Abstract
Perinatal cells, including cells from placenta, fetal annexes (amniotic and chorionic membranes), umbilical cord, and amniotic fluid display intrinsic immunological properties which very likely contribute to the development and growth of a semiallogeneic fetus during pregnancy. Many studies have shown that perinatal cells can inhibit the activation and modulate the functions of various inflammatory cells of the innate and adaptive immune systems, including macrophages, neutrophils, natural killer cells, dendritic cells, and T and B lymphocytes. These immunological properties, along with their easy availability and lack of ethical concerns, make perinatal cells very useful/promising in regenerative medicine. In recent years, extracellular vesicles (EVs) have gained great interest as a new therapeutic tool in regenerative medicine being a cell-free product potentially capable, thanks to the growth factors, miRNA and other bioactive molecules they convey, of modulating the inflammatory microenvironment thus favoring tissue regeneration. The immunomodulatory actions of perinatal cells have been suggested to be mediated by still not fully identified factors (secretoma) secreted either as soluble proteins/cytokines or entrapped in EVs. In this review, we will discuss how perinatal derived EVs may contribute toward the modulation of the immune response in various inflammatory pathologies (acute and chronic) by directly targeting different elements of the inflammatory microenvironment, ultimately leading to the repair and regeneration of damaged tissues.
Highlights
Anna Cargnoni1†, Andrea Papait1,2†, Alice Masserdotti2, Anna Pasotti1, Francesca Romana Stefani1, Antonietta Rosa Silini1* and Ornella Parolini2,3
IV injection of extracellular vesicles (EVs) and exosomes from hUC-mesenchymal stromal cells (MSC) was able to reduce inflammatory cytokines and induce M2 macrophage polarization with a concomitant improvement of motor function in models of spinal cord injury induced in mice (Sun et al, 2018) and in rats (Romanelli et al, 2019), respectively
This effect was due to the reduction of MCP1, TNF-α, and ICAM1. These findings were confirmed in in vitro experiments where the treatment with UC-MSC EVs was able to reduce the expression of MCP1 positively impacting the amount of heat-induced apoptosis or death of retinal cells (Yu et al, 2016). These findings suggested that UC-MSC EVs exert their protective effect, at least partially, through regulation of MCP-1 and macrophage infiltration
Summary
Anna Cargnoni1†, Andrea Papait1,2†, Alice Masserdotti2, Anna Pasotti1, Francesca Romana Stefani1, Antonietta Rosa Silini1* and Ornella Parolini2,3. IV injection of EVs and exosomes from hUC-MSCs was able to reduce inflammatory cytokines and induce M2 macrophage polarization with a concomitant improvement of motor function in models of spinal cord injury induced in mice (Sun et al, 2018) and in rats (Romanelli et al, 2019), respectively.
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