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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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TitleReversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells
 
AuthorsHo, JCY2
Lai, WH2
Li, MF2
Au, KW2
Yip, MC2
Wong, NLY2
Ng, ESK3
Lam, FFY3
Siu, CW2 1
Tse, HF2 1
 
KeywordsConditioned Medium
Diabetes Mellitus
Endothelial Cells
Human Embryonic Stem Cells
 
Issue Date2012
 
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394
 
CitationDiabetes/Metabolism Research And Reviews, 2012, v. 28 n. 5, p. 462-473 [How to Cite?]
DOI: http://dx.doi.org/10.1002/dmrr.2304
 
AbstractBackground: 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.
 
ISSN1520-7552
2012 Impact Factor: 2.968
2012 SCImago Journal Rankings: 0.981
 
DOIhttp://dx.doi.org/10.1002/dmrr.2304
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorHo, JCY
 
dc.contributor.authorLai, WH
 
dc.contributor.authorLi, MF
 
dc.contributor.authorAu, KW
 
dc.contributor.authorYip, MC
 
dc.contributor.authorWong, NLY
 
dc.contributor.authorNg, ESK
 
dc.contributor.authorLam, FFY
 
dc.contributor.authorSiu, CW
 
dc.contributor.authorTse, HF
 
dc.date.accessioned2012-09-05T05:32:53Z
 
dc.date.available2012-09-05T05:32:53Z
 
dc.date.issued2012
 
dc.description.abstractBackground: 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.natureLink_to_subscribed_fulltext
 
dc.identifier.citationDiabetes/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.doihttp://dx.doi.org/10.1002/dmrr.2304
 
dc.identifier.epage473
 
dc.identifier.issn1520-7552
2012 Impact Factor: 2.968
2012 SCImago Journal Rankings: 0.981
 
dc.identifier.issue5
 
dc.identifier.pmid22492468
 
dc.identifier.scopuseid_2-s2.0-84863747424
 
dc.identifier.spage462
 
dc.identifier.urihttp://hdl.handle.net/10722/163514
 
dc.identifier.volume28
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofDiabetes/Metabolism Research and Reviews
 
dc.relation.referencesReferences in Scopus
 
dc.subjectConditioned Medium
 
dc.subjectDiabetes Mellitus
 
dc.subjectEndothelial Cells
 
dc.subjectHuman Embryonic Stem Cells
 
dc.titleReversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells
 
dc.typeArticle
 
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<contributor.author>Lai, WH</contributor.author>
<contributor.author>Li, MF</contributor.author>
<contributor.author>Au, KW</contributor.author>
<contributor.author>Yip, MC</contributor.author>
<contributor.author>Wong, NLY</contributor.author>
<contributor.author>Ng, ESK</contributor.author>
<contributor.author>Lam, FFY</contributor.author>
<contributor.author>Siu, CW</contributor.author>
<contributor.author>Tse, HF</contributor.author>
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<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. &#169; 2012 John Wiley &amp; Sons, Ltd.</description.abstract>
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<subject>Conditioned Medium</subject>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Chinese University of Hong Kong