Of mice and (hu)men…
November 28, 2008
What do mice and humans have in common? It turns out…a heck of a lot. In fact, humans and mice have quite a few common genes that play similar roles in the development of our major organ systems, including nervous, cardiovascular, immune, skeletal, and endocrine to name a few. Moreover, the cells of mice and men are so similar that we can interchange genes between mice and humans quite frequently, and we can introduce genetic alterations into mouse cells found in human disease and observe the consequences.
One of the most common ways to study mammalian development and diseases such as cancer and other genetic disorders is to modify the mouse genome and then study the effects of these modifications. One advantage is that mice have short life spans and reproduce extremely quickly, as frequently as every nine or so weeks. This provides researchers with a tool to study these effects over many generations and allows us to understand development and disease from the beginning, and not solely at their endpoints.
Various types of mouse models exist for a plethora of diseases from cancers to genetic disorders such as Huntington’s and Alzheimer’s disease, to behavioural disorders such as anxiety and alcoholism. There are several ways to create these mice; you may ‘knock-in’ a gene, alter a gene, or ‘knock-out’ a gene. All of these methods require that the gene of interest be modified in the mouse embryonic stem cells so that the subsequent mouse that develops carries the modification in every cell. The resulting phenotype (a fancy scientific word for characteristic) may resemble the symptoms of human disease and thus may be used as a model for treatment discovery.
How does this apply to stem cells, other than the brief cameo of embryonic stem cells just mentioned? Well, if we suspect certain genes to be important in stem cell regulation in various tissues, we can then manipulate these genes and study the effects on stem cells in the mouse, answering questions about tissue and organ development, tumour initiation, and diseases that are thought to arise from stem cell populations gone wrong.
One of the best ways to understand human disease is to transplant human cells into mice. These experiments require special mice that have been bred to lower or eliminate their immune system (like the bubble-boys of mice), essentially allowing them to host human cells without mounting an immune attack on the cells. Using these mice, researchers around the world were able to prove the isolation of cancer stem cells (including brain cancer stem cells!!), understand major genetic alterations associated with human cancers, and test chemotherapeutic agents against human cancer tissues as a preliminary step to clinical trials.
That said the genetics behind human diseases are generally far more complex. However, thanks to mice, we’ve made great strides in understanding our development, how and why we succumb to disease and what we can do to treat it. So next time you see a mouse scurry across your floor, offer it cheese…they’ve earned it!
Stem cells used to seed trachea transplant
November 26, 2008
In a recent report published in the medical journal The Lancet, European researchers detailed their success in transplanting a trachea, seeded with the patient’s own stem cells, to restore breathing function to a young Columbian woman named Claudia Castillo (left). This discovery is noteworthy because it marks the first time a patient’s own stem cells were used in the reconstruction of their airway. Since the patient’s own cells were used, complications that arise from immune system rejection of the donated tissues were avoided.
“A whole new vista”
November 21, 2008
SickKids stem cell researchers were featured in today’s Toronto Star
Last November, two teams of scientists announced they had found a way to coax human skin cells to act like embryonic stem cells, which are capable of becoming any tissue.
Scientists crowed after hearing the news, likening the discovery to the Wright brothers’ first flight.
Not only did it sidestep the ethical concerns dogging the field – the technique does not use human embryos or controversial cloning techniques – the finding brought scientists closer than ever to the long-awaited promise of personalized organ and tissue transplantation.
That excitement has continued unabated. Hundreds of scientists around the world have now adopted the "reprogramming" technique. Many hope to use the cells, called induced pluripotent stem cells, or iPS cells, to learn about – and learn to cure – diseases.
And Toronto, already a hub of stem-cell activity, is leading the way.
For the full article, please click here
The future of genomics
November 14, 2008
This week Craig Venter visited SickKids and gave the keynote address at the annual SickKids research symposium. Whereas the majority of scientists toil in relative obscurity, Dr. Venter is one of the rare scientists whose work and ideas are so highly cited in the popular media that if someone doesn’t recognize his name, they almost surely have heard about his work. In 1998, Dr. Venter founded Celera Genomics and used the tools and techniques that the company developed to successfully sequence and publish the human genome in February 2001. He and his team at Celera also sequenced the fruit fly, mouse and rat genomes.
As Dr. Venter detailed during his hour long lecture, the sequencing of the human genome was hardly the pinnacle of his work, but rather a springboard to rapidly expand further research. Dr. Venter now leads the Craig J. Venter Institute (http://www.jcvi.org), a multidisciplinary genomic-focused organization with more than 400 scientists and staff.
The work that the Venter Institute is doing, some of which is done through collaborations with genomics researchers here at SickKids, is providing an unprecedented level of understanding of how individual organisms and individual people differ at the molecular level. This is laying the groundwork for what many regard as the future of health care, personalized medicine, where an individual’s preventative measures or treatment options are tailored to their unique risk factors and biology.
Not all of their current work is human-centric though, one of the more fascinating projects that caught my attention was their interest in cataloguing the diversity of life in the oceans. To do this, Dr. Venter’s group covered over 32 000 nautical miles of ocean, obtaining water samples which were later used for harvesting and sequencing of microbial DNA. This work led to the discovery of over 6 million new genes, a biological resource that we haven’t even begun to utilize. Over the years, we will be moving rapidly towards understanding what each of these genes do, how they affect the metabolism of an organism, and how they can be utilized to improve our environment by optimizing biological processes such as chemical degradation or energy production.
The rapidly expanding field of genomics impacts on every aspect of the biological and medical sciences, and indeed impacts society as a whole. Similar to stem cell research, as our technical capabilities increase, there must be a coincidental increase in the level of discussion of how we as a society would like to pursue these technologies, regulate their use, and ultimately utilize their potential for the betterment of human health and the natural environment.
How to Reboot the Human Body: from Maclean’s Magazine
November 13, 2008
Ontario IPS Cell Facility highlighted in Maclean’s Magazine
The Ontario IPS Cell Facility at SickKids was profiled in the October 30 issue of Maclean’s magazine. Connecting for Kids blogger Aaron Cheung, SickKids Cheif of Research, Dr. Janet Rossant and other stem cell staff at SickKids were featured in the article.
Rett Syndrome and induced Pluripotent Stem cells goes “Green”
June 17, 2009 by Aaron Cheung
Stem cell researchers at The Hospital for Sick Children have now devised a method, reported in the scientific journal Nature Methods, that will facilitate the generation of induced Pluripotent Stem (iPS) cells. I have previously blogged about the promise of iPS cells (see related articles). iPS cells are cells which have been reprogrammed from a differentiated somatic cell (such as your skin cells) to a pluripotent stem cell (like an embryonic stem cell, only that you don’t need to use embryos!). The generation of iPS cells is inherently very rare which occurs at a frequency of about 0.01% meaning you can generate about one iPS cell line out of hundred thousand cells. Out of which, many lines fail to satisfy the different rigorous tests necessary to be given the prestigious name of “iPS cell”.
Continue reading Rett Syndrome and induced Pluripotent Stem cells goes “Green”
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