Asian Scientist (Oct. 23, 2013) – Scientists in Japan have succeeded in directly converting human skin fibroblasts into induced chondrogenic (iChon) cells required for cartilage regeneration therapy.
Articular cartilage, which is made up of chondrocytes and extracellular material, functions in ensuring smooth joint movement and absorbing shocks. Cartilage has little regenerative capacity and is gradually lost due to injury, aging, and other factors.
In their research, the scientists focused on using a genetic reprogramming strategy to convert fibroblast cells directly into chondrogenic (cartilage-forming) cells as a means of replacing lost cartilage.
The research team from the Center for iPS Cell Research and Application (CiRA) in Kyoto University had in 2011 reported the successful reprogramming of mouse dermal fibroblasts into iChon cells by means of inserting two reprogramming factors (c-MYC and KLF4) and one cartilage factor (SOX9) into the fibroblast cells.
In the new study, published in PLOS ONE, the team confirmed that it is possible to directly generate human iChon cells by inserting the same three factors into human dermal fibroblasts. The iChon cells 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 cartilage tissue, and no formation of teratomas or other tumors was observed for three months after the iChon cells were transplanted.
Although the study shows that direct reprogramming of fibroblasts into chondrocytes is possible in human cells, modifications have to be made before it can be safely used for human cartilage regeneration therapy. This is because the method used by the researchers involves the insertion of c-MYC, a well-known cancer gene, into fibroblasts. Furthermore, a retrovirus is used to introduce the factors, raising significant safety concerns.
Nevertheless, the researchers hope that the technique developed in this study will represent one option for supplying high-purity chondrocytes for cartilage regeneration, and that it will contribute to elucidation of the pathology of cartilage-related diseases.
The article can be found at: Outani et al. (2013) Direct Induction Of Chondrogenic Cells From Human Dermal Fibroblast Culture By Defined Factors.
Source: Center for iPS Cell Research and Application (CiRA).
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