Egorov E E, Moldaver M V, Vishniakova Kh S, Terekhov S M, Dashinimaev E B, Cheglakov I B, Toropygin I Iu, Iarygin K N, Chumakov P M, Korochkin L I, Antonova G A, Rybalkina E Iu, Saburina I N, Burnaevskiĭ N S, Zelenin A V
Ontogenez. 2007 Mar-Apr;38(2):105-19.
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 auto-transplantation to senior people, when the cell proliferative potential is markedly reduced and accessibility of stem cells is significantly restricted.
此前已获得成人皮肤端粒化成纤维细胞的克隆。结果表明，尽管这些细胞在大规模培养中生长迅速，但形成集落的能力较差。条件培养基、抗氧化剂和降低的局部氧分压可增强其集落形成能力，但未达到初始细胞的特征水平。端粒化细胞的条件培养基比初始细胞的条件培养基在更大程度上增强了集落形成。对端粒化成纤维细胞蛋白质组的研究揭示了数十个基因活性的变化。总体趋势是细胞骨架的弱化和不稳定性增加以及控制蛋白质降解机制的激活。然而，这些变化并不十分明显。在永生化端粒化细胞形成过程中会发生选择，这似乎决定了一些基因表达的变化。有人提出，端粒化细胞集落形成能力的下降是由于这些细胞对细胞间接触的需求增加。只有在最大的集落中，细胞生长速率才达到大规模培养的特征速率。在这方面，端粒化成纤维细胞类似于干细胞：它们能够自我维持，但在缺乏由其他成纤维细胞代表的相应微环境（生态位）时“转向”分化。在集落形成试验中不分裂的细胞应被视为分化细胞，因为它们没有降解特征，保持活力，能活跃移动、生长、吞噬碎片等。研究还表明，端粒化并不妨碍成肌细胞和人类神经干细胞的分化。因此，所获得的结果表明端粒化细胞中存在正常的增殖调控机制，这为其在细胞治疗中的应用开辟了可能性，特别是在自体移植给老年人的情况下，此时细胞增殖潜能明显降低且干细胞的可及性显著受限。
