Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts.
Perla CotaSummer A HelmiCharlie HsuDerrick E RancourtPublished in: Cells (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.
Keyphrases
- stem cells
- induced pluripotent stem cells
- cell therapy
- induced apoptosis
- single cell
- multiple sclerosis
- rheumatoid arthritis
- knee osteoarthritis
- extracellular matrix
- endoplasmic reticulum stress
- oxidative stress
- type diabetes
- high fat diet induced
- adipose tissue
- diabetic retinopathy
- bone marrow
- insulin resistance
- skeletal muscle
- drug induced
- pi k akt