Spinal muscular atrophy (SMA) is primarily a neurodegenerative disease caused by the homozygous deletion of the survival motor neuron 1 (SMN1) gene, thereby reducing SMN protein expression. Mesenchymal stem cells (MSCs) have been implicated in the treatment of SMA. In the present study, we overexpressed exogenous SMN1 at the ribosomal DNA (rDNA) locus of induced pluripotent stem cells (iPSCs) generated from a SMA patient using an rDNA-targeting vector. The gene-targeted patient iPSCs differentiated into MSCs (SMN1-MSCs). A 2.1-fold higher expression level of SMN protein was detected in SMN1-MSCs than that detected in MSCs derived from patient iPSCs, and the results of the immunofluorescence analysis showed no difference in the quantity of SMN nuclear structures (gems) between SMN1-MSCs and MSCs derived from normal human iPSCs (h-MSCs). These findings provide a novel strategy for obtaining gene-targeted MSCs for potential clinical applications in autologous cell-based therapy.
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This work was financially supported by grants from the National Natural Science Foundation of China (81400928, 81271944, and 81272540), the National Key R&D Program of China (2016YFC0905100) and the Fundamental Research Funds for the Central Universities of Central South University (2016zzts168).
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The authors declare that there are no conflicts of interest.
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Feng, M., Liu, C., Xia, Y. et al. Restoration of SMN expression in mesenchymal stem cells derived from gene-targeted patient-specific iPSCs. J Mol Hist 49, 27–37 (2018). https://doi.org/10.1007/s10735-017-9744-1
- rDNA locus
- Gene targeting