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Cytokine directed chondroblast trans-differentiation: JAK inhibition facilitates direct reprogramming of fibroblasts to chondroblasts.
Cells 9:191 (2020)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Trans-differentiation ; Osteoarthritis ; Cartilage Regeneration ; Cellular Reprogramming; Pluripotent Stem-cells; Chondrocyte Differentiation; Direct Conversion; Chondrogenesis; Expression; Mouse; Cardiomyocytes; Pathway
ISSN (print) / ISBN
2073-4409
e-ISSN
2073-4409
Journal
Cells
Quellenangaben
Volume: 9,
Issue: 1,
Article Number: 191
Publisher
MDPI
Publishing Place
Basel
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