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Organogenesis. 2020;16(1):14-26. doi: 10.1080/15476278.2019.1697597. Epub 2019 Dec 6.

Influence of Different Cell Types and Sources on Pre-Vascularisation in Fibrin and Agarose-Collagen Gels.

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Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany.
Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Geleen, The Netherlands.
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany.


Vascularisation is essential for the development of tailored, tissue-engineered organs and tissues due to diffusion limits of nutrients and the lack of the necessary connection to the cardiovascular system. To pre-vascularize, endothelial cells and supporting cells can be embedded in the scaffold to foster an adequate nutrient and oxygen supply after transplantation. This technique is applied for tissue engineering of various tissues, but there have been few studies on the use of different cell types or cells sources. We compare the effect of supporting cells from different sources on vascularisation. Fibrin gels and agarose-collagen hydrogels were used as scaffolds. The supporting cells were primary human dermal fibroblasts (HDFs), human nasal fibroblasts (HNFs), human mesenchymal stem cells from umbilical cord's Wharton's jelly (WJ MSCs), adipose-derived MSCs (AD MSCs) and femoral bone marrow-derived MSCs (BM MSCs). The tissue constructs were incubated for 14 days and analyzed by two-photon laser scanning microscopy. Vascularisation was supported by all cell types, forming branched networks of tubular vascular structures in both hydrogels. In general, fibrin gels present a higher angiogenic promoting environment compared to agarose-collagen hydrogels and fibroblasts show a high angiogenic potential in co-culture with endothelial cells. In agarose-collagen hydrogels, vascular structures supported by AD MSCs were comparable to our HDF control in terms of volume, area and length. BM MSCs formed a homogeneous network of smaller structures in both hydrogels. This study provides data toward understanding the pre-vascularisation properties of different supporting cell types and sources for tissue engineering of different organs and tissues.


3D cell culture; co-cultures; human mesenchymal stem cells; hydrogels; vascularisation

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