Angiogenic potential of endothelial progenitor cells and embryonic stem cells
Rae, Peter C., Kelly, Richard D. W., Egginton, Stuart and St. John, Justin C.. (2011) Angiogenic potential of endothelial progenitor cells and embryonic stem cells. Vascular Cell, Vol.3 (No.11). ISSN 2045-824X
WRAP_Kelly_2045-824X-3-11.pdf - Published Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://dx.doi.org/10.1186/2045-824X-3-11
Background: Endothelial 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).
Results: The 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.
Conclusions: We 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.
|Item Type:||Journal Article|
|Subjects:||Q Science > QP Physiology|
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Library of Congress Subject Headings (LCSH):||Stem cells, Reticulo-endothelial system, Neovascularization|
|Journal or Publication Title:||Vascular Cell|
|Publisher:||BioMed Central Ltd.|
|Official Date:||11 May 2011|
|Access rights to Published version:||Open Access|
|Funder:||Medical Research Council (Great Britain) (MRC)|
|Grant number:||GO600273 (MRC)|
1. Adams RH, Alitalo K: Molecular regulation of angiogenesis and
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