Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MPhis). Therefore this study has been committed to explore how MSCs may modify the effect of MPhi polarization upon an inductive environment using mouse bone marrow (BM)-derived "naive", unpolarized MPhis. Phagocytosis of various MPhi subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFalpha production of MPhi subtypes since M1 and M2b MPhis produced less and M2a produced higher amount of TNFalpha while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFalpha dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFalpha and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naive BM-MPhis. Similarly, polarization of M1 to M2b MPhis was successful showing increase in IL-10 and reduction in TNFalpha levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MPhis and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MPhis

Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues

Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus

Participation of mesenchymal stem cells in the regulation of immune response and cancer development

The relevance of the microenvironment in the initiation, promotion, and progression of cancer has been postulated. Mesenchymal stem cells (MSCs) have been identified as important components of the tumor stroma, which are capable of affecting the development of cancer through various mechanisms. In particular, MSCs immunosuppressive properties play an important role. It has been shown that bone marrow-derived and other healthy tissues-derived MSCs are capable of regulating the immune response by affecting the activation, maturation, proliferation, differentiation, and effector function of cells of the immune system, such as neutrophils, macrophages, dendritic cells, natural killer cells (NK) and T-lymphocytes. Similar mechanisms have been identified in MSCs associated with different types of tumors, where they generate an immunosuppressive microenvironment by decreasing the cytotoxic activity of T-lymphocytes and NK cells, skew macrophage differentiation towards an M2 phenotype, and decrease the secretion of Th1-type cytokines. Also, the cytokines, chemokines, and factors secreted by the transformed cells or other cells from the tumor stroma are capable of modulating the functions of MSCs

Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential

Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied

Human Bone Marrow Mesenchymal Stem/Stromal Cells Exposed to an Inflammatory Environment Increase the Expression of ICAM-1 and Release Microvesicles Enriched in This Adhesive Molecule: Analysis of the Participation of TNF-α and IFN-γ

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory capacity; therefore, they have been used in different clinical protocols in which it is necessary to decrease the immune response. This capacity is mainly regulated by TNF-α and IFN-γ, and it has been observed that cell-cell contact, mainly mediated by ICAM-1, is important for MSCs to carry out efficient immunoregulation. Therefore, in the present work, we analyzed the effect of TNF-α alone or in combination with IFN-γ on the expression of ICAM-1. Besides, given the importance of cell contact in the immunoregulatory function of MSCs, we analyzed whether these cells release ICAM-1+ microvesicles (MVs). Our results show for the first time that TNF-α is capable of increasing the early expression of ICAM-1 in human BM-MSCs. Also, we observed that TNF-α and IFN-γ have a synergistic effect on the increase in the expression of ICAM-1. Furthermore, we found that BM-MSCs exposed to an inflammatory environment release MVs enriched in ICAM-1 (MVs-ICAM-1high). The knowledge generated in this study will contribute to the improvement of in vitro conditioning protocols that favor the therapeutic effect of these cells or their products