4.7 Article

Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts

Journal

SCIENTIFIC REPORTS
Volume 10, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-61071-6

Keywords

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Funding

  1. Fundacion Espanola de Reumatologia [PI16/02124, PI17/02197]
  2. Instituto de Salud Carlos III-General Subdirection of Assesment and Promotion of the Research - European Regional Development Fund (FEDER) A way of making Europe [PI16/02124, PI17/02197]
  3. Rede Galega de Terapia Celular and Grupos con Potencial de Crecemento
  4. Xunta de Galicia [R2016/036, R2014/050, CN2012/142, GPC2014/048]
  5. Deputacion da Coruna [BINV-CS/2015]
  6. University of A Coruna
  7. Centro de Investigacion Biomedica en Red-Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN)
  8. European Union (European Social Fund)

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Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA.

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