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Study uses skin cells to create cartilage in mice
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Researchers from Osaka University Graduate School of Medicine in Japan have used mouse skin cells to create cells resembling chondrocytes that produced cartilage when injected into mice.
The development could be an important step toward a therapy that would use a patient’s own skin cells to repair cartilage injuries, according to a press release.
The researchers used fibroblasts isolated from adult mouse skin, expressing proteins used to induce pluripotency along with a factor that promotes a chondrocyte fate. Their study was published in the Journal of Clinical Investigation.
The group reasoned that regeneration of cartilage might be possible if they could develop a method to generate new chondrocytes. That regeneration could serve as an answer to the challenging clinical issue of cartilage injury repair using hyaline cartilage.
Potential for hyaline cartilage
Due to a limited number of chondrocytes in vivo, as well as in vitro, de-differentiation of chondrocytes into fibrochondrocytes – which secrete type I collagen and have an altered matrix architecture and mechanical function – the researchers wrote of a need for a “novel cell source” that produces hyaline cartilage.
Working with the knowledge that the generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming of dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors, the researchers showed that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induced polygonal chondrogenic cells directly from adult dermal fibroblast cultures.
The group found that induced cells expressed marker genes for chondrocytes, but not fibroblasts. Although some induced cell lines formed tumors when subcutaneously injected into mice, other induced cell lines generated stable, homogenous hyaline cartilage-like tissue.
“Further,” the authors wrote, “the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous SOX9 and maintain chondrogenic potential after substantial reduction of transgene expression.”
“Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells,” they concluded.
Reference:
- Hiramatsu K. J Clin Invest. 2011. doi:10.1172/JCI44605.
Disclosure: The authors reported no financial disclosures.
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