Editors' ChoiceStem Cells

Power of the Young—New Stem Cell Source for Treating Autoimmune Disease

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Science Translational Medicine  18 Jun 2014:
Vol. 6, Issue 241, pp. 241ec107
DOI: 10.1126/scitranslmed.3009596

Autoimmune disorders—including multiple sclerosis, rheumatoid arthritis, and type I diabetes—are a growing public health concern and directly impact 5 to 10% of the U.S. population. Human mesenchymal stem/stromal cells (hMSCs), typically derived from adult bone marrow or adipose tissue, have emerged as a promising cellular immunotherapeutic and are currently being tested in a plethora of clinical trials worldwide. Despite their classical role as stem cells for connective tissues (bone, cartilage, and fat), hMSCs are also surprisingly capable to migrate to sites of injury and inflammation, where they stimulate endogenous tissue repair through a variety of paracrine and immunosuppressive effects. However, these properties of adult-derived hMSCs vary greatly from donor to donor and are often lost after in vitro expansion to the numbers required for clinical efficacy in human patients. Now, Wang et al. provide evidence that human embryonic stem cells may be a more potent and scalable source of hMSCs for clinical testing in autoimmune disorders.

In the current study, the authors used a standard mouse autoimmune disease model, experimental autoimmune encephalomyelitis (EAE), which reflects some of the T cell–mediated autoimmunity seen in multiple sclerosis patients. They demonstrated that hMSCs derived from four independent human embryonic stem cell lines and systemically delivered to EAE mice all exhibited potent therapeutic properties, including decreased disease severity and inflammatory activity in the central nervous system. The authors’ major advance was showing that the human embryonic stem cell–derived hMSCs exhibited more potent and consistent immunosuppressive and regenerative properties in the EAE mice as compared with six independent hMSC isolates from adult tissues.

Given the extensive clinical safety data already available for adult-derived hMSCs, it is likely that human embryonic stem cell–derived hMSCs will rapidly progress to clinical testing for human autoimmune disorders. However, before this, it will be important to more thoroughly understand the differences between adult and human embryonic stem cell–derived hMSCs and to extend preclinical studies to additional models of human autoimmune diseases. Moreover, the direct comparison of adult-derived and human embryonic stem cell–derived hMSCs is somewhat confounded by genetic variation between the cells. Future studies with human induced pluripotent stem cell–derived hMSCs may provide a more accurate isogenic comparator to adult-derived hMSCs.

X. Wang et al., Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis. Stem Cell Rep., published online 5 June 2014 (10.1016/j.stemcr.2014.04.020). [Full Text]

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