Article: Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells

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Publisher Website: 10.1002/dmrr.2304
Scopus: eid_2-s2.0-84863747424

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Title	Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells
Authors	Ho, JCY2 Lai, WH2 Li, MF2 Au, KW2 Yip, MC2 Wong, NLY2 Ng, ESK3 Lam, FFY3 Siu, CW1 2 Tse, HF1 2
Keywords	Conditioned Medium Diabetes Mellitus Endothelial Cells Human Embryonic Stem Cells
Issue Date	2012
Publisher	John Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394
Citation	Diabetes/Metabolism Research And Reviews, 2012, v. 28 n. 5, p. 462-473 [How to Cite?] DOI: http://dx.doi.org/10.1002/dmrr.2304
Abstract	Background: The potential clinical application of bone marrow or peripheral blood-derived progenitor cells for cardiovascular regeneration in patients with diabetes mellitus (DM) is limited by their functional impairment. We sought to determine the mechanisms of impaired therapeutic efficacy of peripheral blood-derived progenitor cells in type 2 DM patients and evaluated the use of cell-free conditioned medium obtained from human embryonic stem cell-derived endothelial-like cells (ESC-ECs) to reverse their functional impairment. Methods: The angiogenic potential of late outgrowth endothelial cells (OECs) and cytokine profile of the conditional medium of proangiogenic cells (PACs) derived from peripheral blood-mononuclear cells of healthy control and DM patients and ESC-ECs was compared by in vitro tube formation assay and a multiplex bead-based immunoassay kit, respectively. The in vivo angiogenic potential of ESC-ECs derived conditioned medium in rescuing the functional impairment of PB-PACs in DM patients was investigated using a hindlimb ischemia model. Results: Human ESC-ECs had similar functional and phenotypic characteristics as OECs in healthy controls. Cytokine profiling showed that vascular endothelial growth factor, stromal cell-derived factor 1 and placental growth factor were down-regulated in PACs from DM patients. Tube formation assay that revealed functional impairment of OECs from DM patients could be rescued by ESC-ECs conditioned medium. Administration of ESC-ECs conditioned medium restored the therapeutic efficacy of PB-PACs from DM patients in a mouse model of hindlimb ischemia. Conclusions: Our results showed that peripheral blood-derived progenitor cells from DM patients have impaired function because of defective secretion of angiogenic cytokines, which could be restored by supplementation of ESC-ECs conditioned medium. © 2012 John Wiley & Sons, Ltd.
ISSN	1520-7552 2011 Impact Factor: 3.373 2011 SCImago Journal Rankings: 0.274
DOI	http://dx.doi.org/10.1002/dmrr.2304
References	References in Scopus

DC Field	Value
dc.contributor.author	Ho, JCY
dc.contributor.author	Lai, WH
dc.contributor.author	Li, MF
dc.contributor.author	Au, KW
dc.contributor.author	Yip, MC
dc.contributor.author	Wong, NLY
dc.contributor.author	Ng, ESK
dc.contributor.author	Lam, FFY
dc.contributor.author	Siu, CW
dc.contributor.author	Tse, HF
dc.date.accessioned	2012-09-05T05:32:53Z
dc.date.available	2012-09-05T05:32:53Z
dc.date.issued	2012
dc.description.abstract	Background: The potential clinical application of bone marrow or peripheral blood-derived progenitor cells for cardiovascular regeneration in patients with diabetes mellitus (DM) is limited by their functional impairment. We sought to determine the mechanisms of impaired therapeutic efficacy of peripheral blood-derived progenitor cells in type 2 DM patients and evaluated the use of cell-free conditioned medium obtained from human embryonic stem cell-derived endothelial-like cells (ESC-ECs) to reverse their functional impairment. Methods: The angiogenic potential of late outgrowth endothelial cells (OECs) and cytokine profile of the conditional medium of proangiogenic cells (PACs) derived from peripheral blood-mononuclear cells of healthy control and DM patients and ESC-ECs was compared by in vitro tube formation assay and a multiplex bead-based immunoassay kit, respectively. The in vivo angiogenic potential of ESC-ECs derived conditioned medium in rescuing the functional impairment of PB-PACs in DM patients was investigated using a hindlimb ischemia model. Results: Human ESC-ECs had similar functional and phenotypic characteristics as OECs in healthy controls. Cytokine profiling showed that vascular endothelial growth factor, stromal cell-derived factor 1 and placental growth factor were down-regulated in PACs from DM patients. Tube formation assay that revealed functional impairment of OECs from DM patients could be rescued by ESC-ECs conditioned medium. Administration of ESC-ECs conditioned medium restored the therapeutic efficacy of PB-PACs from DM patients in a mouse model of hindlimb ischemia. Conclusions: Our results showed that peripheral blood-derived progenitor cells from DM patients have impaired function because of defective secretion of angiogenic cytokines, which could be restored by supplementation of ESC-ECs conditioned medium. © 2012 John Wiley & Sons, Ltd.
dc.description.nature	Link_to_subscribed_fulltext
dc.identifier.citation	Diabetes/Metabolism Research And Reviews, 2012, v. 28 n. 5, p. 462-473 [How to Cite?] DOI: http://dx.doi.org/10.1002/dmrr.2304
dc.identifier.doi	http://dx.doi.org/10.1002/dmrr.2304
dc.identifier.epage	473
dc.identifier.issn	1520-7552 2011 Impact Factor: 3.373 2011 SCImago Journal Rankings: 0.274
dc.identifier.issue	5
dc.identifier.scopus	eid_2-s2.0-84863747424
dc.identifier.spage	462
dc.identifier.uri	http://hdl.handle.net/10722/163514
dc.identifier.volume	28
dc.language	eng
dc.publisher	John Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394
dc.publisher.place	United Kingdom
dc.relation.ispartof	Diabetes/Metabolism Research and Reviews
dc.relation.references	References in Scopus
dc.subject	Conditioned Medium
dc.subject	Diabetes Mellitus
dc.subject	Endothelial Cells
dc.subject	Human Embryonic Stem Cells
dc.title	Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells
dc.type	Article

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Author Affiliations

The University of Hong Kong Li Ka Shing Faculty of Medicine
The University of Hong Kong
Chinese University of Hong Kong

Article: Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells

The HKU Scholars Hub has contact details for these author(s).