A New Era for Disease Modeling and Drug Screening
December 29, 2008
Induced Pluripotent Stem (iPS) cells are cells that have been reprogrammed from skin fibroblasts back to a state reminiscent of Embryonic Stem (ES) cells. Human iPS cells were first discovered back in November 2007 by pioneer Dr. Shinya Yamanaka at Kyoto University (reported in scientific journal Cell in November 2007). iPS cells are thought to hold the same potential as ES cells in regenerative medicine such as disease modeling, drug screening, and cell replacement therapy, but with additional advantages as it bypasses the ethical issues relating to the use of human embryos.
Cancer Stem Cells: Fact or Fiction?
December 26, 2008
In the 1960s there was an unethical experiment where physicians took cancer cells from various types of malignancies and re-injected these cells back into the original cancer patient or another non-cancerous terminally ill patient.i The results from this experiment suggested that those with cancer lacked immunity to the disease while “healthy” individuals carried some immunity to the cancer cells. However, another interesting observation was made throughout the experiments: that it requires millions of cancer cells to initiate the growth of a tumor. It is this observation from which two theories emerged in the decades to come regarding tumor initiation and maintenance.
Returning home…
December 20, 2008
My blog this month is about returning home. I am an ex-pat Australian working in stem cell research at SickKids. I left Australia on Australia Day 2004 as a fresh-faced PhD graduate. Nearly 5 years have passed and I have returned this month for a brief trip in the capacity of both a mature researcher and as an aunty to see my kids for Christmas.
I won’t lie; the past few months have been interesting for me as I struggled to put all of my emotions in perspective. I have been full of joy and happiness, a little anxious and fearful, but proud as well, which has made for some very interesting internal dialogues! It took a little time to realise these feelings were not about my return home after so long away, but rather they are indelibly linked to life as a researcher, regardless of the stage at which we find ourselves in our careers.
I am at the point in my career where I am almost ready to strike out for independence, and I came home to look at research opportunities. My search started with giving a seminar to my home institution; that is to those responsible for giving me my foundations in science. This seminar was important to me as much for showcasing the stem cell research we are doing at SickKids with respect to childhood cancer as it was for showing that living abroad and working in an environment that fosters collaborative efforts, as SickKids does, has been a great developmental opportunity. I was able to illustrate that as a result of the information we have gained from the cancer stem cell research we are doing we could offer insight into why current therapies are not working, the mechanisms of responsible for patient relapse at distant metastatic sites, and how we might treat them in the future.
I was fortunate to give this seminar to a second children’s research institute and talk to more Australian scientists about the stem cell research being done at SickKids and to some other scientists interested in finding out what we are doing at SickKids. The response to my research in the role of cancer stem cells in children’s cancer was incredibly positive for both the application of stem cell research theories to children’s cancer, particularly a cancer where distant metastases are common and responsible for a majority of deaths, as well as the collaborative efforts of the team (the ward, pathology, surgery, clinic, and research) at SickKids as model system.
Stem cell research is an interesting research area in so many ways, but none more interesting for me at this stage in my career as I look for the right place to settle and establish myself as a stem cell researcher. SickKids have put me in the right place with respect to being competitive in attracting career offers and research funds to continue my efforts in trying to understand the role of cancer stem cells in childhood cancer.
I am happy about my experience of returning home to tell my very early career mentors about how I have developed as a scientist since I left them, and have made some really tough career and life decisions in this too short a trip. I’d like to continue this blog to tell you all about the process a young scientist goes through to make the decision to become an independent researcher and to tell you about the process of looking for the right job.
Talk to you next month and Merry Christmas!
Luck
December 16, 2008
I had a very lucky week; I was hit by a car.
Last Tuesday night I was walking along a busy downtown street. As I crossed the intersection, a car sped around the corner, struck me, and threw me to the ground. Just a moment before I was hit, I saw the headlights of the car only inches from my knee. Amazingly, the Hollywood clichés about time slowing down seem true. As I was hit, many thoughts went through my mind as if the impact was occurring in slow motion. I thought, “but the light isn’t even yellow, why is the car here in the crosswalk”? Then, “boy, it’s lucky this isn’t a big truck with those steel cages on the front”. I even thought, “damn, this is going to hurt”. But, part of my mind was still a stem cell biologist as I thought, “I hope I don’t snap my spine, because stem cell transplants are not ready yet."
Principles of Responsible Translational Stem Cell Research
December 15, 2008
The recent surge of interest in stem cell research has fuelled the hope for a future where today’s discoveries have been translated into patient treatments or cures. A tricky question is how do we know when that future has arrived? When has enough basic research been done to justify clinical trials in human patients and how do we know when enough trials have been done, and the benefits and risks are clear enough, that stem cell therapies can pass clinical trials and be made available to everyone?
For Cars or Cures?
December 9, 2008
Food for Thought… what if we invested $40 billion into scientific research!?
The US and Canadian automotive sectors are lobbying their governments for $34 billion (US), and $6 billion (CAN) respectively. 40 BILLION dollars all tolled!! And it’s looking like they’re going to get it.
Did you know that the yearly budget for the National Institute for Health (NIH) is $28 billion? Did you know that this amount of money supports “325,000 researchers at over 3,000 universities, medical schools, and other research institutions in every state and around the world”? The predicament in Canada is even more staggering! The total expenditures of the Canadian Institute for Health Research (CIHR) for 2007-08 were less than $1billion: SIX-TIMES LESS than the must-have-to-survive package the Canadian automakers are begging for!
The International Society for Stem Cell Research warned against fraudulent clinics and treatments
December 4, 2008
The International Society on Stem Cell Research has released Guidlines for the Clinical Translations of Stem Cellsl that examine the scientific, clinical, regulatory, ethical and societal issues that must be addressed to ensure that basic stem cell research is responsibly transitioned into appropriate clinical applications.
Read more about these guildlines here and here. Also, have a look at Ian Clarke’s blog post from Monday about this very issue.
The Power of Hope
December 2, 2008
I want to discuss the power of hope. I recently read an article in a national newspaper about a family who was traveling to China to receive stem cell therapy to restore their child’s vision. This child had been born blind as a result of a developmental defect that results in the optic nerve failing to develop normally. As a research scientist who studies brain stem cells and cancer stem cells, I was surprised to learn that hospitals in China were offering stem cell treatments to patients. The stem cells that generate the eye and optic nerve are very similar to the brain stem cells that I study. In this case, the first reports to suggest that this therapy may work came just within the last few years in studies on rats and mice.
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.
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”
Some of our experts
Stem Cell Origins
Cancer stem cells
Stem Cells and the Nervous System
