Induction of Expandable Adipose-Derived Mesenchymal Stem Cells from Aged Mesenchymal Stem Cells by a Synthetic Self-Replicating RNA.
Chika Miyagi-ShiohiraYoshiki NakashimaNaoya KobayashiShinji KitamuraIssei SaitohMasami WatanabeHirofumi NoguchiPublished in: International journal of molecular sciences (2018)
Adipose-derived mesenchymal stem cells (ADSCs) have attracted attention due to their potential for use in the treatment of various diseases. However, the self-renewal capacity of ADSCs is restricted and their function diminishes during passage. We previously generated induced tissue-specific stem cells from mouse pancreatic cells using a single synthetic self-replicating Venezuelan Equine Encephalitis (VEE)-reprogramming factor (RF) RNA replicon (SR-RNA) expressing the reprogramming factors POU class 5 homeobox 1 (OCT4), Krueppel-like factor 4 (KLF4), Sex determining region Y-box 2 (SOX2), and Glis Family Zinc Finger 1 (GLIS1). This vector was used to generate induced pluripotent stem (iPS) cells. Here, we applied this SR-RNA vector to generate human iTS cells from aged mesenchymal stem cells (hiTS-M cells) deficient in self-renewal that were derived from adipose tissue. These hiTS-M cells transfected with the SR-RNA vector survived for 15 passages. The hiTS-M cells expressed cell surface markers similar to those of human adipose-derived mesenchymal stem cells (hADSCs) and differentiated into fat cells and osteoblasts. Global gene expression profiling showed that hiTS-M cells were transcriptionally similar to hADSCs. These data suggest that the generation of iTS cells has important implications for the clinical application of autologous stem cell transplantation.
Keyphrases
- induced apoptosis
- cell cycle arrest
- mesenchymal stem cells
- adipose tissue
- stem cell transplantation
- bone marrow
- endothelial cells
- oxidative stress
- endoplasmic reticulum stress
- machine learning
- cell death
- risk assessment
- insulin resistance
- signaling pathway
- genome wide
- cell therapy
- skeletal muscle
- artificial intelligence
- big data
- binding protein
- replacement therapy
- nucleic acid
- pluripotent stem cells
- genome wide identification