The use of adipose mesenchymal stem cells and human umbilical vascular enothelial cells on a fibrin matrix for endothelialized skin substitutes
Authors
Isabel Sánchez-Muñoz, Rosario Granados, Purificación Holguín Holgado, José Antonio García-Vela, Celia Casares, Miguel Casares
Institution
Universitario de Getafe, Madrid, Spain
Country
Spain
Year
0000
Journal
Tissue Engineering
Abstract
In recent years, the reconstruction of human skin by tissue engineering represents a clinical challenge and has offered a therapeutic alternative. Avascular engineered skin equivalents have been available for several years and used to treat wounds due to burns, non-healing ulcers and surgical excisions. They are constituted by different types of cultured cells included in a three-dimensional structure that permits cellular proliferation to create tissue substitutes. The major drawback of this artificial skin substitutes is their lack of blood supply, since the endurance and cell proliferation of the substitute depend on an adequate oxygen and nutrients supply and on toxins removal. These functions are served by the vascular system. We have produced a new model of endothelialized skin substitute that promotes the formation of capillary-like structures by seeding human umbilical vein endothelial cells (HUVECs) with dermal fibroblasts and adipose derived mesenchymal stem cells (hADMSCs) in a fibrin matrix. Dermal fibroblasts and hADMSCs produce extracellular matrix that stimulates cellular growth and proliferation. hADMSCs secrete significant quantities of angiogenic and antiapoptotic factors (VEGF, HGF), which induce in vitro differentiation of these cells into endothelial cells promoting angiogenesis and participating in tissue repair and skin regeneration processes. We obtained the artificial skin substitute with similar structure to native skin, including dermis and epidermis. We demonstrated that endothelial cells (CD31 - and von Willebrand factor - positive) proliferated and organized themselves into capillary-like structures within the fibrin matrix. The epidermis showed a complete epithelization by squamous cells (AE1/AE3 cytokeratin positive) with intracytoplasmic keratohyalin granules, hyperkeratosis and parakeratosis.
Page 3 of 33 Tissue Engineering Part A
ADIPOSE MESENCHYMAL STEM CELLS AND HUMAN UMBILICAL VASCULAR ENDOTHELIAL CELLS ON A FIBRIN MATRIX FOR ENDOTHELIALIZED SKIN SUBSTITUTE (doi: 10.1089/This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
We have established a novel artificial skin substitute that facilitates the formation of capillary-like structures which may provide a novel therapeutic approach to different skin defects and prove to be a useful tool for regenerative medicine.