간 유래 중간엽 줄기세포에서 p21을 통한 miR-34a의 노화 조절 연구

Abstract

Mesenchymal stem cells (MSCs) are ideal for cell therapy since they possess the characteristics of stem cells and immunomodulatory properties. However, there is a disadvantage in that it is difficult to maintain function for a long time compared to its potential, so many researchers are continuing their efforts to understand the aging of MSCs. In this study, we investigated microRNAs (miRNAs) that may play significant roles in the aging process by monitoring cell senescence in liver-derived MSCs (LD-MSCs). To identify the characteristics of senescent cells, this study examined mRNA expression of senescence-associated factors and their related miRNA expression level using qRT-PCR in early and late passage LD-MSCs. A morphological difference in early and late passage cells was observed through optical diffraction tomography (ODT). As a result, differences between early passage and late passage cells were observed. In comparing the morphology of early and late passaged cells, alterations in the structure of the cells were observed. To analyze the internal structure of cells using ODT, an increase in cell size, multinucleation, and vacuoles were observed. In addition, lipid droplets known to regulate cell metabolism were found to be reduced in late passage cells. P21 is known to be a senescence-related factor that induces cell cycle arrest. Late passage LD-MSCs expressed higher levels of p21, and differences in the expression of several miRNAs were identified to select miRNAs capable of regulating p21. MiR-106b, a representative p21 suppressor, observed no significant differences over time. While miR-34a, known to induce p21, is more abundant in late passage LD-MSCs. The miR-34a has the potential to regulate senescence of LD-MSCs. Taken together, LD-MSCs in late passage showed a distinct morphological difference, and p21 regulates cellular senescence by arresting the cell cycle. Through the induction of the expression of p21, miR-34a has the potential to promote cellular senescence. This suggests that miR-34a can be a potential regulator of cellular senescence via p21 expression induction.