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Endothelial Cells Derived From Human iPSCS Increase Capillary Density and Improve Perfusion in a Mouse Model of Peripheral Arterial Disease

Open access
Rufaihah, Abdul Jalil, Huang, Ngan F., Jamé, Sina, Lee, Jerry C., Nguyen, Ha N., Byers, Blake, De, Abhijit, Okogbaa, Janet, Rollins, Mark, Reijo-Pera, Renee, Gambhir, Sanjiv S., Cooke, John P.·2011·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract

Objective—: Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease. Methods and Results—: Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and vascular endothelial growth factor. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144, and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging and green fluorescence protein for fluorescent detection. The hiPSC-ECs (5×10 5 ) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). Bioluminescence imaging showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 versus 0.44±0.04; P =0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284±155 versus 797±206 capillaries/mm 2 ) ( P <0.002). Conclusion—: This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs.

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Metadata

Authors
Rufaihah, A. J., Huang, N. F., Jamé, S., Lee, J. C., Nguyen, H. N., Byers, B., De, A., Okogbaa, J., Rollins, M., Reijo-Pera, R., Gambhir, S. S., & Cooke, J. P.
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2011-11
Volume
31
Issue
11
Pages
e72-9
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W2107719420
Cited by
263
References
51
FWCI
7.99
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Endothelial Cells Derived From Human iPSCS Increase Capillary Density and Improve Perfusion in a Mouse Model of Peripheral Arterial Disease. https://app.cochat.ai/papers/10.1161/atvbaha.111.230938
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Rufaihah, A. J., Huang, N. F., Jamé, S., Lee, J. C., Nguyen, H. N., Byers, B., De, A., Okogbaa, J., Rollins, M., Reijo-Pera, R., Gambhir, S. S., & Cooke, J. P. (2011). Endothelial Cells Derived From Human iPSCS Increase Capillary Density and Improve Perfusion in a Mouse Model of Peripheral Arterial Disease. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/atvbaha.111.230938

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.