Key findings
- Successful reprogramming of PBMCs using synthetic RNA
We have successfully established induced pluripotent stem (iPS) cells from peripheral blood mononuclear cells (PBMCs) using synthetic RNA, which has been a technical challenge until now.
- Dramatic improvement in reprogramming efficiency by inhibiting the p53 pathway
Introducing MDM4, a negative regulator of p53, significantly enhanced the reprogramming efficiency of PBMCs using RNA.
- The S367A mutant of MDM4 is the most effective
Among various MDM4 mutants tested, the S367A variant, which is resistant to ubiquitin-mediated degradation, exhibited the highest effectiveness.
- Established PBMC-derived iPS cells can differentiate into corneal cells
The generated iPS cells demonstrated the ability to differentiate into all three germ layers, including successful induction into corneal epithelial-like cells, confirming their pluripotency.
- Protocol publication
The somatic cell (HDF and PBMC) reprogramming protocols, using synthetic RNA, have been published on the CiRA website in both Japanese and English.
A research group led by Dr. Masato Nakagawa (Specially Appointed Associate Professor (Full Time), WPI-PRIMe, and Junior Associate Professor at the Center for iPS Cell Research and Application (CiRA), Kyoto University), has established a highly efficient method for generating induced pluripotent stem (iPS) cells from human peripheral blood mononuclear cells (PBMCs) using synthetic RNA. This study offers an effective solution to the longstanding challenge of non-viral iPS cell generation from human blood cells, potentially contributing to future applications in regenerative and personalized medicine. The findings have been published in the open-access journal Scientific Reports.
| Title | MDM4 enables efficient human iPS cell generation from PBMCs using synthetic RNAs |
| Authors | Masato Nakagawa1,2,6*, Mizuho Nogi1,6, Hatsuki Doi1, Ryuhei Hayashi3,4, Tomohiko Katayama2,3, Hirohisa Ohno1, Megumi Mochizuki1, Karin Hayashi1, Hirohide Saito1,5 (*Corresponding Author) |
| DOI | 10.1038/s41598-025-16446-y |
| Journal | Scientific Reports |
| Published date | September 8, 2025 |