Abstract
Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton’s jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis.
Highlights
Previous reports demonstrated promising therapeutic effects of mesenchymal stem cells through immunosuppressive, angiomodulatory, and paracrine factor activities [1,2,3].MSC paracrine secretome plays important immunomodulation in both the innate and the adaptive immune system by suppression of CD4 and CD8 T cells activation/proliferation and pro-inflammatory type 1 helper T cells (Th1) [4]
We found that TSG treatment significantly increased total protein concentration of extracellular vesicles (EVs) secreted by Wharton’s jelly-derived MSCs (WJ-MSCs), with 1 μM TSG showing the greatest effect on EV production
The potential of MSCs as a powerful resource for target diseases is under active exploration in numerous clinical trials, use of MSCs comes with several affiliated concerns, such as difficulty providing a consistent supply with phenotypic/functional stability as well as the high cost of isolation and handling
Summary
Previous reports demonstrated promising therapeutic effects of mesenchymal stem cells MSCs) through immunosuppressive, angiomodulatory, and paracrine factor activities [1,2,3]. MSC paracrine secretome plays important immunomodulation in both the innate and the adaptive immune system by suppression of CD4 and CD8 T cells activation/proliferation and pro-inflammatory type 1 helper T cells (Th1) [4]. Among the MSC secretome, MSC-derived extracellular vesicles (EVs) have recently attracted attention. EVs are lipid bilayer vesicles secreted by cells into the extracellular matrix and play an important role in cell-to-cell communication. MSC EVs promote activation of immune regulatory pathways by transferring proteins, mRNAs, microRNAs (miRNAs), and other components to target cells [11]. The function and cargo of EVs differ according to cell type, and cell stress can affect the cargo of EVs [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
