Expression Profile of Isogenic Early Mesodermal Cells Differentiated from Human Induced Pluripotent Stem Cells

Scar formation during normal regeneration of damaged tissuecan lead to noticeable cosmetic and functional defects of organsand thus significantly affect the quality of life. Meanwhile, fetaltissues before the third trimester of pregnancy are known to becapable of complete regeneration with the restoration of the originalarchitecture and functional activity. Understanding the cellularand molecular mechanisms of fetal wound regeneration will providethe basis for the development of successful treatments aimed to minimizescarring. Mesenchymal stromal cells (MSCs) play an important rolein tissue repair, since cytokines, chemokines, growth factors andextracellular vesicles they secrete are involved in the regulationof migration, angiogenesis, synthesis, and remodeling of the extracellularmatrix. Mesodermal differentiation of human induced pluripotentstem cells (iPSCs) enables to reproduce consecutive stages of embryogenesisin vitro and to create isogenic cell models of MSCs, correspondingto different stages of human development. Here, we performed a specificallydirected, multistage, mesodermal differentiation of iPSCs into isogeniccell lines of the primitive streak, lateral and paraxial mesoderm,as well as carried out a comparative analysis of their expressionprofiles. It was shown that the derived cells of the lateral mesoderm(LM) and paraxial mesoderm (PM) are precursors for MSCs. The MSCs,derived due to differentiation of both LM and PM cells, shared asimilar expression profile of pan-mesodermal markers. A comparativeanalysis of the functional activity of MSCs and their precursorsin a pro-inflammatory microenvironment will hopefully provide moleculartools for a better insight into the basic mechanisms of fetal tissueregeneration and help identify therapeutic targets to minimize scarringand pathological processes characterized by excessive fibroplasia.