Clones of telomerized fibroblasts of adult human skin have earlier been obtained. It was shown that despite their fast growth in mass cultures, these cells poorly form colonies. Conditioned medium, antioxidants, and reduced partial oxygen pressure enhanced their colony formation, but not to the level characteristic of the initial cells. The conditioned medium of telomerized cells enhanced colony formation to a much greater extent than that of the initial cells. A study of proteome of the telomerized fibroblasts has revealed changes in the activities of tens of genes. A general trend consists in weakening and increased lability of the cytoskeleton and in activation of the mechanisms controlling protein degradation. However, these changes are not very pronounced. During the formation of immortal telomerized cells, selection takes place, which appears to determine changes in the expression of some genes. It was proposed that a decrease in the capacity of telomerized cells for colony formation is due to increased requirements of these cells to cell-cell contacts. The rate of cell growth reached that characteristic of mass cultures only in the largest colonies. In this respect, the telomerized fibroblasts resembled stem cells: they are capable of self-maintenance, but “escape” to differentiation in the absence of the corresponding microenvironment (niche), which is represented by other fibroblasts. Nondividing cells in the test of colony formation should be regarded as differentiated cells, since they have no features of degradation, preserve their viability, actively move, grow, phagocytize debris, etc. It was also shown that telomerization did not prevent differentiation of myoblasts and human neural stem cells. Thus, the results obtained suggest the existence of normal mechanisms underlying the regulation of proliferation in the telomerized cells, which opens possibilities of their use in cell therapy, especially in the case of autotransplantation to senior people, when the cell proliferative potential is markedly reduced and accessibility of stem cells is significantly restricted.
1 March 2009 in Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology
Hair growth is a highly complex process regulated at multiple levels, including molecular pathways, stem cell behavior, metabolic processes, and immune responses. The hair follicle exhibits metabolic compartmentalization, with some cells relying on glycolysis and others on oxidative phosphorylation. Interestingly, in mice, the onset of the anagen phase can be stimulated by locally suppressing oxidative phosphorylation in the skin. This study showed that topical application of palmitate or oleate accelerated the onset of anagen in mice, while lactate, the end product of glycolysis, delayed it. We also investigated the effects of fatty acids on cytokine production in various human cell cultures. Fatty acids did not induce a cytokine response in fibroblasts or keratinocytes but significantly affected monocytes. Specifically, palmitic acid induced the production of TNF-α, IL-8, and CCL2. Oleic acid, however, elicited almost no response. By comparing the “metabolic” and “inflammatory” hypotheses of anagen stimulation, the results of our study suggest that metabolic regulation holds significant promise for influencing hair growth.