@misc{10481/70874,
year = {2021},
month = {9},
url = {http://hdl.handle.net/10481/70874},
abstract = {Objective: The aim of this study was to generate novel models of bioartificial human
oral mucosa with increased vascularization potential for future use as an advanced
therapies medicinal product, by using different vascular and mesenchymal stem cell
sources.
Background: Oral mucosa substitutes could contribute to the clinical treatment of
complex diseases affecting the oral cavity. Although several models of artificial oral
mucosa have been described, biointegration is a major issue that could be favored
by the generation of novel substitutes with increased vascularization potential once
grafted in vivo.
Methods: Three types of mesenchymal stem cells (MSCs) were obtained from adipose
tissue, bone marrow, and dental pulp, and their in vitro potential was evaluated by
inducing differentiation to the endothelial lineage using conditioning media. Then, 3D
models of human artificial oral mucosa were generated using biocompatible fibrin-agarose
biomaterials combined with human oral mucosa fibroblasts and each type
of MSC before and after induction to the endothelial lineage, using human umbilical
vein endothelial cells (HUVEC) as controls. The vascularization potential of each oral
mucosa substitute was assessed in vitro and in vivo in nude mice.
Results: In vitro induction of MSCs kept in culture was able to increase the expression
of VEGF, CD31, and vWF endothelial markers, especially in bone marrow and
dental pulp-MSCs,
and numerous proteins with a role in vasculogenesis become overexpressed.
Then, in vivo grafting resulted in a significant increase in blood vessels
formation at the interface area between the graft and the host tissues, with significantly
positive expression of VEGF, CD31, vWF, and CD34 as compared to negative
controls, especially when pre-differentiated
MSCs derived from bone marrow and
dental pulp were used. In addition, a significantly higher number of cells committed to the endothelial lineage expressing the same endothelial markers were found within
the bioartificial tissue.
Conclusion: Our results suggest that the use of pre-differentiated
MSCs could contribute
to a rapid generation of a vascular network that may favor in vivo biointegration
of bioengineered human oral mucosa substitutes.},
organization = {Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III)	FIS PI18/331	
FIS PI21/00980	
FIS PI18/332	
ICI19/00024},
organization = {Junta de Andalucia	PI-0442-2019},
organization = {European Commission},
publisher = {Wiley-Blackwell Publishing},
keywords = {Mesenchymal stem cells},
keywords = {Oral mucosa},
keywords = {Tissue engineering},
keywords = {Vascularization},
title = {Generation of a novel model of bioengineered human oral mucosa with increased vascularization potential},
doi = {10.1111/jre.12927},
author = {Blanco Elices, Cristina and Chato Astrain, Jesús and Oyonarte Gómez, Salvador and Bermejo Casares, Fabiola and España López, Antonio and Fernández Valadés, Ricardo and Sánchez Quevedo, María Del Carmen and Alaminos Mingorance, Miguel and Martín Piedra, Miguel Ángel and Garzón Bello, Ingrid Johanna},
}