Stem Cell Research Pushes the Envelope

Xavier434

Lifer
Oct 14, 2002
10,373
1
0
Ok, the topic summary is obviously exaggerated but this is just so awesome I couldn't help myself.

Source

Welcome to the stem cell revolution

There has been an ongoing morale debate in the U.S. which has crippled the funding of stem cells and left the future of stem cell research uncertain. Fortunately, about a year ago, scientists made an exciting breakthrough -- ordinary adult cells in mammals could be reprogrammed with viruses to become pseudo-stem cells. By eliminating the moral debate, the research reopened the door to one day developing treatments for Parkinson's Disease, Sickle Cell anemia, paralysis, and many other debilitating afflictions.


However, the pseudo-stem cells created from mice skin cells, known as induced pluripotent stem (IPS) stem cells, were not genetically identical like fetal stem cells, and required different methods of triggering for every tissue. Now scientists with Rudolph Jaenisch's lab at the Whitehead Institute for Biomedical Research have discovered a way to transform any type of tissue into a stem cell and ensure all the produced stem cells are genetically identical.

The transformation is triggered by the simple release of a drug; no additional genetic manipulation is necessary. Marius Wernig, one of the paper's two lead authors and a postdoctoral researcher at the lab stated, "This technical advancement will allow thousands of identical reprogrammed cells to be used in experiments."

"Using these cells could help define the milestones of how cells are reprogrammed and screen for drug-like molecules that replace the potentially cancer-causing viruses used for reprogramming," added Christopher Lengner, the other lead author and also a postdoctoral researcher at the lab.

Lengner alluded to an important fear with the current method. Past efforts used viruses to induce the transformation and it was found that the viruses could trigger cancer. A batch of stem cells could unwittingly contain cancer cells that could do far greater damage to the diseased person's body than the ailment they're being treated for.

While the new research still uses viruses, it is different in two important ways. First the viruses target a specific spot in the genome. Past efforts inserted genes anywhere in the genome, raising the likelihood of cancerous mutation. In the new research, lentiviruses artificial viruses, are used to randomly insert four genes (Oct4, Sox2, c-Myc and Klf4). All mice cells processed thusly have the same number of viral integrations in the same location within the genome. This both leads to genetically identical stems cells and cuts the cancer risk.

The second important way the research is different is that in its specificity, researchers can now focus on developing replacement molecules to the viruses, eliminating the cancer threat. The old research only worked on skin cells, so the focus was on developing different methods that could trigger various tissues to become IPS cells. The new method can trigger virtually any cell -- including cells from the intestine, brain, muscle, kidney, adrenal gland, and bone marrow -- into becoming an IPS cell.

After the cell is transformed, the cell was further modified to wait to switch on these genes upon a doxycycline trigger. This allowed researchers to control when they wanted to transform the cells into stem cells, with a simple chemical. The new method is much more efficient, with yields up from one in a thousand cells to one in twenty.

Jaenisch, who is also a professor of biology at Massachusetts Institute of Technology said, "In experiments, the technique will eliminate many of the reprogramming process's unpredictable variables and simplify enormously the research on the reprogramming mechanism and the screening for virus replacements."

The research can be found here in the July 1, 2008, online issue of Nature Biotechnology.

Funding for the research was provided by the Human Frontiers Science Organization Program, the Ellison Medical Foundation, the Ruth L. Kirschstein National Research Service Award, and the National Institutes of Health.
 

sdifox

No Lifer
Sep 30, 2005
101,224
18,231
126
not interested in living forever, just being ailment free would be great. Just think of all the seniors with joint problems.
 

Gibsons

Lifer
Aug 14, 2001
12,530
35
91
A virus expressing c-myc sounds like a good way to get cancer. Guess I'll have to read the paper though.
 

Xavier434

Lifer
Oct 14, 2002
10,373
1
0
Originally posted by: Gibsons
A virus expressing c-myc sounds like a good way to get cancer. Guess I'll have to read the paper though.

That concern is covered in the article. Part of why this is so cool is that it sounds like they are moving beyond that threat if they are not already beyond it with this new advancement. Only time will tell.
 

Gibsons

Lifer
Aug 14, 2001
12,530
35
91
Originally posted by: Xavier434
Originally posted by: Gibsons
A virus expressing c-myc sounds like a good way to get cancer. Guess I'll have to read the paper though.

That concern is covered in the article. Part of why this is so cool is that it sounds like they are moving beyond that threat if they are not already beyond it with this new advancement. Only time will tell.

If you mean in the OP, no not at all.

If you mean in the article, I'm not quite convinced.

The dox induction looks very clean in the data they present, but that might not be the case in differentiated cells in vivo - they generated the data from cultured cells. Also, some of the the isolated cells showed at least some evidence of transformation (loss of adherence, loss of contact inhibition) and they didn't do any long term looks at carcinogenesis. They also aren't really controlling the site of insertion and there's potentially a lot of problems there.

On the other hand, they briefly mention that it's possible to do the reprogramming without myc - makes me wonder why they included though.
 

skace

Lifer
Jan 23, 2001
14,488
7
81
I'll live forever, pump me full of that shit. I don't mind being a 300 year old ghoul.
 

Xavier434

Lifer
Oct 14, 2002
10,373
1
0
Originally posted by: Gibsons
Originally posted by: Xavier434
Originally posted by: Gibsons
A virus expressing c-myc sounds like a good way to get cancer. Guess I'll have to read the paper though.

That concern is covered in the article. Part of why this is so cool is that it sounds like they are moving beyond that threat if they are not already beyond it with this new advancement. Only time will tell.

If you mean in the OP, no not at all.

If you mean in the article, I'm not quite convinced.

The dox induction looks very clean in the data they present, but that might not be the case in differentiated cells in vivo - they generated the data from cultured cells. Also, some of the the isolated cells showed at least some evidence of transformation (loss of adherence, loss of contact inhibition) and they didn't do any long term looks at carcinogenesis. They also aren't really controlling the site of insertion and there's potentially a lot of problems there.

On the other hand, they briefly mention that it's possible to do the reprogramming without myc - makes me wonder why they included though.

The point is that they are making some great progress and we should be happy about that. The progress we have made with this research in the past 5 years alone is outstanding especially considering how much political opposition they have had to deal with.

No one is announcing a miracle cure here and nor is anyone aware of all the necessary facts to draw educated conclusions about where they actually stand with the cancer thing and other risks.
 

PingSpike

Lifer
Feb 25, 2004
21,766
615
126
Originally posted by: skace
I'll live forever, pump me full of that shit. I don't mind being a 300 year old ghoul.

Here we are! Born to be Kings, we're the Princes of the Un-i-verse!

I am immortal! I have inside me blood of kings...yeah! I have no rival, no man can be my equal!
 
Aug 23, 2000
15,509
1
81
Originally posted by: PingSpike
Originally posted by: skace
I'll live forever, pump me full of that shit. I don't mind being a 300 year old ghoul.

Here we are! Born to be Kings, we're the Princes of the Un-i-verse!

I am immortal! I have inside me blood of kings...yeah! I have no rival, no man can be my equal!

There can be only one!!!!

<chops off PingSpikes brown bag head>