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By Ariel Charney March 10, 2009

From Cell to Saviour

Newspapers, magazines and science journals have become inundated with talk of STEM CELLS, but as I squinted my eyes to look into the microscope at Dr. Pera’s lab at USC’s Zilkha Neurogenetic Institute, all I saw were tiny grey blobs of cells floating in a petri dish. I thought to myself, “were the real stem cells maybe in disguise?” It was hard to imagine what the hubbub was all about!

So why are stem cells so special?

However ordinary they may have seemed, these cells are anything but your typical cell. They have the ability to give rise to mature, functional cells of the body through a process called differentiation. In plain English, this means that a stem cell can become a brain cell, a liver cell, a pancreas cell, or any other kind of cell in the body. Think of the implications of that fact: it means that, in theory, stem cells could be used to create replacement, insulin-producing cells in diabetes patients, as well as replacement cells for other debilitating diseases such as Alzheimer’s, Parkinson’s, heart disease and even cancer.

Researchers are in an arms race trying to harness this powerful potential that lies within stem cells. Stem cells, indeed, are truly the future of a field called regenerative medicine. They provide a way of explaining how you develop from a fertilized egg to a walking, talking human being, as well as what may go wrong in that process.
It is easy to get carried away in how cool and wonderful all this may sound, but there are still many unanswered questions. What types of stem cells are out there, and what aspects of our understanding of stem cells are still in development?

Different types of stem cells have varied levels of potential (called plasticity) to turn (or morph) into other cell types. You might have read about embryonic stem cell research, which has been a controversial topic in the news. One of the reasons why embyonic stem cells are so valuable for research is their “pluripotency,” a characteristic that allows them to divide into virtually every type of cell in your body. (Adult stem cells are far less plastic.) However, here’s the catch— to isolate ESCs for culture, they need to be taken from a 3-4 day old human embryo, leftover from in vitro fertilization. This need is the central source of the ethical controversy around embryonic stem cell research. Nevertheless, these cells offer enormous potential and remain at the forefront of research. Once isolated from the embryos, they are cultured in a soup of growth factors and media that allow them to self-renew or that can coax them into differentiating into a particular cell type.

At Dr. Pera’s lab, research is focused on understanding the molecular pathways of ESCs in determining cell fate–that is, on understanding how ESCs decide what cell type to divide into. This includes isolating cells at different stages of differentiation, as well as investigating what genes are involved in the maintenance of pluripotency and how often those genes are expressed. Sure, you can transplant ESCs into a diseased organ, but how do you tell the ESCs what you want them to divide and differentiate into, or when you want them to stop dividing? Being able to control the self-renewal process and differentiation of ESCs is vital for future stem cell therapies.

As of yet there haven’t been any clinical trials using ESCS on humans for therapeutic purposes, but another type of stem cell called Adult Stem Cells (ASCs) have been used for more then 30 years in bone marrow transplants. ASCs are found in small numbers in almost every body tissue— yes, that even includes the brain! However, right now, researchers are trying to find better methods of identifying and isolating them. As mentioned above, ASCs, unlike ESCs, are only “multipotent cells,” meaning their differentiation is limited to a family of tissues. “Hemapoetic” stem cells, for instance, can only give rise to the cells of the blood. “Mesenchymal” stem cells can only give rise to connective tissue, blood vessels and lymphatic tissue. ASCs are usually triggered after cell damage or death; their role is to replenish the lost cells. Some ASCs, such as for hair or intestinal cells, which are regularly replaced, are always being called to renew lost cells. A number of diseases, such as leukemia, can compromise this renewal process, and this is where bone marrow transplants, to replace ASCs, are necessary.

Current ASC transplantation therapies, while sometimes quite successful, are nevertheless invasive and can be risky due to immune rejection, meaning, the body can reject the transplanted ASCs.

Can embryonic stem cells help with the problem of immune rejection?

When your body receives cells from a foreign system, your immune system’s automatic response is to attack it. However, if researchers could make ESCs with a genetic signature identical to yours, your body would not reject it. This task, of course, is not as easy as it sounds!

Those ‘grey blobs’ I was looking at are a very special type of stem cell at the forefront of solving this problem. In a way I was right in calling them ‘disguised’ or ‘fake’, since these are in fact artificially derived pluripotent stem cells, formally called Induced Pluripotent Stem Cells (iPSCs).  The procedure to make these “fake” stem cells was a success for the first time in 2007 and it involves taking skin cells (called “somatic” cells) and making them mimic ESCs, by getting the genes of the skin cells to express themselves in a similar pattern. This is done through a process called “transfection,” in which a virus, or its shell, anyway, called a “viral vector,” transports certain genes of interest into the nucleus of the skin cell. To see if the transfection was successful, the inserted vector contains a fluorescent gene, which can be viewed under a fluorescent microscope.

Although the transfection procedure had not entirely worked during my visit to USC, the MD/PhD student left my friend and I with some words of encouragement, “ Even negative results in science are important, as they can help guide you in a new direction.” In a field like stem cell research, with so much potential yet so many unknowns, one has to be creative at coming up with solutions to solve the many unanswered questions.

I am thrilled to say my friend and I were offered a summer internship at USC’s Center for Stem Cells and Regenerative Medicine. You may wonder— Research during the summer, what is she thinking? However, as an aspiring doctor and researcher, I don’t think I could have asked for anything cooler than this!

Here is a link to their site: http://stemcell.usc.edu/

Acknowledgements

The photograph “Rose Thorn Macro” is by Colin, under CC BY-NC-ND 2.0

Comments

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    Jonathan

    March 20, 2009

    I found this article interesting because it taught me how scientists use embryonic stem cells to create many other types of cells: brain cells, liver cells, pancreatic cells and many other cells in our bodies.  These cells could be used for transplant and could save a patient’s life.  I also learned that in order to get the right cells to do the job, a 3 to 4 day embryo must be sacrificed.  This embryo could give cells with high plasticity-cells that can give many types of other cells. 

    There is an ethical debate on whether we are alloud to use stem cell research or not.  Can we sacrifice the life of a very young embryo to make transplants and save other people’s lives? The question to ask is if the embryo is a person.  If the embryo is a person, it has a right to live, and taking his right to live is called ‘murder’.  If it is not a person, then destroying it to get the stem cells we want should be no problem. (I can hardly find an answer to that question)

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    Lionel Sabbah

    March 2, 2010

    This article was very well put together. The author gave a very general overview of the stem cell research and managed to cover many aspects of the topic. I had already heard about stem cell research and its potential yet i still learned something from this article. I always knew that these cells were cultured in laboratories, yet i didn’t know where the came from in the first place. To my understanding, I thought they were actually created/engineered by scientist rather than being taken from a 3-4 day old embryo. After reading this, I was very concerned. I don’t really agree with this method of producing these cells. I know the implications of this research can help save live but I find that this is not the way to go. Taking these cells from an embryo is like stealing from someone who has no voice yet. Instead, I believe research should be focused on trying to find a way to create these cells from scratch. Only then can we explore the possibilities of this technology!

    Another interesting idea that has been risen in recent research in the use of stem cells in order to create body parts (ears, eyes, organs, etc…). This is a fascinating idea that can revolutionize the world. It would bring great help to many handicapped people throughout the world by making their lives easier!

    grin

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    AB

    March 5, 2010

    I really enjoyed this article. I liked that you didn’t act like you knew it all and that you were confused about why these cells were so great when they looked the exact same. I have heard about stem cell research but this article really taught me what they are and what they do in a clear, easy to understand way. While I think that these cells are the future of medicine and saving lives, I don’t know how I feel about them taking the cells from the embryo. I much prefer that they be created from somatic cells or even someday made in the laboratory. I’m glad I read this article and I plan on reading more articles on stem cells in the future.

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    David3523

    March 12, 2010

    Throughout this article I came across many interesting and relevant questions that I had not thought of before. I had a pretty good knowledge of stem cells and their differentiation but never really came to ask myself questions like; How ESCs decide what cell type they will divide into? Or how do we signal to these cells to stop splitting. This article helped me view stem cells in a more critical manner and drew my attention to results that may be soon found in Dr. Pera’s lab. 
    My attention was also drawn to the Induced Pluripotent Stem Cells (iPSCs). I found it fascinating to know how transfection takes place in skin cells.
    The MD/PhD student was a hundred percent right. I think that negative results are just as important as positive ones. They can eliminate possibilities and open other pathways and insights to research.
    Having volunteered in a neurology laboratory this past summer I can second your opinion and tell you that volunteering in a research lab during your summer is really cool! Being able to help forward research in the medical field and feeling like a part of something big is truly incredible!

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