Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-...

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Autores principales:	Wing-Hon Lai, Jenny C Y Ho, Yau-Chi Chan, Joyce H L Ng, Ka-Wing Au, Lai-Yung Wong, Chung-Wah Siu, Hung-Fat Tse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0178d1874bb6403b8dadea718796450e
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spelling	oai:doaj.org-article:0178d1874bb6403b8dadea718796450e2021-11-18T07:54:54ZAttenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.1932-620310.1371/journal.pone.0057876https://doaj.org/article/0178d1874bb6403b8dadea718796450e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472116/?tool=EBIhttps://doaj.org/toc/1932-6203Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment of tissue ischemia.Wing-Hon LaiJenny C Y HoYau-Chi ChanJoyce H L NgKa-Wing AuLai-Yung WongChung-Wah SiuHung-Fat TsePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e57876 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wing-Hon Lai Jenny C Y Ho Yau-Chi Chan Joyce H L Ng Ka-Wing Au Lai-Yung Wong Chung-Wah Siu Hung-Fat Tse Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
description	Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment of tissue ischemia.
format	article
author	Wing-Hon Lai Jenny C Y Ho Yau-Chi Chan Joyce H L Ng Ka-Wing Au Lai-Yung Wong Chung-Wah Siu Hung-Fat Tse
author_facet	Wing-Hon Lai Jenny C Y Ho Yau-Chi Chan Joyce H L Ng Ka-Wing Au Lai-Yung Wong Chung-Wah Siu Hung-Fat Tse
author_sort	Wing-Hon Lai
title	Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
title_short	Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
title_full	Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
title_fullStr	Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
title_full_unstemmed	Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
title_sort	attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0178d1874bb6403b8dadea718796450e
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Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

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