Tiny, the Mouse, Takes a Giant Step for Mankind

You’ve probably heard of Dolly the sheep, the world’s first cloned mammal. But you’ve probably never heard of Tiny the mouse…one of the first creatures ever created from “reprogrammed” adult cells.

Let me introduce you. That’s him in the picture below.

"Tiny" the Mouse

Don’t be fooled by this little mouse’s name, what Tiny represents in the world of regenerative medicine is anything but tiny…

In July 2009, a team from the Beijing’s Institute of Zoology reported in the journal Nature that it created healthy, fertile animals (Tiny and its brethren) by using so-called pluripotent stem cells (iPS). IPS cells are adult cells that have been genetically reprogrammed back to a pluripotent state. A pluripotent cell is simply a cell that can become most or all of the 200 cell types of the body.

Tiny was one of dozens of mice created from iPS cells and born to a surrogate mother. At first, this amazing story generated renewed concern about human cloning, but the lead author of the paper, Qi Zhou, explained to Nature News that his research was “an important model for understanding reprogramming. … [but] not intended to be a first step towards using iPS cells to create a human being.”

When “embryonic stem cell therapy” exploded into the public vocabulary a decade ago, it instantly became an emotionally charged and politically divisive issue. Although hailed as having the potential to cure myriad diseases, the creation of embryonic stem cells involved the destruction of embryos. Therefore, many people, including then-President Bush, objected on moral grounds. Bush banned federal funding for research into embryonic stem cells in 2001. Eight years later, in March 2009, President Barack Obama lifted the ban. But the controversy remained.

That’s one of the reasons why iPS cells are so appealing. They are NOT derived from embryonic cells, but rather sourced from living adult individuals, and thus, don’t raise ethical issues. IPS cells are generated from adult “somatic” cells harvested from skin, blood or fat tissue.  Some genes that are turned on (or expressed) in embryonic stem cells are silenced (or turned off or not expressed) in mature adult cells. To create iPS cells, the silenced genes are reintroduced into the adult cells so that the cells are back-programmed to behave like embryonic stem cells.

Dr. Qi Zhou and his team used a virus to deliver four genes into fibroblast cells taken from adult mice, triggering the change to iPS cells. They then implanted the cells into an embryo that didn’t have the requisite genetic information for it to develop beyond a placenta. That these implanted embryos developed into full baby mice proved that iPS cells could indeed do all the work of natural embryonic stem cells.

Tiny’s birth demonstrated that iPS cells are so similar to embryonic stem cells in their identity that they are capable of embryonic development. The teeny mouse is in fact a huge scientific breakthrough that opens up amazing perspectives for stem cell research.

Because of their great developmental plasticity, iPS cells can revolutionize the field of regenerative medicine. They already are a powerful predictive tool used in an increasing number of research laboratories all over the world to study mechanisms behind various diseases. They also have a potential value for discovery of new drugs and establishment of cell therapy protocols.

It is not surprising that the prestigious journal Nature Methods named iPS cells “method of the year 2009.”

Since iPS cells are reprogrammed to behave like embryonic stem cells, they have potentially the same plasticity. Therefore, iPS cells have the ability to generate all cell types found in the body. Human iPS cells have been differentiated (or transformed) in vitro into a variety of specialized cells, including adipocytes, cardiomyocytes, primitive hematopoietic cells, pancreatic beta-cells, and several different neuronal cell types.

Potentially, therefore, iPS could produce a variety of cell types that could repair any damaged tissue. By implanting certain iPS cells, organs affected by illness or injury would have a chance at healing or regenerating themselves. This kind of therapy could help increase the operational functions of a damaged organ and therefore, heal very debilitating injuries or diseases.

Encouraging results have been achieved in laboratory animals using iPS to alleviate symptoms from lateral amyotrophic sclerosis, diabetes mellitus type III, Gaucher disease, Duchenne and Becker muscular dystrophy, adenosine deaminase deficiency combined with severe immunodeficiency, Shwachman-Bodian-Diamond syndrome, down syndrome, Parkinson and Huntington disease and many others.

And to repeat; iPS cells are NOT embryonic stem cells. This distinction is not merely a moral one; it is also an important scientific one. Because iPS stem cells derive directly from each patient, they possess one very key advantage.  They don’t trigger the “immune rejection” reactions that plague so many transplantation therapies.

As such, iPS cells offer the promise of patient-specific therapies. In other words, it may be possible to create a kind of personalized regenerative medicine that does not trigger immune rejection.

In the future, a patient that needs a tissue replaced could go to the clinic and have a piece of skin removed. In a culture dish, his own skin cells would be genetically reprogrammed to regress into the pluripotent state of iPS cells. The patient’s iPS cells could then be differentiated (or developed or transformed) into whatever tissue was problematic and the newly generated tissue could be transplanted back into the patient.

iPS cells are regarded as the most promising way to create stem cells for regenerative medicine. iPS cells technology should eventually make cell transplantation therapies possible for a wide variety of diseases and injuries, while circumventing ethical and immune rejection challenge…

And you thought the birth of a teeny Tiny mouse was not a revolution?!


Severine Kirchner, PhD
for The Daily Reckoning