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Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell‐derived endothelial cells
Author(s) -
Ho Jenny C. Y.,
Lai WingHon,
Li MingFang,
Au KaWing,
Yip MeiChu,
Wong Navy L. Y.,
Ng Ethel S. K.,
Lam Francis F. Y.,
Siu ChungWah,
Tse HungFat
Publication year - 2012
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2304
Subject(s) - progenitor cell , stromal cell , embryonic stem cell , endothelial stem cell , peripheral blood mononuclear cell , stem cell , cytokine , medicine , bone marrow , immunology , angiogenesis , pathology , microbiology and biotechnology , biology , in vitro , biochemistry , gene
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. Copyright © 2012 John Wiley & Sons, Ltd.