Adult Stem Cells in Hibernation: Future Perspectives of Space Travel.

Space traveling is imperative for mankind in the future. Expectedly, hibernation will become an option for space traveler to overcome the endless voyage. With regard to some of the studies pointed out that during hibernation, muscle will undergo atrophy and meantime neurogenesis will reduce, these obstacles were frequently related with stem cell regeneration. Thus, investigation on whether hibernation will lead to dysfunction of stem cell becomes an important issue. By going through four main systems in this article, such as, hematopoietic system, skeletal muscle system, central nervous system and orthopedic system, we are expecting that stem cells regeneration capacity will be affected by hibernation. To date, these researches are majorly the read-out from short term or seasonal hibernating mammals. Proposing and creating a simulated long-term hibernation animal model is turning essential for the further investigation on the effect of longer period of hibernation to human stem cells.

Autocrine VEGF signalling on M2 macrophages regulates PD-L1 expression for immunomodulation of T cells.

M2-polarized macrophages, on one hand, can promote tumour vascularization by producing proangiogenic factors, such as vascular endothelial growth factor (VEGF). On the other hand, the expression of VEGF receptors (VEGFR) in this cell lineage was also reported. Although the function of VEGF/VEGFR axis plays a pivotal role in macrophages infiltration and angiogenesis, however, there is still lack of the direct evidence to show the role of VEGF as an autocrine operating in M2 macrophages, particularly for immunomodulation. In our study, we surprisingly discovered that M2 macrophages polarized by baicalin can simultaneously express VEGF and its receptors. Taking advantage of this unique culture system, we were able to investigate the biological activity of M2 macrophages in response to the autocrine VEGF milieu. Our results showed that the expression of programmed death-ligand 1 (PD-L1) on M2 macrophages was significantly up-regulated in autocrine VEGF milieu. Through the blockade of autocrine VEGF signalling, PD-L1 expression on M2 macrophages was dramatically down-regulated. Furthermore, transplantation of PD-L1+ M2 macrophage stimulated by autocrine VEGF into allogeneic mice significantly suppressed host CD4+ /CD8+ T cells in the peripheral blood and increased CD4+ CD25+ regulatory T cells in the bone marrow. In conclusion, our findings provide a novel biological basis to support the current successful strategy using combined VEGF/PD-1 signalling blockade in cancer therapy.

M2C Polarization by Baicalin Enhances Efferocytosis via Upregulation of MERTK Receptor.

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2C phenotype by baicalin. The signatures of M2C macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF- α ), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2A rather than M2C subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2C macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2C macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.