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Mitochondrial Genome Mutations in Mesenchymal Stem Cells derived from Human Dental Induced Pluripotent Stem Cells
Jumi Park1,2,#, Yeonmi Lee1,#, Joosung Shin1, Hyeon-Jeong Lee2, Young-Bum Son2, Bong-Wook Park3, Deokhoon Kim4, Gyu-Jin Rho2, Eunju Kang1,*
1Department of Convergence Medicine & Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine,
2Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University,
3Department of Dentistry, Gyeongsang National University School of Medicine, Institute of Health Science,
4Department of Pathology, Asan Institute for life sciences, Asan Medical Center, University of Ulsan College of Medicine
Abstract
Ethical and safety issues have rendered mesenchymal stem cells (MSCs) popular candidates in regenerative medicine, but their therapeutic capacity is lower than that of induced pluripotent stem cells (iPSCs). This study compared original, dental tissue-derived MSCs with re-differentiated MSCs from iPSCs (iPS-MSCs). CD marker expression in iPS-MSCs was similar to original MSCs. iPS-MSCs expressed higher in pluripotent genes, but lower levels in mesodermal genes than MSCs. In addition, iPS-MSCs did not form teratomas. All iPSCs carried mtDNA mutations; some shared with original MSCs and others not previously detected therein. Shared mutations were synonymous, while novel mutations were non-synonymous or located on RNA-encoding genes. iPS-MSCs also harbored mtDNA mutations transmitted from iPSCs. Selected iPS-MSCs displayed lower mitochondrial respiration than original MSCs. In conclusion, screening for mtDNA mutations in iPSC lines for iPS-MSCs can identify mutation-free cell lines for therapeutic applications.
Abstract, Accepted Manuscript(in press) [Submitted on February 13, 2019, Accepted on June 12, 2019]
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