Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting

Lim, Sei Hien; Kim, Choong; Aref, Amir R.; Kamm, Roger D.; Raghunath, Michael

doi:10.1039/C3IB40082D

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting
Authors:	Lim, Sei Hien Kim, Choong Aref, Amir R. Kamm, Roger D. Raghunath, Michael
DOI:	10.1039/C3IB40082D
Published in:	Integrative Biology
Volume(Issue):	2013
Issue:	12
Page(s):	1474
Pages to:	1484
Issue Date:	2013
Publisher / Ed. Institution:	Oxford University Press
ISSN:	1757-9708 1757-9694
Language:	English
Subject (DDC):	570: Biology
Abstract:	Capillary sprouting, a key step of neoangiogenesis in wound healing and tumor growth, also represents a therapeutic target for tissue repair. It requires crosstalk between endothelial cells (EC) and other cell types. We studied this process in a microfluidic platform that allows EC to migrate out of a channel across a collagen gel up a gradient of factors produced by a collection of encapsulated fibroblasts. Introduction of a prolyl hydroxylase inhibitor (PHi), ciclopirox olamine (CPX) to stabilize hypoxia inducible factor 1α (HIF-1α) predominantly in fibroblasts induced capillary sprouting in EC, but the most complex tubular networks with true lumina formed after combining CPX with the lysophospholipid sphingosine 1-phosphate (S1P). The enhanced angiogenesis is a possible consequence of the generation of mutually stimulating factors as each cell type responded differently to the compounds. The combination of CPX and S1P induced secretion of vascular endothelial growth factor (VEGF) in fibroblast culture whereas the angiogenic monocyte chemoattractant protein (MCP)-1 was exclusively secreted by fibroblasts, but only in the presence of EC-conditioned medium. Antibody interference with fibroblast-produced VEGF and MCP-1 inhibited the sprouting response. These observations not only demonstrate the collaboration of EC and fibroblasts in inducing capillary sprouting but also suggest that the combination of CPX and S1P enhances angiogenesis and thus might be of therapeutic value for the pharmacological induction of tissue repair and regeneration.
URI:	https://digitalcollection.zhaw.ch/handle/11475/12183
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Lim, S. H., Kim, C., Aref, A. R., Kamm, R. D., & Raghunath, M. (2013). Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting. Integrative Biology, 2013(12), 1474–1484. https://doi.org/10.1039/C3IB40082D

Lim, S.H. et al. (2013) ‘Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting’, Integrative Biology, 2013(12), pp. 1474–1484. Available at: https://doi.org/10.1039/C3IB40082D.

S. H. Lim, C. Kim, A. R. Aref, R. D. Kamm, and M. Raghunath, “Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting,” Integrative Biology, vol. 2013, no. 12, pp. 1474–1484, 2013, doi: 10.1039/C3IB40082D.

LIM, Sei Hien, Choong KIM, Amir R. AREF, Roger D. KAMM und Michael RAGHUNATH, 2013. Complementary effects of prolyl hydroxylase inhibitors and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting. Integrative Biology. 2013. Bd. 2013, Nr. 12, S. 1474–1484. DOI 10.1039/C3IB40082D

Lim, Sei Hien, Choong Kim, Amir R. Aref, Roger D. Kamm, and Michael Raghunath. 2013. “Complementary Effects of Prolyl Hydroxylase Inhibitors and Sphingosine 1-Phosphate on Fibroblasts and Endothelial Cells in Driving Capillary Sprouting.” Integrative Biology 2013 (12): 1474–84. https://doi.org/10.1039/C3IB40082D.

Lim, Sei Hien, et al. “Complementary Effects of Prolyl Hydroxylase Inhibitors and Sphingosine 1-Phosphate on Fibroblasts and Endothelial Cells in Driving Capillary Sprouting.” Integrative Biology, vol. 2013, no. 12, 2013, pp. 1474–84, https://doi.org/10.1039/C3IB40082D.