Human Wharton’s Jelly-Derived Mesenchymal Stromal Cells Primed by Tumor Necrosis Factor-α and Interferon-γ Modulate the Innate and Adaptive Immune Cells of Type 1 Diabetic Patients

Abstract

The unique immunomodulation and immunosuppressive potential of Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) make them a promising therapeutic approach for autoimmune diseases including type 1 diabetes (T1D). The immunomodulatory effect of MSCs is exerted either by cell-cell contact or by secretome secretion. Cell-cell contact is a critical mechanism by which MSCs regulate immune-responses and generate immune regulatory cells such as tolerogenic dendritic cells (tolDCs) and regulatory T cell (Tregs). In this study, we primed WJ-MSCs with TNF-α and IFN-γ and investigated the immunomodulatory properties of primed WJ-MSCs on mature dendritic cells (mDCs) and activated T cells differentiated from mononuclear cells (MNCs) of T1D patient’s. Our findings revealed that primed WJ-MSCs impaired the antigen-mediated immunity, upregulated immune-tolerance genes and downregulated immune-response genes. We also found an increase in the production of anti-inflammatory cytokines and suppression of the production of pro-inflammatory cytokines. Significant upregulation of FOXP3, IL10 and TGFB1 augmented an immunosuppressive effect on adaptive T cell immunity which represented a strong evidence in support of the formation of Tregs. Furthermore, upregulation of many critical genes involved in the immune-tolerance mechanism (IDO1 and PTGES2/PTGS) was detected. Interestingly, upregulation of ENTPD1/NT5E genes express a strong evidence to switch immunostimulatory response toward immunoregulatory response. We conclude that WJ-MSCs primed by TNF-α and IFN-γ may represent a promising tool to treat the autoimmune disorders and can provide a new evidence to consider MSCs- based therapeutic approach for the treatment of TID.

Mesenchymal stromal cells from human Wharton’s jelly modulate the intraocular immune response in a glucocorticoid hypertension model: an exploratory analysis

“…Contrary to what was observed by Mrahleh et al [59] in an in vitro study of hWJ-MSCs, no increase in IL-10 concentration was observed in the cell therapy groups. However, this cytokine increased slightly in the OH group than in the untreated eyes.…”

“…This increase can be observed in stressful situations such as immune reactions, inflammation, ischemia, hypoxia, and oxidative stress [64]. In contrast, the OH group that received hWJ-MSCs showed a decrease in the level of this cytokine, which is consistent with other reports [59]. These findings demonstrated the potential immunomodulatory effects of these cells.…”

“…The hWJ-MSC group without OH was the only group with TCD4 + -cell infiltration in the GCL. This may be due to the immunomodulatory effect of MSCs through the activation of immunoregulatory cells such as tolerogenic dendritic cells and regulatory T cells, which are capable of inhibiting antigen-specific T-cell responses [59].…”

Recommendation: Treatment of clinical long COVID encephalopathies with nasal administered mesenchymal stromal cell extracellular vesicles

“…In fact, our quantitative study showed that multiple IV injections of the sEVs over days can be needed to reach quantitative maximum healing that is produced by single MSC injections (Nakazaki et al, 2021). More clinical studies of similar benefits of MSC and MSC-EVs in patients have been published (Weiss et al, 2013;Nassar et al, 2016;Stolk et al, 2016;Mrahleh et al, 2021) Currently, there are 199 listed NIH clinical trials involving MSC, 52 trials on sEVs, some with MSC-secreted EVs, that are now just beginning to come to favorable published conclusion.…”

Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies

“…Mesenchymal stem cells (MSCs) play important roles in regenerative medicine due to their potential for self-renewal and multi-directional differentiation [ 1 ]. MSCs were also found to have strong immunoregulation capabilities caused by the secretion of various signal factors or cell to cell contact [ 2 ].…”