Editors' ChoiceTissue Engineering

Playing Without Pain—Or Tumors

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Science Translational Medicine  17 Mar 2010:
Vol. 2, Issue 23, pp. 23ec44
DOI: 10.1126/scitranslmed.3001046

Sports legends often regale fans with stories of Herculean feats accomplished while nursing serious injuries, but there are many more tales of career-ending traumas, especially when the damage won't heal. Certain types of common cartilage injuries, for example, have a hard time healing because of the tissue's lack of a blood supply. Stem-cell therapies have the potential to revolutionize tissue repair and regeneration. But embryonic and adult stem cells implanted in vivo can grow uncontrollably and give rise to tumors. This risk is a stern obstacle in the path of translational stem cell research and its transition from the bench to widespread clinical use. Now, Akay et al. show that differentiating bone-marrow mesenchymal stem cells (MSCs) before in vivo implantation dramatically reduces their tumor-inducing ability as compared with that of undifferentiated MSCs.

MSCs are multipotent and can differentiate into chondrocytes, cells that make the collagen-rich cartilage matrix. Using the cytokine transforming growth factor–β1 (TGF-β1) and the steroid hormone dexamethasone, the authors differentiated mouse MSCs into chondrocytes in vitro and then co-implanted either the differentiated or undifferentiated stem cells with melanoma cells into a mouse model. The melanoma cells—which were from a genetically distinct donor and normally would not form tumors in these mice because of host rejection—were implanted 3 cm away from the site of (differentiated or undifferentiated) stem-cell implantation. Akay et al. found that tumors formed in the mice as a result of the immunosuppressive ability of stem cells. But growth of the cancer was reduced by two-thirds in mice that housed the differentiated MSCs as compared with that of mice carrying the undifferentiated counterparts. Furthermore, mice that received differentiated MSCs had no occurrence of metastases, with the cells remaining only at the implantation site. In contrast, all mice receiving the undifferentiated MSCs developed metastatic cancer, with the implanted cells spread throughout their bodies 2 weeks after cell implantation. The new insights from Akay et al. suggest a way to limit cancer risk during stem cell–based cartilage repair—which might pave the way to a timely return to the tennis courts.

I. Akay et al., Tumor risk by tissue engineering: Cartilaginous differentiation of mesenchymal stem cells reduces tumor growth. Osteoarthri. Cartilage 18, 389–396 (2010). [Full Text]

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