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Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors
Date:10/19/2013

n 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 (Fig. 1). 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 (Fig.2), and no formation of teratomas or other tumors was observed for three months after the iChon cells were transplanted.

The present study demonstrates that direct reprogramming of fibroblasts into chondrocytes is also possible in human cells. Because the method used in the study makes use of c-MYC, which is thought to have a major role in tumorigenesis, and because it employs a retrovirus to introduce the factors, it could not be applied without modification in human therapy.

To produce chondrocytes for cartilage regeneration, CiRA also has the option of using the iPS cell stock which it is now engaged in building. Using the iPS cell stock would involve not autologous transplantation but isogeneic (allogeneic) transplantation, and rejection reaction and other risks would therefore need to be considered, but it would also have major cost benefits.

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.

The researchers hope that the technique developed in this study will represent one option for supply of high-purity chondrocytes for cartilage regeneratio
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Contact: Akemi Nakamura
cira-pr@cira.kyoto-u.ac.jp
81-753-667-000
Center for iPS Cell Research and Application - Kyoto University
Source:Eurekalert  

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