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Open AccessArticle

Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

1
Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 1N4, Canada
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Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Health and Environment, 85764 Neuherberg, Germany
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Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
4
Faculty of Medicine University of Queensland. 20 Weightman St, Herston 4006, QLD, Australia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 191; https://doi.org/10.3390/cells9010191
Received: 17 December 2019 / Revised: 8 January 2020 / Accepted: 9 January 2020 / Published: 11 January 2020
(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)
Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. OSKM factors (Oct4, Sox2, Klf4, and cMyc) accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice. View Full-Text
Keywords: trans-differentiation; osteoarthritis; cartilage regeneration; cellular reprogramming trans-differentiation; osteoarthritis; cartilage regeneration; cellular reprogramming
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MDPI and ACS Style

Cota, P.; Helmi, S.A.; Hsu, C.; Rancourt, D.E. Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts. Cells 2020, 9, 191.

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