Mesenchymal Stem Cells in Fibrotic Disease

Abstract

Fibrosis is associated with organ failure and high mortality and is commonly characterized by aberrant myofibroblast accumulation. Investigating the cellular origin of myofibroblasts in various diseases is thus a promising strategy for developing targeted anti-fibrotic treatments. Recent studies using genetic lineage tracing technology have implicated diverse organ-resident perivascular mesenchymal stem cell (MSC)-like cells and bone marrow-MSCs in myofibroblast generation during fibrosis development. In this Review, we give an overview of the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow.

Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

“…The persistent expansion and activation of tissue myofibroblasts is a salient feature of fibrosis and a major driver of disease progression [167]. Myofibroblasts are responsible for the deposition and maintenance of the fibrotic extracellular matrix (ECM) in all organs, which ultimately leads to deleterious tissue architectural changes and organ failure [168].…”

“…Myofibroblasts are responsible for the deposition and maintenance of the fibrotic extracellular matrix (ECM) in all organs, which ultimately leads to deleterious tissue architectural changes and organ failure [168]. Acute and chronic inflammation has been associated with uncontrolled responses to tissue injury, which leads to high concentration of both endocrine and paracrine factors that stimulate the trans-differentiation of organ resident precursor cells, such as fibroblasts or pericytes, into ECM-generating myofibroblasts [167,169]. It has also been proposed that myofibroblasts arise from mesenchymal stem cells that migrate from the bone barrow [170].…”

Immunohistochemical study of renal fibropoiesis associated with dogs naturally and experimentally infected with two different strains ofLeishmania(L.)infantum

“…This deposition can be so intense leading to the subversion of the tissue architecture and even hardening and retraction of the affected tissues and organs. Consequently, the organ reduces in size, undergoes deformation, and sometimes can be recognised macroscopically as nodules or streaks of white‐yellowish coloration on the surface and that deepen the cut . Fibroblasts are collagen‐producing mesenchymal cells that, once activated, differentiate into so‐called myofibroblasts.…”

“…So far, collagen production comes from myofibroblasts which can arise from many different cells of origin such as resident fibroblasts, mesenchymal stem cells (MSCs), pericytes, endothelial cells and bone marrow–derived monocytes (fibrocytes) . Another mechanism also described in the genesis of fibrosis is the mesenchymal‐epithelial transition (MET).…”

“…Consequently, the organ reduces in size, undergoes deformation, and sometimes can be recognised macroscopically as nodules or streaks of white-yellowish coloration on the surface and that deepen the cut. 34,35 Fibroblasts are collagen-producing mesenchymal cells that, once activated, differentiate into so-called myofibroblasts. According to Duffield, 36 the term myofibroblast derives from the mechanisms of wound healing in which these cells begin to express contractile intracytoplasmic molecules characteristic of smooth muscle cells such as smooth muscle alpha-actin, vimentin and desmin.…”