Biochemical and molecular inducers and modulators of M2 macrophage polarization in clinical perspective

•M2 macrophages are a potential therapeutic agent for inflammatory diseases.•Creation of a therapeutic cell products requires precise control of the macrophage polarization process.•Mitochondrial biogenic polyamines, miRNAs, cell surface receptors, efferocytosis regulators control macrophage plasticity.•Stable polarization should be achieved to unlock the therapeutic potential of M2 macrophages.•Genetic modifications inducing M2 polarization may solve this problem of the modern regenerative medicine. Macrophages as innate immune cells with great plasticity are of great interest for cell therapy. There are two main macrophage populations – pro- and anti-inflammatory cells also known as M1 and M2. High potential in cancer research contributed to the in-depth study of the molecular processes leading to the polarization of macrophages into the M1 phenotype, and much less attention has been paid to anti-inflammatory M2 macrophages, which can be successfully used in cell therapy of inflammatory diseases. This review describes ontogenesis of macrophages, main functions of pro- and and-inflammatory cells and four M2 subpopulations characterized by different functionalities. Data on agents (cytokines, microRNAs, drugs, plant extracts) that may induce M2 polarization through the changes in microenvironment, metabolism, and efferocytosis are summarized. Finally, recent attempts at stable macrophage polarization using genetic modifications are described. This review may be helpful for researchers concerned with the problem of M2 macrophage polarization and potential use of these anti-inflammatory cells for the purposes of regenerative medicine.