Abstract
Mesenchymal stem cells (MSCs) and their secreted molecules have shown great potential for tissue regeneration and the treatment of inflammation and autoimmune diseases. However, they can also be associated with therapeutic failure or even side effects. Possible causes for this could include the state of the stem cells themselves and the influence of the local microenvironment, wherein macrophages play important roles. As such, we utilized conditioned medium from bone marrow-derived MSCs (MSC-CM) and studied its effect on different macrophage subsets. Effects on macrophage proliferation, apoptosis, polarization, and phagocytosis were determined, and it was discovered that MSC-CM had no significant effect on macrophage proliferation but inhibited M0 macrophage apoptosis and marginally induced M1 macrophage apoptosis. MSC-CM was shown to reduce CD80 expression on the surface of M1 macrophages. Moreover, it promoted and inhibited CD163 expression on the surface of M0 and M1 macrophages, respectively. However, MSC-CM tended to initially promote CD163 expression on M2 macrophages but inhibited expression of this marker after additional incubation time. Unlike MSCs, MSC-CM had no significant effect on the expression of TNF-α and IL-10 in macrophages. Thus, the effect of MSC-CM on different types of macrophages is different, and after stem cells are implanted, their effects on the local immune microenvironment are closely related to the original immune status of the implantation site. Therefore, we suggest that when utilizing stem cells for therapeutics, the immune status of the treatment site should be fully elucidated.
Highlights
In recent years, mesenchymal stem cells (MSCs) have received remarkable attention for tissue regeneration and the treatment of inflammation and autoimmune diseases; they have shown good potential for application, but failure and even side effects have been reported in some clinical trials [1,2,3]
Microscopic observation revealed that bone marrow-derived cell populations began to gradually adhere on the second day; on the fourth day, cell morphology was relatively stable and was a characteristic of that of macrophages
Unstimulated macrophages showed no expression of surface CD80, whereas those treated with LPS and IFN-γ exhibited increased expression of CD80 (Figure 1(b)) and inducible nitric oxide synthase (iNOS) (Figure 1(c)), which was consistent with the characteristics of M1 macrophages
Summary
Mesenchymal stem cells (MSCs) have received remarkable attention for tissue regeneration and the treatment of inflammation and autoimmune diseases; they have shown good potential for application, but failure and even side effects have been reported in some clinical trials [1,2,3]. Given the complexity of the immune system and the important role of macrophages in inflammation and regeneration [6, 8,9,10], we selected macrophages, the participants and regulators of immune system, as the basis of our research. Because of their functional diversity, macrophages play critical roles in immune regulation, development, and tissue remodeling [11]. Macrophages are the most plastic cells and are usually divided into two phenotypes including classical activated M1 macrophages and alternatively activated M2 macrophages [12]
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