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Tissue Eng Part A. 2016 Nov;22(21-22):1296-1304. Epub 2016 Oct 10.

The Influence of Platelet-Derived Growth Factor and Bone Morphogenetic Protein Presentation on Tubule Organization by Human Umbilical Vascular Endothelial Cells and Human Mesenchymal Stem Cells in Coculture.

Bayer EA1,2, Fedorchak MV1,2,3,4, Little SR1,2,3,5,6.

Author information

1
1 Department of Bioengineering, The University of Pittsburgh , Pittsburgh, Pennsylvania.
2
2 The McGowan Institute for Regenerative Medicine, The University of Pittsburgh , Pittsburgh, Pennsylvania.
3
3 Department of Chemical Engineering, The University of Pittsburgh , Pittsburgh, Pennsylvania.
4
4 Department of Ophthalmology, The University of Pittsburgh , Pittsburgh, Pennsylvania.
5
5 Department of Immunology, The University of Pittsburgh , Pittsburgh, Pennsylvania.
6
6 Department of Pharmaceutical Sciences, The University of Pittsburgh , Pittsburgh, Pennsylvania.

Abstract

A three-dimensional in vitro Matrigel plug was used as a model to explore delivery patterns of platelet-derived growth factor (PDGF) and bone morphogenetic protein-2 (BMP-2) to a coculture of human mesenchymal and endothelial cells. While BMP-2 is well recognized for its role in promoting fracture healing through proliferation and differentiation of osteoclast precursors, it is not a growth factor known to promote the process of angiogenesis, which is also critical for complete bone tissue repair. PDGF, in contrast, is a known regulator of angiogenesis, and also a powerful chemoattractant for osteoblast precursor cells. It has been suggested that presentation of PDGF followed by BMP may better promote vascularized bone tissue formation. Yet, it is unclear as to how cells would respond to various durations of delivery of each growth factor as well as to various amounts of overlap in presentation in terms of angiogenesis. Using a three-dimensional in vitro Matrigel plug model, we observed how various presentation schedules of PDGF and BMP-2 influenced tubule formation by human mesenchymal stem cells and human umbilical vascular endothelial cells. We observed that sequential presentation of PDGF to BMP-2 led to increased tubule formation over simultaneous delivery of these growth factors. Importantly, a 2-4 day overlap in the sequential presentation of PDGF and BMP-2 increased tubule formation as compared with groups with zero or complete growth factor overlap, suggesting that a moderate amount of angiogenic and osteogenic growth factor overlap may be beneficial for processes associated with angiogenesis.

KEYWORDS:

3D cell culture; angiogenesis; endothelial cells; growth factors; mesenchymal stem cells

PMID:
27650131
PMCID:
PMC5107722
DOI:
10.1089/ten.TEA.2016.0163
[Indexed for MEDLINE]
Free PMC Article

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