At first glance the naked mole rat (NMR), or Heterocephalus glaber to his Latin speaking friends, might not win you over with its looks, but it truly is an amazing animal. It’s obviously comfortable in its own skin, but it also thrives in harsh environments, lacks pain sensitivity in its skin, has low metabolic and respiratory rates, and most interestingly of all, is highly resistant to cancer.
This has piqued the interest of more than a few scientists, who study these extraordinary animals in the hopes of revealing the anti-cancer mechanisms that they possess.
Among this group are researchers from the laboratories of Hideyuki Okano (Keio University School of Medicine, Tokyo, Japan) and Kyoko Miura (Hokkaido University, Japan), who recently sought to generate NMR induced pluripotent stem cells (NMR-iPSCs).
Why, we hear you asking? iPSC reprogramming and cancer development have many parallels, which is why we worry about the potential for tumorigenicity in cell therapies using transplanted iPSC-derived cells.
Their new study, published in Nature Communications, aimed to generate and study naturally cancer-resistant NMR-iPSCs, in the hope of uncovering a means to make safer human iPSCs therapies .
This new study demonstrated:
- Generation of NMR-iPSCs via the retroviral transduction of the Oct4, Sox2, Klf4, and Myc reprogramming factors in NMR skin fibroblasts.
- Resultant cells displayed pluripotent characteristics.
- While human and mouse iPSCs formed teratocarcinomas following injection into the testes in an immunodeficient mouse model, NMR-iPSCs engrafted in the testis without forming tumors.
So what gives NMR-iPSCs their tumor resistance?
- Gene expression profiling revealed the NMR-iPSC-specific activation of the ARF tumor suppressor and the presence of a disrupting mutation in the tumor promoting ERAS oncogene.
- Interestingly, overexpression of Arf in mouse iPSCs (normally repressed) reduced tumorigenic capacity.
The researchers hope that their underground scrabblings (read – lab work) will lead to the production of non-tumorigenic human-iPSCs and safer iPSC-based therapies.
More mole-cular analyses of NMR-iPSCs may rat-ify these exciting findings, but for now, inform yourself with the naked (mole rat) truth over at Nature Communications, May 2016.