Sunday, August 10, 2008

Stem cell news deluge

There's been a flood of news in the stem cell area during the past two weeks. A lot of it is important, and most of it builds on several themes related to stem cells that we've discussed before. In this post I'll just summarize the results and reference a press release. Watch for more details to follow.

Making new neurons from induced pluripotent stem cells

This is the only story here that's been reported more than a week ago (and just barely). Skin cells from an ALS (amyotrophic lateral sclerosis) patient have been reprogrammed into induced pluripotent stem cells, and then pushed towards development into motor neuron cells – containing the same defect that is manifested in ALS. These cells cannot be used to treat the disease. Instead, they will enable much more detailed research into the disease pathology.

Our most recent discussion of induced pluripotent stem cells is here.

First Neurons Created From ALS Patient's Skin Cells (7/31/08)
Harvard and Columbia scientists have for the first time used a new technique to transform an ALS ... patient's skin cells into motor neurons, a process that may be used in the future to create tailor-made cells to treat the debilitating disease.

The research – led by Kevin Eggan, Ph.D. of the Harvard Stem Cell Institute – will be published July 31 in the online version of the journal Science.

This is the first time that skin cells from a chronically-ill patient have been reprogrammed into a stem cell-like state, and then coaxed into the specific cell types that would be needed to understand and treat the disease.


Cell lines for genetic disease research

Just like the work described above, cell lines from 9 additional genetic disease have been derived from induced pluripotent stem cells, which were in turn derived from fully differentiated cells, skin cells in most cases. These cell lines will also be used for research into disease pathology. Most of the diseases in question are considered to result from mutations in more than a single gene, so that understanding the disease necessitates research into how several defective genes interact with each other or with environmental influences.

The better-known of the diseases involved are muscular dystrophy, Parkinson's disease, Huntington's disease, type 1 diabetes, and Down syndrome. There's quite a bit of news hype surrounding this announcement – although it's extremently important from a research standpoint – because the cells cannot be used as a treatment, since they carry the disease's genetic defect.

Twenty Disease-specific Stem Cell Lines Created (8/7/08)
A set of new stem cell lines will make it possible for researchers to explore ten different genetic disorders—including muscular dystrophy, juvenile diabetes, and Parkinson's disease—in a variety of cell and tissue types as they develop in laboratory cultures.

Harvard Stem Cell Institute researcher George Q. Daley, MD, PhD, also associate director of the Stem Cell Program at Children's Hospital Boston, and HSCI colleagues Konrad Hochedlinger and Chad Cowan have produced a robust new collection of disease-specific stem cell lines, all of which were developed using the new induced pluripotent stem cell (iPS) technique.


Improved technique for making induced pluripotent stem cells

You may recall from our discussion of induced pluripotent stem cells (here) that the resulting cells are vulnerable to becoming cancerous (as has been confirmed in experiments on mice), because they depend on overexpression of the gene for the c-Myc transcription factor. The new research shows that it is possible to obtain induced pluripotent stem cells by overexpressing a member of the important Wnt family of signaling proteins. (We've covered Wnt several times, most recentely here.)

Embryonic-like Stem Cells Can Be Created Without Cancer-causing Gene (8/6/08)
A drug-like molecule called Wnt can be substituted for the cancer gene c-Myc, one of four genes added to adult cells to reprogram them to an embryonic-stem-cell-like state, according to Whitehead researchers.

Researchers hope that such embryonic stem-cell-like cells, known as induced pluripotent (IPS) cells, eventually may treat diseases such as Parkinson's disease and diabetes.


Controling embryonic stem cell development

For all the future potential that may come from research into induced pluripotent stem cells, they are sufficiently different from true embryonic stem cells that we can't fully understand the latter by studing the former. In particular, true embryonic stem cells may be easier to push into any differentiated cell type, without the same cancer risk. New research illuminates development of endoderm cells from embryonic stem cells. Specific types of endoderm cells include cells of the lungs and pancreas (among many others).

Our most recent discussion of embryonic stem cells is here.

Scientists uncover the key to controlling how stem cells develop (8/8/08)
The results of a new study involving a McMaster University researcher provide insight into how scientists might control human embryonic stem cell differentiation.

In collaboration with researchers from SickKids and Mount Sinai hospitals, Dr. Jon Draper, a scientist in the McMaster Stem Cell and Cancer Research Institute, focused on producing early endoderm cells from human embryonic stem cells. ...

The researchers focused on generating stable progenitor cells capable of producing all endoderm cell types. The cells were able to maintain their distinct profiles through many stages of cell culture without losing their ability to self renew.


MicroRNA and embryonic stem cells

The last time we discussed microRNA in connection with embryonic stem cells (here) we saw that microRNA controlled genes that enabled the cells' self-renewal and differentiation properties. The latest research takes a much closer look at how microRNA and conventional transcription factors work together to regulate differentiation of embryonic stem cells, and also how they play a role in making induced pluripotent stem cells from differentiated cells.

Putting MicroRNAs On The Stem Cell Map (8/7/08)
Embryonic stem cells are always facing a choice—either to self-renew or begin morphing into another type of cell altogether.

It's a tricky choice, governed by complex gene regulatory circuitry driven by a handful of key regulators known as "master transcription factors," proteins that switch gene expression on or off.

In the past few years, scientists in the lab of Whitehead Member Richard Young and their colleagues have mapped out key parts of this regulatory circuitry, but the genes that produce the tiny snippets of RNA known as microRNAs have until now been a missing piece of the map. Since microRNAs are a second set of regulators that help to instruct stem cells whether to stay in that state, they play key roles in development.

Young and colleagues have now discovered how microRNAs fit into the map of embryonic stem cell circuitry. With this map, the scientists have moved one step closer to understanding how adult cells can be reprogrammed to an embryonic state and then to other types of cells, and to understanding the role of microRNAs in cancer and other diseases.


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2 Comments:

Blogger wheelst said...

funny how the medical profession is so far behind the Veterinarians, There is a Vet in Carmel who takes stems cells from a dogs fat and re- injects them in the dogs hips to fix denigrative bone disease.

8/14/2008 08:42:00 PM  
Blogger Charles Daney said...

funny how the medical profession is so far behind the Veterinarians

I don't know about this specific situation, but the main reason development of therapeutics for human use takes so long and is so expensive is that very thorough testing has to be done for both safety and efficacy. (And obviously, even then, not all safety problems get caught.)

You have to ask yourself whether you would choose to have such a procedure for yourself if there were a risk of (say) cancer. And what if it was expensive - wouldn't you want to know how likely it would successfully cure the problem?

I don't know what sort of standards, if any, apply for animal therapies. But again, how much risk would you want to take with your own dog, and how much would you want to pay if there hadn't been much testing of whether the proposed therapy was safe and effective?

You'd probably accept more risk with your dog than with your child - and it just takes a lot of time to do enough studies to achieve reasonable certainty about the risks for humans.

8/15/2008 12:44:00 AM  

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