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Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts
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Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts
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Journal Article
Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts
2020
Overview
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.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Cell Transdifferentiation - drug effects
/ Cellular Reprogramming - drug effects
/ Chondrogenesis - drug effects
/ Glycosaminoglycans - metabolism
/ Hyaline Cartilage - drug effects
/ Hyaline Cartilage - metabolism
/ Hyaline Cartilage - pathology
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Inhibitory postsynaptic potentials
/ Janus Kinases - antagonists & inhibitors
/ Kinetics
/ Plasmids
/ Protein Kinase Inhibitors - pharmacology
