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Improvement of postnatal neovascularization by human embryonic stem cell derived endothelial-like cell transplantation in a mouse model of hindlimb ischemia

Cited 155 time in Web of Science Cited 171 time in Scopus
Authors
Moon, Sung-Hwan; Lee, Soo-Hong; Kang, Sun-Woong; Kim, Jumi; Lim, Jae Min; Kim, Hyo-Soo; Kim, Byung-Soo; Chung, Hyung-Min; Cho, Seung-Woo
Issue Date
2007-11-20
Publisher
American Heart Association
Citation
Circulation. 2007;116:2409-2419
Keywords
AnimalsAnimals, NewbornCell LineDisease Models, AnimalEmbryonic Stem Cells/*transplantationEndothelial Cells/*transplantationFemaleHindlimb/*blood supply/surgeryHumansIschemia/pathology/*physiopathology/*surgeryMiceMice, NudeNeovascularization, Physiologic/*physiologyStem Cell Transplantation/methods
Abstract
BACKGROUND: We established an efficient preparation method to obtain endothelial-like cells (ECs) from human embryonic stem cells (hESCs) and tested whether these hESC-ECs would show therapeutic potential for treatment of hindlimb ischemia. METHODS AND RESULTS: ECs differentiated from hESCs were obtained by mechanical isolation and cell sorting for von Willebrand factor. The isolated hESC-ECs maintained endothelial cell-specific characteristics such as endothelial marker expression and capillary formation. One day after surgical induction of hindlimb ischemia in athymic mice, hESC-ECs were injected intramuscularly into ischemic limbs. Four weeks after treatment, hESC-EC treatment significantly increased limb salvage (36%) compared with treatment with medium (0%). In addition, laser Doppler imaging showed that the ratio of blood perfusion (ischemic to normal limb) was increased significantly (P<0.01) by hESC-EC treatment (0.511+/-0.167) compared with medium injection (0.073+/-0.061). Capillary and arteriole densities were 658+/-190/mm2 and 30+/-11/mm2 in the hESC-EC group, respectively, whereas those in the medium group were 392+/-118/mm2 and 16+/-8/mm2, respectively (P<0.01). Reverse-transcription polymerase chain reaction with human-specific primers revealed mRNA expression of human endothelial markers and human angiogenic factors in ischemic mouse tissues. The transplanted hESC-ECs were localized as capillaries near muscle tissues in ischemic regions or incorporated in the vessels between muscle tissues, as confirmed by human nuclear antigen staining with platelet/endothelial cell adhesion molecule or von Willebrand factor. CONCLUSIONS: This study demonstrates that hESC-EC transplantation improves blood perfusion and limb salvage by facilitating postnatal neovascularization in a mouse model of hindlimb ischemia. Thus, hESC-ECs might be useful as an alternative cell source for angiogenic therapy.
ISSN
1524-4539 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17984381

http://hdl.handle.net/10371/28279
DOI
https://doi.org/10.1161/CIRCULATIONAHA.106.687038
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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