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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

TitleReversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells
Authors
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
Citation
Diabetes/Metabolism Research And Reviews, 2012, v. 28 n. 5, p. 462-473 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/163514
ISSN
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHo, JCYen_US
dc.contributor.authorLai, WHen_US
dc.contributor.authorLi, MFen_US
dc.contributor.authorAu, KWen_US
dc.contributor.authorYip, MCen_US
dc.contributor.authorWong, NLYen_US
dc.contributor.authorNg, ESKen_US
dc.contributor.authorLam, FFYen_US
dc.contributor.authorSiu, CWen_US
dc.contributor.authorTse, HFen_US
dc.date.accessioned2012-09-05T05:32:53Z-
dc.date.available2012-09-05T05:32:53Z-
dc.date.issued2012en_US
dc.identifier.citationDiabetes/Metabolism Research And Reviews, 2012, v. 28 n. 5, p. 462-473en_US
dc.identifier.issn1520-7552en_US
dc.identifier.urihttp://hdl.handle.net/10722/163514-
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.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394en_US
dc.relation.ispartofDiabetes/Metabolism Research and Reviewsen_US
dc.subjectConditioned Mediumen_US
dc.subjectDiabetes Mellitusen_US
dc.subjectEndothelial Cellsen_US
dc.subjectHuman Embryonic Stem Cellsen_US
dc.titleReversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cellsen_US
dc.typeArticleen_US
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_US
dc.identifier.authorityTse, HF=rp00428en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/dmrr.2304en_US
dc.identifier.pmid22492468-
dc.identifier.scopuseid_2-s2.0-84863747424en_US
dc.identifier.hkuros240113-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863747424&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume28en_US
dc.identifier.issue5en_US
dc.identifier.spage462en_US
dc.identifier.epage473en_US
dc.identifier.isiWOS:000306127400012-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHo, JCY=7402650173en_US
dc.identifier.scopusauthoridLai, WH=18434390500en_US
dc.identifier.scopusauthoridLi, MF=26661782700en_US
dc.identifier.scopusauthoridAu, KW=9738204200en_US
dc.identifier.scopusauthoridYip, MC=36741863200en_US
dc.identifier.scopusauthoridWong, NLY=48663288500en_US
dc.identifier.scopusauthoridNg, ESK=55312374100en_US
dc.identifier.scopusauthoridLam, FFY=36783962600en_US
dc.identifier.scopusauthoridSiu, CW=55164929800en_US
dc.identifier.scopusauthoridTse, HF=7006070805en_US

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