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Promotion of Vascular Morphogenesis of Endothelial Cells Co-Cultured with Human Adipose-Derived Mesenchymal Stem Cells Using Polycaprolactone/Gelatin Nanofibrous Scaffolds

1
Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea
2
Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea
3
Advanced Institutes of Convergence Technology, Gyeonggi-do 16229, Korea
4
Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul 03080, Korea
5
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongman 13620, Korea
*
Authors to whom correspondence should be addressed.
Nanomaterials 2018, 8(2), 117; https://doi.org/10.3390/nano8020117
Received: 31 January 2018 / Revised: 10 February 2018 / Accepted: 13 February 2018 / Published: 18 February 2018
(This article belongs to the Special Issue The Fabrication and Application of Nanofibers)
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Abstract

New blood vessel formation is essential for tissue regeneration to deliver oxygen and nutrients and to maintain tissue metabolism. In the field of tissue engineering, in vitro fabrication of new artificial vessels has been a longstanding challenge. Here we developed a technique to reconstruct a microvascular system using a polycaprolactone (PCL)/gelatin nanofibrous structure and a co-culture system. Using a simple electrospinning process, we fabricated three-dimensional mesh scaffolds to support the sprouting of human umbilical vein endothelial cells (HUVECs) along the electrospun nanofiber. The co-culture with adipose-derived mesenchymal stem cells (ADSCs) supported greater sprouting of endothelial cells (ECs). In a two-dimensional culture system, angiogenic cell assembly produced more effective direct intercellular interactions and paracrine signaling from ADSCs to assist in the vascular formation of ECs, compared to the influence of growth factor. Although vascular endothelial growth factor and sphingosine-1-phosphate were present during the culture period, the presence of ADSCs was the most important factor for the construction of a cell-assembled structure in the two-dimensional culture system. On the contrary, HUVECs co-cultured on PCL/gelatin nanofiber scaffolds produced mature and functional microvessel and luminal structures with a greater expression of vascular markers, including platelet endothelial cell adhesion molecule-1 and podocalyxin. Furthermore, both angiogenic factors and cellular interactions with ADSCs through direct contact and paracrine molecules contributed to the formation of enhanced engineered blood vessel structures. It is expected that the co-culture system of HUVECs and ADSCs on bioengineered PCL/gelatin nanofibrous scaffolds will promote robust and functional microvessel structures and will be valuable for the regeneration of tissue with restored blood vessels. View Full-Text
Keywords: co-culture; endothelial cells; mesenchymal stem cells; electrospun nanofiber; angiogenesis co-culture; endothelial cells; mesenchymal stem cells; electrospun nanofiber; angiogenesis
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Kook, Y.-M.; Kim, H.; Kim, S.; Heo, C.Y.; Park, M.H.; Lee, K.; Koh, W.-G. Promotion of Vascular Morphogenesis of Endothelial Cells Co-Cultured with Human Adipose-Derived Mesenchymal Stem Cells Using Polycaprolactone/Gelatin Nanofibrous Scaffolds. Nanomaterials 2018, 8, 117.

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