KMID : 0624620230560080463
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BMB Reports 2023 Volume.56 No. 8 p.463 ~ p.468
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Selection of iPSCs without mtDNA deletion for autologous cell therapy in a patient with Pearson syndrome
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Lee Yeon-Mi
Han Jong-Suk Hwang Sae-Byeok Kang Soon-Suk Son Hyeoung-Bin Jin Chae-Yeon Kim Jae-Eun Lee Beom-Hee Kang Eun-Ju
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Abstract
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Screening for genetic defects in the cells should be examined for clinical application. The Pearson syndrome (PS) patient harbored nuclear mutations in the POLG and SSBP1 genes, which could induce systemic large-scale mitochondrial genome (mtDNA) deletion. We investigated iPSCs with mtDNA deletions in PS patient and whether deletion levels could be maintained during differentiation. The iPSC clones derived from skin fibroblasts (9% deletion) and blood mononuclear cells (24% deletion) were measured for mtDNA deletion levels. Of the 13 skin-derived iPSC clones, only 3 were found to be free of mtDNA deletions, whereas all blood-derived iPSC clones were found to be free of deletions. The iPSC clones with (27%) and without mtDNA deletion (0%) were selected and performed in vitro and in vivo differentiation, such as embryonic body (EB) and teratoma formation. After differentiation, the level of deletion was retained or increased in EBs (24%) or teratoma (45%) from deletion iPSC clone, while, the absence of deletions showed in all EBs and teratomas from deletion-free iPSC clones. These results demonstrated that non-deletion in iPSCs was maintained during in vitro and in vivo differentiation, even in the presence of nuclear mutations, suggesting that deletion-free iPSC clones could be candidates for autologous cell therapy in patients.
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KEYWORD
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EB formation, iPSCs, mtDNA deletion, PS patient, Teratoma formation
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