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HSCs are responsible for keeping us alive by granting us an eternal supply of blood cells.  (Source: Microscopy Inc.)

Rice University bioengineers Oleg Igoshin (left) and Jatin Narula may have found the switch that tells HSCs when to differentiate and self renew.  (Source: Jeff Fitlow/Rice University)
Master regulator could allow for easy growth direction, organ creation

Scientists are racing towards a future vision in which humans can regrow failing organs and essentially obtain immortality.  Along the way, they're shooting for the more obtainable aim of curing a number of diseases (cancer, Alzheimer's, Parkinson's, and paralysis, to list but a few) using stem cells.

A critical problem though is how to direct stem cells to become the proper tissue type.  Within the human body, there are a rich variety of cells -- endothelial cells, muscle cells, blood cells, osteoblasts (bone), and nerve cells to name but a few.  At some point in the development of the human body, these cell lines were created by a biochemical signal which instructing stem cells to become the particular cell type.

Experimentalists at Cambridge University and Rice bioengineers Oleg Igoshin and Jatin Narula have examined one of these critical biochemical signals.  Based on a computer model developed at Rice and experiments at Cambridge, they believe that a trio of regulatory proteins known as the "Scl-Gata2-Fli1 triad" controls the differentiation of hematopoietic stem cells (HSCs), the self-renewing cells the body uses to make new blood cells.

In healthy adult humans, each day HSCs are responsible for the creation of 100 billion new white and red blood cells.  HSCs are also capable of "self-renewing" if the bone marrow is damaged.

The research at Rice delved into looking at the three regulatory proteins and developing an mathematical model for how they interacted with HSCs.  In their model, the proteins act as a bistable switch, with two states -- "replenish HSC" and "differentiate".  The system ignores extraneous signals and throws the switch only when a signal persisted.

Igoshin, an assistant professor in bioengineering at Rice, comments, "We don't yet have the experimental verification that this is the master-level regulator for HSCs, but based on our model, we can say that it has all the properties that we would expect to find in a master-level regulator."

Jatin Narula, a Rice graduate student, adds, "In examining the results from the model, we found the triad did have the characteristics of a master regulator.  The first time it's switched on, all the cells stay on. It also handles deactivation in a controlled manner, so that some cells differentiate and get deactivated and others don't. Finally, it has the ability to discern whether or not the level of signal is present only for a short burst or for a significantly long time."

Rice researchers hope that the regulatory triad motif reappears in other types of stem cells, possibly leading to more breakthroughs.

The results of the study are published in the journal 
PLoS Computational Biology.



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Stem Cells are not the answer to immortality
By sleepeeg3 on 5/7/2010 8:11:42 PM , Rating: 2
Despite the author's claims, stem cell research will never allow us to live indefinitely. Stem cells age, just like normal cells so even if we discover the ability to direct them into crafting entirely new organs, the organs they replace will be the same age as the rest of your body. This has to do with the shortening of telomeres and the loss of cells ability to protect their DNA, leading to mutations like cancer. Essentially, you could keep growing new organs to transplant back into your body, but if you use your own cells, they will only last approximately as long as the rest of you. This is why the cloned Dolly the sheep aged so quickly.
Here is a brief article on it: http://www.nature.com/nchembio/journal/v3/n10/abs/...

To compare this to a car, it is like turning your brake rotors. Rotors have the top layer scraped off to leave a fresh layer for your brake pads to grab, but eventually, they get too thin to be effective. Replacing them with new parts is the only real fix.

Now if we were to use fetal stem cells, we could generate organs with virtually no accumulated genetic damage, however donors would have to use anti-rejection drugs for the rest of their lives and with 1-100 trillion cells in the human body, this would only save the vital organs - not make us live forever.

If you want the answer to immortality, we have to solve the telomere problem. We have to find a way to activate the telomerase enzyme in our cells to regenerate our cell's protective telomeres, without allowing our cells to run amuck and become cancerous. Once we figure out how to control this, we also have the cure for cancer.

After we solve this, we can look at the other possible causes of genetic damage like oxidation of our mRNA that may be the other reasons for aging.




By dark matter on 5/8/2010 8:34:48 AM , Rating: 2
I don't we will ever be able to prevent ageing. It is such an important part of life that I believe you would have to fundamentally change so much DNA that we would no longer be even human.


By icanhascpu on 5/10/2010 5:44:20 PM , Rating: 2
Aging literally is preventable, its just way out of the reach of humanity right now and for many hundreds of years I would venture to guess. No to mention impractically expensive when we were do discover how to fix the degradation that happens to DNA.

I believe simple slowing of that degradation is going to be the future. We already live on average twice as long as we did a thousand years ago, and that is mainly from medical advances. The huge bottleneck a in human longevity is that degradation. Once that becomes slowed, or even able to regenerate that, mankind will see a huge jump in lifespan.

Saying its a part of life doesn't really mean anything. My computer crashing sometimes is a part of Windows too, but that doesn't stop MS from trying to improve the stability.

Saying they may not even be human from that is silly. Can they still breed with another human? Then they are human. Less syfy channel bro.


RE: Stem Cells are not the answer to immortality
By icanhascpu on 5/10/2010 5:32:47 PM , Rating: 2
So why not at birth or at some young age where such a procedure is most effective we have our own stem cells harvested to a degree, and frozen for use in the future.

That isn't immortality, and really, no one practical thinks that, but that solves a couple issues you're bringing up.


By icanhascpu on 5/10/2010 5:55:04 PM , Rating: 2
By sleepeeg3 on 5/14/2010 4:49:26 PM , Rating: 2
Storing stem cells at birth might eventually be a possibility, assuming they could be viable 60 years later. It could certainly help us live longer. The problem still remains that the rest of us is still aging (i.e. your skin) and will be more likely to become cancerous.

Genetic engineering at the fertilized egg cell stage will likely be the only way to permanently extend our lives. Finding a drug to turn on telomerase in our cells to continually rebuild our telomeres may be possible, but it is not going to solve the issues that seem likely to crop up with an increased risk of cancer. We also have to solve the problem with mitochondrial DNA damage due to oxidative stress. Can this all be solved with drugs? Maybe. I think the solution is obtainable within 50 years if we make a concerted effort to determine how to overcome these issues. Unfortunately, there are far too few researchers investigating this. I intend to become one of them.

Here is a fairly interesting overview on the subject:
http://nar.oxfordjournals.org/cgi/content/full/35/...

Would changing our DNA still make us human? Of course. Triggering something naturally in our DNA could just as easily have happened through a random mutation. If you want to look at the religious angle, we are using the minds that we were given to overcome inherent problems with our bodies. Do people see it as wrong to use medicine, glasses, sunscreen to overcome these defects or extend our lives? Of course not. This is just another physical limitation to be overcome by mankind.


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