한빛사 논문
Abstract
Yong-Hee Rhee1,2,3, Ji-Yun Ko1,2, Mi-Yoon Chang4, Sang-Hoon Yi1,2, Dohoon Kim4, Chun-Hyung Kim4, Jae-Won Shim1, A-Young Jo1, Byung-Woo Kim1,2, Hyunsu Lee5, Suk-Ho Lee5, Wonhee Suh6, Chang-Hwan Park2,3, Hyun-Chul Koh2,7, Yong-Sung Lee1,2,3, Robert Lanza8, Kwang-Soo Kim4,6 and Sang-Hun Lee1,2
1Department of Biochemistry and Molecular Biology, College of Medicine,
2Hanyang Biomedical Research Institute, and
3Graduate School of Biomedical and Engineering, Hanyang University, Seoul, Republic of Korea.
4Molecular Neurobiology Laboratory, Department of Psychiatry and Harvard Stem Cell Institute, McLean Hospital/Harvard Medical School, Belmont, Massachusetts, USA.
5Cell Physiology Laboratory, Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
6CHA Stem Cell Institute, CHA University, Seoul, Republic of Korea.
7Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
8Stem Cell and Regenerative Medicine International, Marlborough, Massachusetts, USA.
Address correspondence to: Sang-Hun Lee, Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea. Phone: 82.2.2220.0625; Fax: 82.2.2294.6270. Or to: Kwang-Soo Kim, Molecular Neurobiology Laboratory, McLean Hospital, 115 Mill St., Belmont, Massachusetts 02478, USA.
Authorship note: Yong-Hee Rhee, Ji-Yun Ko, and Mi-Yoon Chang contributed equally to this work.
Published May 16, 2011
Received for publication November 15, 2010, and accepted in revised form April 6, 2011.
Parkinson disease (PD) involves the selective loss of midbrain dopamine (mDA) neurons and is a possible target disease for stem cell?based therapy. Human induced pluripotent stem cells (hiPSCs) are a potentially unlimited source of patient-specific cells for transplantation. However, it is critical to evaluate the safety of hiPSCs generated by different reprogramming methods. Here, we compared multiple hiPSC lines derived by virus- and protein-based reprogramming to human ES cells (hESCs). Neuronal precursor cells (NPCs) and dopamine (DA) neurons delivered from lentivirus-based hiPSCs exhibited residual expression of exogenous reprogramming genes, but those cells derived from retrovirus- and protein-based hiPSCs did not. Furthermore, NPCs derived from virus-based hiPSCs exhibited early senescence and apoptotic cell death during passaging, which was preceded by abrupt induction of p53. In contrast, NPCs derived from hESCs and protein-based hiPSCs were highly expandable without senescence. DA neurons derived from protein-based hiPSCs exhibited gene expression, physiological, and electrophysiological properties similar to those of mDA neurons. Transplantation of these cells into rats with striatal lesions, a model of PD, significantly rescued motor deficits. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of PD.
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