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Article

Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene

  • Authors:
    • Baofeng Li
    • Ying Zhang
    • Mei Li
    • Xiaoliang Zhao
    • Huibin Xie
    • Xiaoze Guo
    • Fei Wang
    • Hong Xia
    • Bei Chen
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
  • Pages: 2397-2405
    |
    Published online on: January 30, 2018
       https://doi.org/10.3892/ijmm.2018.3442
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Abstract

Stem cells and other associated cell types may be a potential alternative to treat various genetic disorders that currently do not benefit from traditional approaches. Functional recovery of cells could be induced via directional differentiation or genetic manipulation. In this study, mesenchymal stem cells (MSCs) were obtained from a patient with osteoarthritis (OA) carrying a functional single‑nucleotide polymorphism (SNP rs143383, C/T transition) within the 5'‑UTR of growth and differentiation factor 5 (GDF5) gene. The SNP causes GDF5 expression to be reduced and thus increases OA susceptibility. Aiming to correct the dysfunctional gene, a pair of transcription activator‑like effector nucleases (TALENs) were designed to cleave the DNA around the mutated locus, coupled with a short single stranded DNA complementary to the cleavage site. Following in vitro cell colony formation and selection, two genetically corrected MSC colonies were identified out of a total of 142. These MSCs were induced and differentiated into chondrocytes. As a result, genetically corrected chondrocytes exhibited normal morphology and lower levels of apoptosis compared with cells carrying the SNP. In cultured cells, the secretion of matrix metalloproteinases was suppressed and TIMP metallopeptidase inhibitor 1 was increased by correction of the mutation. Furthermore, the expression of GDF5 target genes, cell vitality‑associated genes and extracellular matrix degrading genes were returned to normal levels in corrected cells compared with mutation‑carrying cells, indicating the functional recovery of these corrected chondrocytes. The present study demonstrated that TALEN‑mediated genetic correction can be used to edit genes in adipose‑derived MSCs from patients with OA and may have clinical potential.
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Copy and paste a formatted citation
Spandidos Publications style
Li B, Zhang Y, Li M, Zhao X, Xie H, Guo X, Wang F, Xia H and Chen B: Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene. Int J Mol Med 41: 2397-2405, 2018.
APA
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X. ... Chen, B. (2018). Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene. International Journal of Molecular Medicine, 41, 2397-2405. https://doi.org/10.3892/ijmm.2018.3442
MLA
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X., Wang, F., Xia, H., Chen, B."Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene". International Journal of Molecular Medicine 41.4 (2018): 2397-2405.
Chicago
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X., Wang, F., Xia, H., Chen, B."Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene". International Journal of Molecular Medicine 41, no. 4 (2018): 2397-2405. https://doi.org/10.3892/ijmm.2018.3442
Copy and paste a formatted citation
x
Spandidos Publications style
Li B, Zhang Y, Li M, Zhao X, Xie H, Guo X, Wang F, Xia H and Chen B: Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene. Int J Mol Med 41: 2397-2405, 2018.
APA
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X. ... Chen, B. (2018). Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene. International Journal of Molecular Medicine, 41, 2397-2405. https://doi.org/10.3892/ijmm.2018.3442
MLA
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X., Wang, F., Xia, H., Chen, B."Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene". International Journal of Molecular Medicine 41.4 (2018): 2397-2405.
Chicago
Li, B., Zhang, Y., Li, M., Zhao, X., Xie, H., Guo, X., Wang, F., Xia, H., Chen, B."Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene". International Journal of Molecular Medicine 41, no. 4 (2018): 2397-2405. https://doi.org/10.3892/ijmm.2018.3442
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