IN VITRO ESTABLISHMENT OF VASCULARISED SKIN AND ORAL MUCOSA FROM HUMAN EMBRYONIC STEM CELLS FOR PRE-CLINICAL STUDIES AND INDUSTRIAL APPLICATIONS

Abstract

Skin and oral mucosal linings serve as the barrier between deeper tissues and external environment, and hence protects against various mechanical, chemical and biological insults. Development of three dimensional (3D) in vitro skin and mucosa tissue equivalents is a key step in the field of drug discovery and bio-pharmaceutical applications. Current models, which use monolayer cultures of primary cells, immortalized cell lines and/or animal models have yielded valuable insights to understand the biology and pathophysiology of skin. However, existing models have their own limitations such as, tissue relevance, longevity of functional tissues and multiple source of the cells involved. Hereby, we aimed to develop in vitro 3D skin and oral mucosa along with dermal component embedded with functional network of blood vessels. Fabrication of such complex tissue equivalents requires the multi-culture of appropriate cell types that include skin or oral mucosal keratinocytes (KCs), fibroblasts (Fib), endothelial cells (ECs) and vascular smooth muscle cells (vSMCs). We used human embryonic stem cells (hESCs) as the single cell source for the subsequent derivation of all the desired cell types needed for fabrication of in vitro skin and oral mucosa tissue equivalents.