Main Category: Stem Cell Research
Also Included In: Bones / Orthopedics
Article Date: 18 Oct 2013 – 0:00 PDT
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Center for iPS Cell Research and Application – Kyoto University
“Direct Induction of Chondrogenic Cells from Human Dermal Fibroblast Culture by Defined Factors ” Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, et al. (2013) Direct Induction of Chondrogenic Cells from Human Dermal Fibroblast Culture by Defined Factors. PLoS ONE 8(10): e77365. doi:10.1371/journal.pone.0077365
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Human dermal fibroblast culture enables direct induction of chondrogenic cells
Normal articular cartilage consists of hyaline cartilage, but when this is lost it is partially replaced by fibrous cartilage. Fibrous cartilage produces Type I collagen and loses the extracellular material structure specific to cartilage. To restore cartilage function, this means that either high-purity hyaline cartilage not containing fibrous cartilage must be prepared and transplanted into the site where cartilage has been lost, or fibrous cartilage must be converted in situ into hyaline cartilage.
In 2011, Professor Tsumaki and his team reported that, by inserting into mouse dermal fibroblasts two reprogramming factors (c-MYC and KLF4) and one cartilage factor (SOX9), they had achieved direct reprogramming into induced chondrogenic cells without passing through an iPS cell stage. In the present study, the team confirmed that, by inserting the same three factors (c-MYC, KLF4, and SOX9) into human dermal fibroblasts, it was possible to directly generate iChon cells. The iChon cells had lost the gene pattern specific to fibroblasts and instead displayed the gene pattern of chondrocytes. Additionally, when the iChon cells were transplanted to immunodeficient mice, they generated hyaline cartilage tissue, and no formation of teratomas or other tumors was observed for three months after the iChon cells were transplanted.
Another application of direct reprogramming is to carry out direct reprogramming of fibrous cartilage into hyaline cartilage in vivo. For this purpose, scientists will need to develop a technology to induce local reprogramming around cartilage tissue that avoids gene transduction, for instance by using chemical compounds instead. Going forward, a careful distinction will need to be drawn in applying the two methods – use of the iPS cell stock and use of the direct reprogramming method.
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Articular cartilage, which is made up of chondrocytes and extracellular material in the form of Type II, Type IX, and Type XI collagens and aggrecan, fulfills the functions of ensuring smooth joint movement and absorbing shocks. Cartilage has little regenerative capacity and is gradually lost due to injury, aging, and other factors.
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