU - Choi, Jeffrey
AU - Lee, Jerry
AU - Huang, Ngan
AU - Cooke, John
AU - Yang, Fan
N1 - 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.
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:
© Ivyspring International Publisher.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - CXCR4
UR - http://www.scopus.com/inward/record.url?scp=85024124421&partnerID=8YFLogxK
U2 - 10.7150/THNO.12866
DO - 10.7150/THNO.12866
M3 - Article
C2 - 27279910
AN - SCOPUS:85024124421
VL - 6
SP - 1176
EP - 1189
JO - Theranostics
JF - Theranostics
SN - 1838-7640
IS - 8
ER -