한빛사 논문
Abstract
Hyun-Jai Cho1, Choon-Soo Lee1, Yoo-Wook Kwon2, Jae Seung Paek1, Sun-Hee Lee1, Jin Hur1, Eun Ju Lee1, Tae-Young Roh3, In-Sun Chu4, Sun-Hee Leem5, Youngsoo Kim6, Hyun-Jae Kang7, Young-Bae Park1 and Hyo-Soo Kim8,*
1 National Research Laboratory for Cardiovascular Stem Cell, Seoul National University Hospital, Seoul, Korea, Republic of; 2 Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea, Republic of; 3 Division of Integrative Biosciences and Biotechnology, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea, Republic of; 4 Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea, Republic of; 5 Department of Biological Science, Dong-A University, Busan, Korea, Republic of; 6 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, Republic of; 7 Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of; 8 Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea, Republic of
* Corresponding author
Abstract
The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application. We report that that a single transfer of ESC (embryonic stem cell)-derived proteins into primarily cultured adult mouse fibroblasts, rather than repeated transfer or prolonged exposure to materials, can achieve full reprogramming up to the pluripotent state without the forced expression of ectopic transgenes. During the process, gene expression and epigenetic status were converted from somatic to ES-equivalent status. We verified that protein-based reprogramming was neither by the contamination of protein donor ESC nor by DNAs/RNAs from donor ESC. Protein-iPS cells were biologically and functionally very similar to ES cells and differentiated into 3-germ layers in vitro. Furthermore, Protein-iPS cells possessed in vivo differentiation (well-differentiated teratoma formation) and development (chimeric mice generation and a tetraploid blastocyst complementation) potentials. Our results provide an alternative and safe strategy for the reprogramming of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy.
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