Angiogenic potential of endothelial progenitor cells and embryonic stem cellsReport as inadecuate

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Vascular Cell

, 3:11

First Online: 11 May 2011Received: 09 March 2011Accepted: 11 May 2011


BackgroundEndothelial progenitor cells EPCs are implicated in a range of pathological conditions, suggesting a natural therapeutic role for EPCs in angiogenesis. However, current angiogenic therapies involving EPC transplantation are inefficient due to rejection of donor EPCs. One solution is to derive an expanded population of EPCs from stem cells in vitro, to be re-introduced as a therapeutic transplant. To demonstrate the therapeutic potential of EPCs we performed in vitro transplantation of EPCs into endothelial cell EC tubules using a gel-based tubule formation assay. We also described the production of highly angiogenic EPC-comparable cells from pluripotent embryonic stem cells ESCs by direct differentiation using EC-conditioned medium ECCM.

ResultsThe effect on tubule complexity and longevity varied with transplantation quantity: significant effects were observed when tubules were transplanted with a quantity of EPCs equivalent to 50% of the number of ECs originally seeded on to the assay gel but not with 10% EPC transplantation. Gene expression of the endothelial markers VEGFR2, VE-cadherin and CD31, determined by qPCR, also changed dynamically during transplantation. ECCM-treated ESC-derived progenitor cells exhibited angiogenic potential, demonstrated by in vitro tubule formation, and endothelial-specific gene expression equivalent to natural EPCs.

ConclusionsWe concluded the effect of EPCs is cumulative and beneficial, relying on upregulation of the angiogenic activity of transplanted cells combined with an increase in proliferative cell number to produce significant effects upon transplantation. Furthermore, EPCs derived from ESCs may be developed for use as a rapidly-expandable alternative for angiogenic transplantation therapy.

List of abbreviationsAng-1angiopoietin-1

AFAlexa Fluor

ANOVAanalysis of variance

bFGFbasic fibroblast growth factor

BMbone marrow

Cyt Bcytochrome c oxidase

Dday of differentiation


DICdifferential interference contrast

DMEMDulbecco-s modified Eagle medium

DNAdeoxyribonucleic acid

EBembryoid body

ECendothelial cell

ECCMendothelial cell conditioned medium

EGFendothelial growth factor

EPCendothelial progenitor cell

ESCembryonic stem cell

FBSfetal bovine serum

HLAhuman leukocyte antigen


LIFleukemia inhibitory factor

MEFmurine embryonic fibroblast

Nnode type

NAnumerical aperture

Qdotquantum dot

qPCRquantitative real-time polymerase chain reaction

RNAribonucleic acid

VEGFvascular endothelial growth factor

VEGFR2vascular endothelial growth factor receptor 2

vWFvon Willebrand Factor.

Electronic supplementary materialThe online version of this article doi:10.1186-2045-824X-3-11 contains supplementary material, which is available to authorized users.

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Author: Peter C Rae - Richard DW Kelly - Stuart Egginton - Justin C St John


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