Abstract
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.
Highlights
Osteoarthritis (OA) is a consequence of the degeneration of hyaline articular cartilage, which leads to the formation of fibrocartilage
We propose that trans-differentiation of patient fibroblasts to chondroblasts provides a shorter path for cartilage repair
Rex1 was highly expressed at every time point under the induced pluripotent stem cells (iPSCs) condition and significantly (p = 0.0001) higher on day 6 when compared to the trans-differentiation group (−leukemia inhibitory factor (LIF)+JI1) (Figure 1e). These results indicated that LIF removal, combined with the JI1 addition, avoided intermediate iPSC formation
Summary
Osteoarthritis (OA) is a consequence of the degeneration of hyaline articular cartilage, which leads to the formation of fibrocartilage. The most common approach is microfracture chondroplasty, which uses penetration of the subchondral bone to deliver non-chondroblast endogenous progenitor cells from the bone marrow into the defected area. Another method is autogenous osteochondral transplantation/mosaicplasty, which transfers autologous osteochondral grafts to the affected area. There is autologous chondroblast implantation performed after isolating chondroblasts from a piece of the cartilage of a small non-load bearing area of the knee joint. These cells are expanded in vitro and transplanted into the chondral defect [3]
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