The generation and properties of human M2-like macrophages: potential candidates for CNS repair?

Regulation of the immune response seems to be a promising strategy for a successful central nervous system (CNS) repair, and macrophages are considered to be prospective candidates for cell therapy. Using low serum conditions we generated human anti-inflammatory M2-like macrophages from peripheral blood monocytes and compared these cells (termed Mφ3) with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2, generated in the presence of GM-CSF and M-CSF. We focused primarily on the differences in T-cell stimulatory activity and production of various cytokines, chemokines, and growth factors. Low serum conditions had no negative impact on macrophage yield, the largest of which was for Mφ3. We showed that Mφ3 more closely resembled Mφ2 than Mφ1. Mφ2 and particularly Mφ3, but not Mφ1 expressed relatively low levels of CD86 and failed to stimulate T-cell proliferation. In contrast to pro-inflammatory Mφ1, unstimulated Mφ3 produced significantly lower levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-12) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4) coupled with a higher IL-10 level. Moreover, concentrations of IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in Mφ-3 supernatants were lower not only when compared to Mφ1, but also to Mφ2 cultures. Like Mφ1 and Mφ2, Mφ3 was capable of producing neurotrophic- (BDNF, IGF-1), angiogenic- (VEGF), and other growth factors (EPO, G-CSF, FGF-basic, EGF) with neuroprotective and regenerative activity. In fact, IGF-1 production by Mφ-3 exceeds secretion of this factor by Mφ-1 and Mφ-2 by more than 25 fold. Thus, generated Mφ-3 represented M2-like macrophages with high regenerative potential.