Isolation of Mesenchymal Stem Cells (MSCs) from Wharton’s Jelly (WJ) Tissue of Human Umbilical Cord (hUC); a Protocol

Mesenchymal stem cells (MSCs) with their spindle like shapes are a lineage of stem cells with the capacity to self-renew and differentiate into osteoblasts, adipocytes, and chondrocytes and with CD105, CD73, and CD90 expression and the lack of CD34, CD14, CD45, and HLA - DR expression. The immunomodulatory, angiogenic, antiapoptotic, antimicrobial, and antioxidative characteristics of these cells made them more attractive in the field of cell - therapy for several autoimmune and inflammatory diseases, including diabetes, neurological disorders, sepsis, cardiac ischemia, and GvHD. For this reason, various protocols have been proposed to isolate mesenchymal stem cells from different tissue sources, such as adipose tissue (AT), umbilical cord (UC), Wharton’s jelly (WJ), bone marrow (BM), dental pulp, and even menstrual fluid. Considering the ease of access to the umbilical cord tissue and the fact that this tissue is rich in MSCs with embryonic origin and higher proliferation rate and lower senescence of the cells, the umbilical cord became a suitable source for explant MSC culture. In this study, we decided to introduce an explant culture protocol of MSCs that is less expensive and cost - effective achieving a high yield of MSCs

Cancer-associated mesenchymal stem/stromal cells: role in progression and potential targets for therapeutic approaches

Malignancies contain a relatively small number of Mesenchymal stem/stromal cells (MSCs), constituting a crucial tumor microenvironment (TME) component. These cells comprise approximately 0.01–5% of the total TME cell population. MSC differentiation potential and their interaction with the tumor environment enable these cells to affect tumor cells’ growth, immune evasion, metastasis, drug resistance, and angiogenesis. This type of MSC, known as cancer-associated mesenchymal stem/stromal cells (CA-MSCs (interacts with tumor/non-tumor cells in the TME and affects their function by producing cytokines, chemokines, and various growth factors to facilitate tumor cell migration, survival, proliferation, and tumor progression. Considering that the effect of different cells on each other in the TME is a multi-faceted relationship, it is essential to discover the role of these relationships for targeting in tumor therapy. Due to the immunomodulatory role and the tissue repair characteristic of MSCs, these cells can help tumor growth from different aspects. CA-MSCs indirectly suppress antitumor immune response through several mechanisms, including decreasing dendritic cells (DCs) antigen presentation potential, disrupting natural killer (NK) cell differentiation, inducing immunoinhibitory subsets like tumor-associated macrophages (TAMs) and Treg cells, and immune checkpoint expression to reduce effector T cell antitumor responses. Therefore, if these cells can be targeted for treatment so that their population decreases, we can hope for the treatment and improvement of the tumor conditions. Also, various studies show that CA-MSCs in the TME can affect other vital aspects of a tumor, including cell proliferation, drug resistance, angiogenesis, and tumor cell invasion and metastasis. In this review article, we will discuss in detail some of the mechanisms by which CA-MSCs suppress the innate and adaptive immune systems and other mechanisms related to tumor progression

Oleuropein reduces LPS-induced inflammation via stimulating M2 macrophage polarization

Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-β). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis