Expression profile of the isogenic early mesodermal cells differentiated from induced pluripotent human stem cells

Abstract

Scar formation during normal regeneration of damaged tissue can lead to noticeable cosmetic and functional defects of organs and significantly affect the quality of life. However, it is known that fetal tissues before the third trimester of pregnancy are capable of complete regeneration with the restoration of the original architecture and functional activity. Understanding the cellular and molecular mechanisms of fetal wound regeneration will provide the basis for the development of successful treatments aimed to minimize scarring. Mesenchymal stromal cells (MSCs) play an important role in tissue repair, since the cytokines, chemokines, growth factors and extracellular vesicles they secrete are involved in the regulation of migration, angiogenesis, synthesis and remodeling of the extracellular matrix. Mesodermal differentiation of human induced pluripotent stem cells (iPSCs) makes possible to reproduce the successive stages of embryogenesis in vitro and to create isogenic cell models of MSCs corresponding to different stages of human development. In this work, we performed the directed multistage mesodermal differentiation of iPSCs into isogenic cell lines of the primitive streak, lateral and paraxial mesoderm and a comparative analysis of their expression profiles was carried out. It was shown that the resulting cells of the lateral mesoderm (LM) and paraxial mesoderm (PM) are precursors for MSCs. MSCs obtained as a result of differentiation of both LM and PM cells had a similar profile for the expression of pan-mesodermal markers. Comparative analysis of the functional activity of MSCs and their precursors in a pro-inflammatory microenvironment will provide molecular tools for a better understanding of the fundamental mechanisms of fetal tissue regeneration and identify therapeutic targets to minimize scarring and pathological processes characterized by excessive fibroplasia.