Cocktail of Chemical Compounds and Recombinant Proteins Robustly Promote the Stemness of Adipose-Derived Stem Cells

Abstract Induced pluripotent stem cells (iPSCs) from somatic cells can be reprogrammed to provide an unlimited cell resource showing great potential in disease modeling and regenerative medicine. However, the traditional method for reprogramming cells into iPSCs using genome-integrating retro- or lenti-viruses remain an obstacle for its application in clinical settings. We tried the possibility to generate pre-iPSCs from human adipose-derived stem cells (ADSCs) by nongenetic reprogramming using recombinant cell-penetrating proteins OCT4/KLF4/SOX2 (PTD-OKS) and the cocktail of small molecules (VCFZ). Our experimental results demonstrated that PTD-OKS in combination with VCFZ (VCFZ+OKS) could significantly enhance the stemness of ADSCs and easily get pre-iPSCs after 25 days treatments. The pre-iPSCs showed similar morphology to iPSCs, which were positive for alkaline phosphatase staining. Furthermore, RT-polymerase chain reaction analysis showed that VCFZ+OKS could significantly upregulate the expression of...