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biggerbob

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Reply with quote  #1 
Starting the database out on the advances in stem cell research. Interesting article on how stem cells get coded to form different tissues. I wouldn't think it would be that hard to advance this to PE.

The Next Step Toward New Therapies - Predicting The Fate Of Personalized Cells

20 May 2011   

Discovering the step-by-step details of the path embryonic cells take to develop into their final tissue type is the clinical goal of many stem cell biologists. To that end, Kenneth S. Zaret, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, and associate director of the Penn Institute for Regenerative Medicine, and Cheng-Ran Xu, PhD, a postdoctoral researcher in the Zaret laboratory, looked at immature cells called progenitors and found a way to potentially predict their fate. They base this on how the protein spools around which DNA winds - called histones - are marked by other proteins. This study appeared this week in Science.

In the past, researchers grew progenitor cells and waited to see what they differentiated into. Now, they aim to use this marker system, outside of a cell's DNA and genes, to predict the eventual fate. This extra-DNA system of gene expression control is called epigenetics.

"We were surprised that there's a difference in the epigenetic marks in the process for liver versus pancreas before the cell-fate 'decision' is made." says Zaret. "This suggests that we could manipulate the marks to influence fate or look at marks to better guess the fate of cells early in the differentiation process."

"How cells become committed to particular fates is a fundamental question in developmental biology," said Susan Haynes, PhD, program director in the Division of Genetics and Developmental Biology at the National Institutes of Health, which funds this line of research. "This work provides important new insights into the early steps of this process and suggests new approaches for controlling stem-cell fate in regenerative medicine therapies."

A Guiding Path

How the developing embryo starts to apportion different functions to different cell types is a key question for developmental biology and regenerative medicine. Guidance along the correct path is provided by regulatory proteins that attach to chromosomes, marking part of the genome to be turned on or off. But first the two meters of tightly coiled DNA inside the nucleus of every cell must be loosened a bit. Regulatory proteins help with this, exposing a small domain near the target gene.

Chemical signals from neighboring cells in the embryo tell early progenitor cells to activate genes encoding proteins. These, in turn, guide the cells to become liver or pancreas cells, in the case of Zaret's work. Over several years, his lab has unveiled a network of the common signals in the mouse embryo that govern development of these specific cell types.

Zaret likens the complexity of this system to the 26-letter alphabet being able to encode Shakespeare or a menu at a restaurant. Many investigators are now trying to broadly reprogram cells into desired cell fates for potential therapeutic uses.

The researchers had previously shown that a particular growth factor that attaches to the cell surface, gives a specific chemical signal for cell-type fate, promoting development along the liver-cell path and suppressing development along the pancreas-cell path. Liver and pancreas cells originate from a common progenitor cell type.

Zaret's group figured out which enzymes - called histone acetyl transferases or methyl transferases (that add methyl groups or acetyl groups to histones) are relevant to the pancreas arm of the liver-pancreas fate decision. They used mice in which they knocked out the function for one enzyme type versus the other to induce the development of fewer liver cells and more pancreas cells.

The transferases mark genes for liver and pancreas fates differently before a cell moves into the next intermediate type along the way to becoming a mature liver or pancreas cell.

Investigators want to make embryonic stem cells for liver or pancreatic beta cells for therapies and research. To do this, they mimic the embryonic developmental steps to proceed from an embryonic stem cell to a mature cell, but have no way of knowing if they are on the right track. The hope is that the findings from this study can be applied to assess the epigenetic state of intermediate progenitor cells.

"By better understanding how a cell is normally programmed we will eventually be able to properly reprogram other cells," notes Zaret. In the near term, the team also aims to generate liver and pancreas cells for research and to screen drugs that repair defects or facilitate cell growth.

With regenerated cells, researchers hope to one day fill the acute shortage in pancreatic and liver tissue available for transplantation in cases of type I diabetes and acute liver failure.

The research was funded by the Institute of General Medical Sciences and the Institutes for Diabetes, Digestive, and Kidney Disorders.

Source:
Karen Kreeger
University of Pennsylvania School of Medicine
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skatezy777

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Reply with quote  #2 
For what it's worth: http://www.theatlanticwire.com/global/2011/07/first-fully-lab-grown-organ-successfully-transplanted/39733/
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biggerbob

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They seem to be getting closer to our holy grail of PE.
 
Using Patient’s Cells To Make Stem Cells To Replace Tissue
Monday, July 18, 2011 - Stem Cell Research News

VermaInder.png
Inder Verma

Scientists have developed an improved technique for generating large numbers of blood cells from a patient’s own cells.

The new technique will be immediately useful in further stem cell studies, and when perfected, could be used in stem cell therapies for a wide variety of conditions including cancers and immune ailments.

“There are further improvements that we need to make, but this takes us a significant step closer to the ultimate goal, which is to be able to take ordinary cells from a patient, induce them to become stem cells, and then use those stem cells to rebuild lost or diseased tissues, for example the patient’s bone marrow,” said Inder M. Verma, Ph.D., of the Salk Institute Laboratory of Genetics and senior author of the report.

Stem cell researchers have been racing towards this goal since 2006, when techniques for turning ordinary skin cells into induced pluripotential stem cells (iPSCs) were first reported. In principle, iPSCs mimic the embryonic stem cells (ESCs) from which organisms develop. Researchers now want to find the precise mixes and sequences of chemical compounds needed to coax iPSCs to mature into the tissue-specific stem cells of their choice. The latter are self-renewing, and can be transplanted into the body to produce the ‘progenitor’ cells that multiply locally and produce mature tissue cells.

However, researchers don’t know yet how to induce iPSCs to become tissue-specific stem cells or mature tissue cells with high efficiency. “We’ve been producing these cells in quantities that are too low to enable them to be studied easily, much less used for therapies,” said Aaron Parker, PhD, a former graduate student and now a postdoctoral researcher in Verma’s lab.

Like many other stem cell research laboratories, the Verma lab has been trying to find more efficient ways to turn iPSCs into blood-forming ‘hematopoietic’ stem cells (HSCs). These may be more valuable medically than any other tissue-specific stem cell, because they can supply not only oxygen-carrying red blood cells but also all the white blood cells of the immune system. “There would be an almost unlimited number of usages for true HSCs,” said Verma.

For the present study, the research team sought to do a better job of mimicking the changing conditions that naturally direct ESCs to become HSCs in the womb.

“We took seven lines of human ESCs and iPSCs, and experimented with different combinations and sequences of growth factors and other chemical compounds that are known to be present as ESCs move to the HSC state in a developing human,” said Parker.

Applying cocktails of these factors, Parker and Woods and their colleagues induced the iPSCs and ESCs to form colonies of cells that bore the distinctive molecular markers of blood cells. With their best such cocktail they were able to detect blood-specific markers on 84 percent of their cells after three weeks.

“That’s a big jump in efficiency from what we saw in the field just a few years ago,” said Parker.

The technique still has room for improvement. The researchers detected progenitor cells and mature cells from only one category or lineage: myeloid cells, which include red blood cells and primitive immune cells such as macrophages. “We didn’t see any cells from the lymphoid lineage, meaning T-cells and B-cells,” Parker said.

Another drawback was that the blood cell population they produced from ESCs and iPSCs contained short-lived progenitors and mature blood cells but no indefinitely renewing, transplantable HSCs. Their cocktail, they believed, either pushed the cells past the HSC state to the progenitor state too quickly, or made the maturing cells skip the HSC state entirely.

From this and other labs’ results, the team hypothesized the existence of an intermediate, pre-hematopoietic type of stem cell, produced by ESCs and iPSCs and in turn producing HSCs.

“We know that HSCs appear in a particular region of mammals during embryonic development, and our idea is that these pre-hematopoietic stem cells are there and are somehow made to mature into HSCs,” said Parker. “So our lab is now going to focus on finding the precise maturation signals provided by that embryonic region to produce these true, transplantable HSCs.”

Once that is done, researchers will need to make a number of further refinements to improve the safety of HSCs intended for human patients.

“But we’re now tantalizingly close to our ultimate goal,” said Verma.

The study was published in the July edition of the journal Stem Cells.

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HunkChunk

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Reply with quote  #4 
I guess we're not that far from being able to shop for a genetically engineered trade-in unit? lol

HC
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carlos_labrada

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Reply with quote  #5 
A little more on this subject, I believe that the use of extracellular matrix (ECM) are increasingly successful in regenerative medicine, the path to the aesthetic use is inevitable, we are seeing advances in the use of stem cells, ECM is more an encouragement for the future, I hope that is fast, LOL 
Link:

Stem Cells Regenerate New Finger!


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