Stem Cell Research

Virus-Free Technique Enables Researchers To Easily Make Fat Stem Cells Pluriotent

Stem cells from human fat are multipotent to begin with, meaning they are basically designed to turn into fat, bone or muscle tissue. While skin cells have been extensively used to create induced pluripotent (iPS) cells in the two plus years since iPS cells were first demonstrated, the ready multipotency and available supply of fat stem cells were seen by Stanford researchers as perhaps an easier approach.

Tiny circles of DNA turned out to ve the key to a new and easier way to transform stem cells from human fat into induced pluripotent stem (iPS) cells.  Unlike other commonly used techniques, the method, which is based on standard molecular biology practices, does not use viruses to introduce genes into the cells or permanently alter a cell's genome.

The new technique is the first example of reprogramming adult cells to pluripotency in this manner, and is hailed by the researchers as a major step toward the use of such cells in humans. They hope that the ease of the technique and its relative safety will smooth its way through the necessary FDA approval process.

"This technique is not only safer, it's relatively simple," said Stanford surgery professor Michael Longaker, MD, and co-author of the paper. "It will be a relatively straightforward process for labs around the world to begin using this technique. We are moving toward clinically applicable regenerative medicine."

The Stanford researchers used the so-called minicircles - rings of DNA about one-half the size of those usually used to reprogram cells - to induce pluripotency in stem cells from human fat. Pluripotent cells can then be induced to become many different specialized cell types. Although the researchers plan to first use these cells to better understand - and perhaps one day treat - human heart disease, induced pluripotent stem cells, or iPS cells, are a starting point for research on many human diseases.

"Imagine doing a fat or skin biopsy from a member of a family with heart problems, reprogramming the cells to pluripotency and then making cardiac cells to study in a laboratory dish," said cardiologist Joseph Wu, MD, PhD. "This would be much easier and less invasive than taking cell samples from a patient's heart." Wu is the senior author of the research.  Research assistant Fangjun Jia, PhD is the lead author of the work.
      
The minicircle reprogramming vector works so well because it is made of only the four genes needed to reprogram the cells (plus a gene for a green fluorescent protein to track minicircle-containing cells). Unlike the larger, more commonly used DNA circles called plasmids, the minicircles contain no bacterial DNA, meaning that the cells containing the minicircles are less likely than plasmids to be perceived as foreign by the body. The expression of minicircle genes is also more robust, and the smaller size of the minicircles allows them to enter the cells more easily than the larger plasmids. Finally, because they don't replicate they are naturally lost as the cells divide, rather than hanging around to potentially muck up any subsequent therapeutic applications.
      
The researchers chose to test the reprogramming efficiency of the minicircles in stem cells from human fat because previous work in Wu and Longaker's lab has shown that the cells are numerous, easy to isolate and amenable to the iPS transformation, probably because of the naturally higher levels of expression of some reprogramming genes. They found that about 10.8 percent of the stem cells took up the minicircles and expressed the green fluorescent protein, or GFP, versus about 2.7 percent of cells treated with a more traditional DNA plasmid.
      
When the researchers isolated the GFP-expressing cells and grew them in a laboratory dish, they found that the minicircles were gradually lost over a period of four weeks. To be sure the cells got a good dose of the genes, they reapplied the minicircles at days four and six. After 14 to 16 days, they began to observe clusters of cells resembling embryonic stem cell colonies - some of which no longer expressed GFP.
      
They isolated these GFP-free clusters and found that they exhibited all of the hallmarks of induced pluripotent cells: they expressed embryonic stem cell genes, they had similar patterns of DNA methylation, they could become multiple types of cells and they could form tumors called teratomas when injected under the skin of laboratory mice. They also confirmed that the minicircles had truly been lost and had not integrated into the stem cells' DNA.
      
Altogether, the researchers were able to make 22 new iPS cell lines from adult human adipose stem cells and adult human fibroblasts. Although the overall reprogramming efficiency of the minicircle method is lower than that of methods using viral vectors to introduce the genes (about 0.005 percent vs. about 0.01-0.05 percent, respectively), it still surpasses that of using conventional bacterial-based plasmids. Furthermore, stem cells from fat, and, for that matter, fat itself, are so prevalent that a slight reduction in efficiency should be easily overcome.

Adapted from the Stanford University School of Medicine announcement.

Researchers Transform Mouse Skin Cells Into Neurons, Skipping Induced Pluripotent Stem Cell Stage

The future of regenerative medicine continues to depend on the type of stem cell that is proven most effective, most scalable, and most time and cost efficient to produce.  Approaches include embryonic stem cells, adult stem cells, Induced pluripotent stem cells, from both autologous and allogeneic sources.  One of our Sector Companies, International Stem Cell Corp., is attempting to create a stem cell bank based on parthenogenic stem cells derived from unfertilized eggs (oocytes).  Such a bank would have the following advantages:

1. A scalable bank would contain a manageable number of stem cell lines that will be immunological matches for large patient populations of different ethnic origin.


2. Unlike induced pluripotent stem (iPS) cells these would not involve extensive gene manipulation, which to this point in time have largely unknown biological impact.

We point this out in order to ask ourselves what the potential impact on such a stem cell bank might be from new study results obtained by researchers at Stanford University.  Since human iPS cells were first created in late 2007, the emphasis has been on developing these cells in a faster, cheaper way that also provides safe and predictable biological results when used in regenerative therapies.

But what if the iPS phase can be skipped entirely?  Will adult cells converted, for example, directly  into nerve cells be an eventual solution to Parkinson's Disease?  Or will parthenogenic, or some other more basic, more embryonic-like, cell provide the answer.  Perhaps both will be a solution and success in the market, as well as in therapy, will be a function of efficiency from origin to therapeutic use, and resultant lower cost. Perhaps neither will be universally useful in general therapy, but will be more effective for therapies in particular parts of the body.  At this stage no one knows for sure.  What we do know is that knowledge is expanding rapidly as shown in this current Stanford study.

Stanford researchers have succeeded in transforming mouse skin cells in a laboratory dish directly into functional nerve cells with the application of just three genes. The cells make this transition without first becoming a pluripotent type of stem cell.

Researchers Generate Abundant Functional Blood Vessel Cells From Embryonic And Induced Pluripotent Stem Cells

Researchers have developed a new technique -- and described a novel mechanism -- for turning human embryonic and pluripotent stem cells into plentiful, functional endothelial cells, which are critical to the formation of blood vessels. Endothelial cells form the interior "lining" of all blood vessels and are the main component of capillaries, the smallest and most abundant vessels.

The new approach allows scientists to generate virtually unlimited quantities of durable endothelial cells -- more than 40-fold the quantity possible with previous approaches.

"This technique is the first of its kind with serious potential as a treatment for a diverse array of diseases, especially cardiovascular disease, stroke and vascular complications of diabetes," said Dr. Shahin Rafii, the study's senior author and Arthur B. Belfer Professor in Genetic Medicine and co-director of the Ansary Stem Cell Institute at Weill Cornell Medical College. Dr. Rafii is also an investigator of the Howard Hughes Medical Institute.

Researchers first screened for molecular factors that come into play when stem cells turn into endothelial cells. Their findings led them to a strategy that significantly boosts the efficiency of producing these cells.

They then tracked the differentiation process in real-time using a green fluorescent protein marker developed by Dr. Daylon James, the study's first author and assistant research professor in the Department of Reproductive of Medicine at Weill Cornell Medical College. They found that when they exposed stem cells to a compound that blocks TGF-beta (a growth factor involved in cell specialization) at just the right time during cell culturing, the propagation of endothelial cells dramatically increased.

Molecule Identified That Inhibits Stem Cell Differentiation

It turns out that stem cells have need for long-term memory to help them know who they are and what they should become. Researchers at the Stanford University School of Medicine have now identified a molecule involved in keeping skin stem cells on the straight and narrow path.

“We’re starting to understand the molecular mechanism of cellular memory,” said Paul Khavari, MD, PhD, professor of dermatology. “How a stem cell remembers what it is, and why it might go astray.”

The molecule, called DNMT1, helps the stem cells know whether to self-renew to create more stem cells, or to differentiate into specialized, non-dividing adult skin cells. It’s important because too much self-renewal can lead to cancer, and too little can inhibit wound healing.

Much ado is made over pluripotent cells — such as embryonic stem cells and their laboratory doppelgangers, induced pluripotent stem (iPS) cells — which have the potential to differentiate into any of the body’s different cell types. But adult stem cells, while more limited in their ability to create new types of cells, still have important roles in the body. They’re particularly vital in skin, blood and other tissues that must constantly regenerate new cells.

Ethnic Origin Of Stem Cells Found Important To Safety And Effectiveness Of Specific Future Drugs

Analysis of a variety of human embryonic stem cell lines determined that the cells originated largely from Caucasian and East Asian populations, with little representation from populations originating in Africa.  The lines analyzed are currently in use in research laboratories around the world.  In response to these results, scientists from Scripps Research Institute used skin cells from an individual of West African Yoruba heritage to create a new stem cell line, the first to carry the genetic profile of this ethnic group.

Why is this important? Research has shown that discordance between the ethnic origin of organ donors and recipients can influence medical outcomes for tissue transplantation, and that the safety and effectiveness of specific drugs can vary widely depending on ethnic background.

"Ethnic origin is a critical piece of information that should come with every cell line," said Scripps Research Professor Jeanne Loring, who is senior author of the paper resulting from this research. "Everyone who works with stem cells should be doing this kind of analysis."

One of our Sector Companies, International Stem Cell Corp. (ISCO) announced a collaboration with Dr. Jeanne Loring and Scripps Research in November of last year.  ISCO has developed a parthenogenetic homozygous stem cell line and is hopeful that this research will provide immune-matched stem cells for human transplant which will allow the building of a "stem cell bank" that could offer on-demand delivery of stem cells matched to a patient’s own immune system.

"Knowing that a big push in the future is using stem cell lines in the clinic and in drug development, there's a need to have an ethnically diverse population of cells," added Louise Laurent, assistant professor at the University of California, San Diego (UCSD) and research associate at Scripps Research, who is first author of the paper with Caroline Nievergelt, also an assistant professor at UCSD.

China's Star Rising Despite World Skepticism Of Its Past Stem Cell Research Approaches

Despite world skepticism of China's research approach to stem cell therapies, Medical Tourism continues to grow as China's government pours generous dollars into research on regenerative medicine and aggressively recruits high-caliber scientists trained abroad in pursuit of its ambition to become a world leader in the field.  This According to a study by the Canadian-based McLaughlin-Rotman Centre for Global Health (MRC).  As a result of its expanded investment, Chinese contributions to scientific journals on RM topics leapt from 37 in year 2000 to 1,116 in 2008, exceeded only by the contributions of experts in the USA, Germany, Japan and the UK.

The accomplishment is all the more interesting given that China's international credibility has been and still is severely hindered by global concerns surrounding Chinese clinics, where unproven therapies continue to be administered to thousands of patients, including an increasing number of desperate Westerners fueling Medical Tourism which has become a growth industry.

"When you look at the issue of stem cells in China, you see the Yin-Yang of a scientific powerhouse mixed with controversial clinical application of stem cell therapies," said Dr. Peter Singer, MRC's Director. "The overall picture at the moment is ambiguous but in the future, given the measures that have been put in place, the science can be expected to rise and the controversy to fall."

Until May 2009, clinical trials to determine the effectiveness of stem cell therapies were not required in China. Now proof of safety and efficacy through clinical trials is required by China's Ministry of Health for all stem cell and gene therapies.

The change was made after international experts, joined by top Chinese researchers, protested that treatment centers were acting "against commonly accepted principles of modern scientific research" and successfully called on China to regulate new treatments and ensure patient safety.

Despite the new rules, however, stem cell treatments are still available at over 200 hospitals across China to patients of diseases such as ataxia, Lou Gehrig's disease, traumatic brain and spinal cord injury, diabetes, Parkinson's, multiple sclerosis, autism, cerebral palsy, stroke, optic nerve hypoplasia and many others.

"To our knowledge, Chinese policy makers and ethicists are working out the regulation details,” says Ms. McMahon, the study's lead author. "Once that is accomplished, we still expect a delay, during which the therapies currently administered by clinics and hospitals will be evaluated individually to determine whether they meet the criteria of China's Ministry of Health."

Immune System Protein Found To Be Important In Reprogramming Adult Cells Into iPS Cells

Researchers at Stanford’s School of Medicine have discovered a protein required to quickly and efficiently reprogram human skin cells to express embryonic stem cell genes. The finding could eliminate a major bottleneck in the generation of iPS and embryonic stem cells — that of removing molecular tags called methyl groups from specific regions of cellular DNA. Without this process of demethylation, the stem cell genes are silent in adult, or differentiated, cells.

Since the first human skin cell was reprogrammed into an embryonic-like cell in 2007, scientists have believed there is much promise for induced pluripotent stem cells, considering them to have the potential to be used to repair damaged tissue and treat the ravages of disease.  The problem has been that making these so-called iPS cells is both time-consuming and inefficient.

“The mechanism of DNA demethylation in mammals has eluded us for decades,” said Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor and member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “Now we’ve identified a protein involved in targeted DNA demethylation, and we’ve also shown that it’s critically important in reprogramming adult cells to function more like their stem cell predecessors.” Blau is the senior author of the research.

The researchers used a high-efficiency cell fusion strategy to identify the protein, called activation-induced cytidine deaminase, or AID. This protein is most commonly known for its involvement in the immune system in generating germ-fighting antibodies. But Blau and her colleagues uncovered an unexpected presence — and an unanticipated role — of the protein in embryonic stem cells.

Researchers anticipate that harnessing the activity of AID and other proteins with which it may work could revolutionize the generation of iPS cells. It may also help in creating embryonic stem cells through a process called somatic cell nuclear transfer. Both methods rely on the removal of the molecular tags from specific regions of DNA.

Magnetism And Nanotubes May Be Means Of Directing Stem Cells To Specific Point Where Treatment Is Needed

In August, University College London researchers demonstrated a technique whereby endothelial progenitor cells – a type of stem cell shown to be important in vascular healing processes – were magnetically tagged with a tiny iron-containing clinical agent, then successfully targeted to a site of arterial injury using a magnet positioned outside the body.

The result was a five-fold increase in cells at a site of vascular injury in rats. The team also demonstrated a six-fold increase in cell capture in an in vitro flow system (where microscopic particles are suspended in a stream of fluid and examined to see how they behave).

Dr Mark Lythgoe, UCL Centre for Advanced Biomedical Imaging and lead researcher said, "Because the material we used in this method is already FDA approved we could see this technology being applied in human clinical trials within 3-5 years. It’s feasible that heart attacks and other vascular injuries could eventually be treated using regular injections of magnetized stem cells. The technology could be adapted to localize cells in other organs and provide a useful tool for the systemic injection of all manner of cell therapies. And it’s not just limited to cells – by focusing tagged antibodies or viruses using this method, cancerous tumors could be much more specifically targeted.”

Panagiotis Kyrtatos, also from the UCL Centre for Advanced Biomedical Imaging and lead researcher of the study, added: “This research tackles one of the most critical challenges in the biomedical sciences today: ensuring the effective delivery and retention of cellular therapies to specific targets within the body."

Now, Rice University and the Texas Heart Institute have received a two-year $1 million Challenge Grant to develop an advanced stem-cell-tracking technology based on an ultrasensitive class of magnetic resonance imaging (MRI) contrast agents invented at Rice in 2005.

The grant's purpose is the refinement of cell-tracking nanotube technology that could make magnetic resonance imaging (MRI) up to 40 times more sensitive than existing MRIs and help guide adult stem cells within the human body to repair damaged hearts.

Unraveling The Mechanisms Behind Organ Regeneration

The search for the holy grail of regenerative medicine—the ability to "grow back" a perfect body part when one is lost to injury or disease—has been under way for years, yet the steps involved in this seemingly magic process are still poorly understood.

Some time ago we posted about Max Planck Institute research on Salamanders.  Salamanders regrow lost limbs and Elly Tanaka at Planck has been studying how they do so. Tanaka and colleagues found that salamander regeneration begins when a clump of cells called a blastema forms at the tip of a lost limb. From the blastema come skin, muscle, bone, blood vessels and neurons, ultimately growing into a limb virtually identical to the old one.

But here's the surprise: Rather than having their cellular clocks fully reset and reverting to an embryonic state, cells in the salamanders’ stumps became slightly less mature versions of the cells they’d been before.  In other words they don't revert to pluripotency.

Now researchers at the Salk Institute for Biological Studies have identified an essential cellular pathway in zebrafish that paves the way for limb regeneration by unlocking gene expression patterns last seen during embryonic development. They found that a process known as histone demethylation switches cells at the amputation site from an inactive to an active state, which turns on the genes required to build a copy of the lost limb.

Salk Institute researchers, lead by Juan Carlos Izpisúa Belmonte Ph.D, used zebrafish, a small fish from the minnow family, to study limb regeneration. "If you amputate the tail of the zebrafish, it regenerates in about a week, seemingly with no effort and leaving no scar," explains Scott Stewart Ph.D. "What's more, it regenerates a perfect copy and—like growing grass—it will do this over and over again." In other words, the zebrafish has the same regenerative capacity as the salamander.

Johns Hopkins and Harvard Add To Previous 2009 Findings On Differnces Between Induced Pluripotent And Embryonic Stem Cells

In July 2009, UCLA and Broad Institute researchers analyzed induced pluripotent stem cell lines derived with newer methods that didn't require integration of the reprogramming factors. Their analysis showed different molecular signatures between iPS cells and their embryo-derived counterparts, and these signatures showed a significant degree of overlap with those generated with integrative methods.

"We can’t explain this, but it appears something is different about iPS cells and embryonic stem cells,” said Bill Lowry, a researcher with the Broad Stem Cell Research Center. “The differences are there, no matter whose lab the cells come from, whether they’re human or mouse cells or the method used to derive the iPS cells. Perhaps most importantly, many of these differences are shared amongst lines made in various ways.”

Then in September came work regarding the differences between induced and embryonic stem cells done by UCSD and the Salk Institute. 

By creating iPSCs from human neural stem cells without the use of viruses, UCSD and Salk scientists learned something that moved toward an explaination of some of the questions raised by the UCLA/Broad Institute results. What they found was this: While the genetic transcriptional profile of the new iPSCs was closer to that of embryonic stem cells than to human neural stem cells, the iPSCs still carried a transcriptional "signature" of the original neural cell.

"While most of the original genetic memory was erased when the cells were reprogrammed, some was retained," said lead researcher Alysson R. Muotri, UCSD Stem Cell Program researcher who added that in the past it wasn't known if this retinue was caused by the use of viral vectors.

Although genetically identical to the mature body cells from which they are derived, induced pluripotent stem cells (iPSCs) are notably special in their ability to self-renew and differentiate into all kinds of cells. Now researchers from Johns Hopkins and Harvard have detected a remarkable if subtle molecular disparity between the two: Turns out they have distinct "epigenetic" signatures; that is, they differ in what gets copied when the cell divides, even though these differences aren't part of the DNA sequence.

Gladstone And Stanford To Develop Induced Pluripotent Stem (IPS) Cells For Cardiac Stem Cell Treatments

Researchers from the Gladstone Institute of Cardiovascular Disease (GICD), led by Director Deepak Srivastava, MD, will collaborate with a Stanford research team led by Robert Robbins, MD, professor and chair of cardiothoracic surgery, to investigate the use of induced pluripotent stem cells (iPS cells) to repair damaged heart muscle. The research consortium will be funded by the National Heart, Lung and Blood Institute (NHLBI).

iPS cells result from the “reprogramming” of adult cells into cells closely resembling embryonic stem cells. Like ESCs, they can develop into any cell type in the body. This technology was developed by Gladstone investigator Shinya Yamanaka, MD, PhD. the 2009 Lasker Award Recipient for Biomedical Research.

"Important gaps remain in our understanding of stem and progenitor cells," said NHLBI director Elizabeth Nabel, MD. "This consortium holds great promise to expand our knowledge and uncover therapeutic applications of great public impact.”

Small Molecule Platform For Commercial-Scale Reprogramming Announced

Fate Therapeutics, Inc. claims to have significantly improved the speed and efficiency of reprogramming adult cells into human induced-pluripotent stem cells (iPSCs) using a combination of small molecules.

The discovery, which was made by Sheng Ding, Ph.D. under a research collaboration between Fate Therapeutics and The Scripps Research Institute (TSRI), represents a more than 200-fold improvement in reprogramming efficiency and reduces the reprogramming period to two weeks as compared to methods using only the four reprogramming factors (Oct 3/4, Sox2, Klf4 and c-Myc).

This advancement has implications for the creation of "pharmaceutical grade" iPSCs, reprogrammed cells that can be produced without genetic modification at commercial scale quantity, quality and consistency.

Harvard Stem Cell Research Team Reports Major Step In Producing Induced Pluripotent Stem Cells

Finding a way to produce safe iPS cells that are the biological equivalent of embryonic stem cells is especially important because the cells can then be created from the cells of individual patients for transplantation into those patients. Once accomplished, a patient with Parkinson’s disease might be treated with neurons created from his own cells, theoretically eliminating the need for immunosuppressive drugs, or the possibility of rejection of the transplanted cells. Similarly, patient-specific iPS cells could be used to create muscle for damaged hearts, or other individualized treatments.

A team of Harvard Stem Cell Institute (HSCI) researchers has made a major advance toward producing induced pluripotent stem cells, or iPS cells, that are safe enough to use in treating diseases in patients.

“We’re halfway home, and remarkably we got halfway home with just one chemical,” said Kevin Eggan, a Harvard Stem Cell Institute principal faculty member who is the senior author of this study.

NHLBI Awards $170 Million To Create The Progenitor Cell Biology Consortium And Fund Related Stem Cell Research

The National Heart, Lung, and Blood Institute (NHLBI), one of the National Institutes of Health, has awarded $170 million to be paid over seven years to 18 teams of research scientists to develop the high-potential field of stem and progenitor cell tools and therapies.

The awards create the NHLBI Progenitor Cell Biology Consortium, which will bring together researchers from the heart, lung, blood, and technology research fields. A seven-year project, the consortium assembles nine research hubs with multidisciplinary teams of principal investigators and an administrative coordinating center to focus on progenitor cell biology.

“This is a grand experiment,” said Irving Weissman, MD, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “By forming this consortium, the NHLBI is encouraging a dialogue between scientific groups that would otherwise be competing with one another. I am very excited, and have high hopes that this will accelerate the understanding of stem and progenitor cells to the point of medical therapies.”

Umbilical Cord Blood Found To Be Ready Source For Off-The-Shelf, Patient-Specific, Induced Pluripotent Stem cells

Umbilical cord blood cells can successfully be reprogrammed to function like embryonic stem cells, thus setting the basis for a comprehensive bank of tissue-matched, cord blood-derived induced pluripotent stem (iPS) cells for off-the-shelf applications.

Worldwide, there are already more than 400,000 cord blood units banked along with immunological information. Cells found in umbilical cord blood contain a minimal number of cell mutations and possess the immunological immaturity of newborn cells, allowing the HLA donor-recipient match to be less than perfect without the risk of immune rejection of the transplant.

Human leukocyte antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants. HLAs are special surface markers found on most cells in the body and help the immune system to distinguish between "self" and "non-self." Selecting common HLA haplotypes from among already banked cord blood units to create iPS cell would significantly reduce the number of cell lines needed to provide a HLA match for a large percentage of the population.

Since the first adult cells were converted into iPS cells, they have generated a lot excitement as an uncontroversial alternative to embryonic stem cells and as a potential source for patient-specific stem cells. Unfortunately, taking a patient's cells back in time is not only costly, but could be difficult when those cells are needed right away to mend injured spinal cords or treat acute diseases, and outright impossible when the effects of aging or chronic disease have irrevocably damaged the pool of somatic cells.

Understanding The Differences Between Induced Pluripotent Stem Cells And Embryonic Stem Cells

In July we posted about genetic differences found between Induced Pluripotent Stem (iPS) cells and embryonic stem cells.  Researchers at UCLA and the Broad Stem Cell Institute had performed microarray gene expression profiles on embryonic stem cells and iPS cells to measure the expression of thousands of genes at once, creating a global picture of cellular function.

When the molecular signatures were compared, it was clear that certain genes were expressed differently in embryonic stem cells than they were in iPS cells. The researchers then compared their data to that stored on a National Institutes of Health data base, submitted by laboratories worldwide. They analyzed that data to see if the genetic profiling conducted in other labs validated their findings, and again they found overlapping but distinct differences in gene expression.

UCLA and Broad researchers then analyzed cell lines derived with newer methods that do not require integration of the reprogramming factors. Their analysis again showed different molecular signatures between iPS cells and their embryo-derived counterparts, and these signatures showed a significant degree of overlap with those generated with integrative methods.

"We can’t explain this, but it appears something is different about iPS cells and embryonic stem cells,” said Bill Lowry, a researcher with the Broad Stem Cell Research Center and a study author..“And the differences are there, no matter whose lab the cells come from, whether they’re human or mouse cells or the method used to derive the iPS cells. Perhaps most importantly, many of these differences are shared amongst lines made in various ways.”

In the latest step forward, San Diego School of Medicine and the Salk Institute for Biological Studies in La Jolla have developed a safe strategy for reprogramming cells to a pluripotent state without use of viral vectors or genomic insertions.

Liposuction Excess Easily Converted To IPS Cells, Stanford Study Shows

In a finding that independently adds support to the Cellution systems manufactured by Cytori Therapeutics, one of our Sector Companies, and the TGI 1200 System (supplied by privately held Tissue Genesis' to Sector Company BioHeart Inc.), Stanford researchers have found that human fat removed during liposuction conceals versatile cells that are more quickly and easily coaxed to become induced pluripotent stem cells, or iPS cells, than are the skin cells most often used by researchers.

"We've identified a great natural resource," said Stanford surgery professor and co-author of the research, Michael Longaker, MD, who has called the readily available liposuction leftovers "liquid gold." Reprogramming adult cells to function like embryonic stem cells is one way researchers hope to create patient-specific cell lines to regenerate tissue or to study specific diseases in the laboratory.

Wisconsin Research Team Creates Retinal Cells From Skin Cells

A few weeks ago we posted about University of Florida researchers chemically inducing bone marrow stem cells to become retinal cells. Now University of Wisconsin researchers have broadened the Florida result.

The University of Wisconsin retina project began by using embryonic (ES) stem cells, but incorporated induced pluripotent stem (iPS) cells as they became available. Ultimately, Wisconsin researchers were able to grow multiple types of retinal cells beginning with either ES or iPS cells, each of which provided a highly enriched population of very primitive cells with the potential to become retinal cells.

In normal human development, embryonic stem cells begin to differentiate into more specialized cell types about five days after fertilization. The retina develops from a group of cells that arise during the earliest stages of the developing nervous system. The Wisconsin team took cells from skin, created induced pluripotent stem cells, and then coaxed them into becoming retinal cell types.

Technique Enables Efficient Gene Targeting In Human Embryonic And Induced Pluripotent Stem Cells

Use of a novel technique has allowed researchers to efficiently and precisely modify or introduce genes into the genomes of human embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells.  The method uses proteins called zinc finger nucleases and may create methodology for determining how embryonic stem cells mature into adult stem cells, thereby improving research methods in each.

For years, scientists have easily swapped genes in and out of mouse ESC or iPS cell genomes, but have had a notoriously difficult time disrupting or inserting genes into their human equivalents.

“It’s not clear where this hurdle of genetic manipulation lies; it could be purely technical, but it could also be an inherent difference between human and mouse cells,” says Dirk Hockemeyer. Hockemeyer and Frank Soldner are first authors on the study and postdoctoral researchers in stem cell pioneer Rudolf Jaensich’s laboratory at the Whitehead Institute. “Other people have genetically manipulated these human cells, but the process has been extremely laborious and extremely time consuming. Using the zinc finger nucleases makes the process very easy,” says Hockemeyer.

Induced Pluripotent Stem Cell Research Advances Prompt Unique NIH Autism Research Grant

In a quiet but firm acknowledgement of adult stem cell transplant therapy and treatment potential from Induced Pluripotent Stem Cell research, the National Institute of Health has granted Children's Hospital of Orange County (CHOC) three million dollars over five years to collect skin cells from children with autism.  The skin cells will be induced into becoming neural cells which can then be studied to gain insight into the autism spectrum and hopefully to find corrective measures.

The NIH-funded research at CHOC will apply this new technology to fibroblasts derived from patients whose autism is clinically very well-characterized, as well as those derived from individuals without the disorder.  This efficient, non-invasive method for generating autism neural stem cells from living individuals will allow research that has never been possible before.

It will allow studies of the detailed properties of the induced autism neuron; studies of sufficient statistical power to allow researchers to compare and contrast the effects of autism on the developing human brain; and studies of the influence of environmental factors on these processes. Importantly, all data generated by these investigations will be made widely available to the scientific community. The cells lines themselves will also be made available through the existing CHOC-funded stem cell repository, the NHNSCR, which Dr. Phillip H. Schwartz, Ph.D., created in 2001.

Researchers Coax Bone Marrow Stem Cells To Become Vision Cells

On July 26th we posted about some of the companies working on stem cell solutions for eye diseases.  Now, in what appears to be unique research, bone marrow stem cells have been programmed to repair damaged retinas in mice.  A virus carrying a gene was used to gently push the cultured adult stem cells from mice toward becoming retinal cells. However, only after the stem cells were reintroduced into the mice did they completely transform into the desired vision cells, apparently taking environmental cues from the damaged retinas.

After studying the cell-transformation process, University of Florida researchers were able to bypass the gene manipulation step entirely and instead use chemical compounds that mirrored environmental conditions in the body, thus pointing the stem cells toward their ultimate identities as vision cells.

Scripps Institute Stem Cell Research Team Confirms Chinese Mice From Skin Cells iPS Result

And they did it with improved results.  Since Yamanaka and Thompson independently produced embryonic-like stem cells in late 2007, researchers have tried to confirm pluripotency in these cells by producing live mice. For some reason iPS mouse embryos stopped developing about two-thirds of the way through gestation in these past attempts. This led to concerns that iPS cells might be inferior to embryonic stem cells and hinted that reprogramming with four factors ( Both Ymanaka and Thompson used four factors.  However the factors were slightly different, which also raised questions) might not be the best method to produce pluripotent cell lines from patients.

On July 24 we posted about two separate Chinese research teams that had recently accomplished producing mice from induced pluripotent stem cells. Now scientists from the Scripps Research Institute in San Diego, led by Assistant Professor Kristin Baldwin, Ph.D., have confirmed the Chinese accomplishment but with improved results.

Human Induced Pluripotent Stem Cells Produced Without Inserting Genes

Researchers at Worcester Polytechnic Institute's (WPI) Life Sciences and Bioengineering Center (LSBC) and CellThera, a private company also located at the LSBC, have discovered a way to turn on stem cell genes in human fibroblasts from skin cells without the risks associated with inserting extra genes or using viruses.

Dormant stem cell genes OCT4, SOX2 and NANOG, already in the skin cells, were turned on by lowering the amount of atmospheric oxygen the cells were exposed to and by adding a protein called fibroblast growth factor 2 (FGF2) to the culture medium. FGF2 is a naturally occurring protein that is known to be vital for maintaining the pluripotency of embryonic stem cells.

Furthermore, once the stem cell genes were activated and began expressing proteins, the team found those proteins migrated back into the nucleus of the skin cells, precisely as would occur in induced pluripotent stem cells.  "This was an exciting observation," said Raymond Page, PhD, research assistant professor of biology and biotechnology at WPI. "Having these proteins localize to the nucleus is the first step of reprogramming these cells."

Even more surprising, the team found that the stem cell genes OCT4, SOX2 and NANOG were not completely dormant in untreated skins cells, as was presumed. Those genes were, in fact, sending out messages, but those messages were not being translated into the proteins that do the work of making cells pluripotent. "This was quite unexpected," said Tanja Dominko, DVM, PhD, associate professor of biology and biotechnology at WPI and president of CellThera. "Not only does this data force us to rethink what the true markers of pluripotency may be, it suggests there is a natural mechanism at work in these cells regulating the stem cell gene expression. That opens a whole new line of inquiry."

Adapted from the Worcester Polytechnic Institute announcement.

Questions Raised By Chinese Mice From iPS Cells Experiment; UCLA's Recently Reported iPS vs. Embryonic Cell Differences Is One Of Them

The mainstream press has adopted broad coverage of mice produced from Induced Pluripotent Stem (iPS) cells by two separate Chinese laboratories.  The technique the two teams of Chinese researchers used is called tetraploid complementation. With the tetraploid approach the host cells can form only the placental tissues; all the animal's tissues must come from the iPS cells injected into the blastocyst, or very early embryo.

Until these experiments in China, researchers have never been able to produce living animals via this approach, a result that has created doubts about the true pluripotency of iPS cells. But even with these dramatic results, questions remain, at least one major one suggested by recent research on the differences between iPS and embryonic stem cells conducted at UCLA.

Induced Pluripotent Stem Cells Repair Heart In Mayo Clinic Study

A great deal of work is being done to come up with a method of reverting adult stem cells to an embryonic-like state without making them inherently dangerous in the process. Of course after the adult cells are returned to an embryonic-like state they have to be coaxed into becoming the type of cell that is necessary in the particular regenerative medicine application.

About a month ago a Mayo Clinic study, one that delivered embryonic stem cells to mouse embryos in the earliest stages of development, found that the resulting mice demonstrated a capacity to recover from cardiac injury in adulthood.  According to Mayo this study provides the first evidence that preventive regenerative medicine can successfully be used to treat myocardial infarction through prophylactic intervention.

Mayo researchers injected mouse embryos with embryonic stem cells that had been used to successfully treat ischemic heart disease following heart attack. The resulting animals incorporated between five and 20 percent of labeled stem cell-derived tissue. They were born with no apparent abnormalities, and the tested and control groups had similar overall baseline cardiac disease risk profiles. They also demonstrated similar cardiac performance during the one year follow-up.

Now, In a proof-of-concept study, Mayo researchers have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. In this study, researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those resulting from a heart attack, converting them into stem cells that fix heart damage caused by infarction.

Fate Therapeutics: A Further Look At Academic Stem Cell Researchers And The Private Sector That Will Market Their Results

Academic stem cell research pioneer entree into the world of markets and profit is always a trend worth watching. Today we're taking a quick look at Fate Therapeutics.

Among our Sector Companies, all of which are publicly traded, typically someone has suggested a possibility that business people see as a probability.  From there the emphasis is on obtaining approvals from public agencies, gaining market position, branding, and developing scalability, all toward the end of profitable sales. 

Examples range from companies that raise and spend public investor money primarily on research and development (such as Advanced Cell Technologies, Geron, Osiris and others) to those companies formed to market an already existing product or discovery (Neostem comes to mind here; the company has signed numerous partnership and license agreements, particularly in foreign markets, but has yet to spend money on research).

As research into regenerative medicine and stem cells progresses, capital will continue to seek knowledge, or vice versa, and new companies will enter the potential market place.  Academic researchers will be involved through actual participation in the formation and ongoing policy of the new entity or in an advisory capacity that most probably includes an ownership interest. 

Similarities Between Salamander Limb Regeneration And Stem Cell Repairs Of Damaged Human Muscle?

It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury, a result that seems to relate to a parallel finding in salamander limb regeneration.

“The paired-box genes, Pax3 and Pax7 are involved in the development of the skeletal muscles," explained lead researcher Christoph Lepper, a predoctoral fellow at Carnegie Institution for Science’s Department of Embryology. "It is well established that both genes are needed to produce muscle stem cells in the embryo. A previous student, Alice Chen, studied how these genes are turned on in embryonic muscle stem cells. I thought that if they are so important in the embryo, they must be important for adult muscle stem cells. Using genetic tricks, I was able to suppress both genes in adult muscle stem cells. I was totally surprised to find that the muscle stem cells are normal without them.”

Perhaps coincidentally, perhaps not, the Carnegie finding brings to mind a recent research result from the Max Planck Institute regarding salamanders.  Salamanders regrow lost limbs and Elly Tanaka at Planck has been studying how they do so. Tanaka and colleagues found that salamander regeneration begins when a clump of cells called a blastema forms at the tip of a lost limb. From the blastema come skin, muscle, bone, blood vessels and neurons, ultimately growing into a limb virtually identical to the old one.

But here's the surprise: Rather than having their cellular clocks fully reset and reverting to an embryonic state, cells in the salamanders’ stumps became slightly less mature versions of the cells they’d been before.  In other words they don't revert to pluripotency.

Company Founded By James Thomson Reprograms Blood Cells into Stem Cells

Cellular Dynamics international (CDI), founded by Jamie Thomson and colleagues from the U. of Wisconsin, recently reported generating pluripotent stem cells from very small volumes of ordinary human blood samples. CDI is privately held.  Its stated mission is to "provide drug screening and toxicity testing products based on breakthrough induced pluripotent stem (iPS) cell technology,"

Once the difficulty of current approaches to inducing pluripotency is overcome (reducing time and cost while producing high quality scalability and safety), this development suggests the possibility of a readily obtainable source of pluripotent stem cells from the millions of blood samples in storage at repositories and healthcare institutions worldwide.

New Cedars-Sinai Regenerative Medicine Institute to Emphasize Induced Pluripotent Research

The Cedars Institute will be housed in new state-of-the-art laboratories being constructed especially for stem cell and regenerative medicine research. At the heart of the Institute will be a specialized core facility for the production of Induced pluripotent stem cells.

Clive N. Svendsen, Jamie Thomson associate and joint leader of the widely-respected Stem Cell and Regenerative Medicine Center at the University of Wisconsin, has been named to lead the new unit.  He has quite a resume; one that includes professor of neurology and anatomy at the University of Wisconsin-Madison, and consulting professor at Stanford University. Svendsen’s research focuses on both modeling and treating neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and Parkinson’s disease using a combination of stem cells and growth factors.

Differences Found Between Induced Pluripotent Stem Cells And Embryonic Stem Cells

One of the arguments for federal funding of embryonic stem cells -- in light of the progress being made in Induced Pluripotent Stem Cell technology -- is pretty straight forward.  Researchers have used 'embryonic-like' to describe the result of induced regression on adult cells, usually skin cells. The reason embryonic-like is used is that we have not been sure whether they were identical to embryonic stem cells.  In fact, we don't know enough about how embryonic stem cells become every cell in the body to know exactly what 'embryonic-like' means.

In another example of the kind of end run occasionally taking place in the rapidly expanding stem cell research arena, UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

Medicine's New Toolbox: MIT's View Of Induced Pluripotency's Future

"The past two years have been nothing short of a revolution," says John Dimos, a senior scientist at iZumi Bio. "These cells didn't really exist two years ago. This is all brand-new technology, and it's opening up the potential for brand-new science." The company John is with, Izumi Bio, plans to take advantage of that potential by developing a bank of iPS cells from patients with various diseases and using the cells to screen candidates for drug development.

As a postdoc at Harvard, John Dimos built a cellular model of ALS (amyotrophic lateral sclerosis - Lou Gherig's Disease), making it possible to study a neurodegenerative disease outside an animal for the first time. He and his colleagues collected skin cells from an 82-year-old woman with ALS, reprogrammed them into iPS cells, and directed the cells to differentiate into motor neurons that were genetically identical to the donor's defective cells. "It was the first paper to show that you can use a stem cell to see disease pathology in a petri dish," says Douglas Melton, codirector of the Harvard Stem Cell Institute. "That means you can now study diseases in petri dishes and not in people. That's huge."

An Alternative Route To Induced Pluripotent Stem Cells?

Stanford researchers have found a potential alternative to the current process of Induced Pluripotency in intriguing experiments that bring to mind Bonnie Bassler's important "Quorum Sensing" work at Princeton. We posted about Andras Nagy's more direct work on non-viral induced pluripotency in March of this year.

Mouse muscle cells were fused with human skin cells to create hybrids called heterokaryons. In heterokaryons, the nuclei of each cell type remains distinct, and the influence of one on the nature of the other can be clearly distinguished. Researchers examined the hybrids to see if they began to look and act more like muscle cells, skin cells or something in between.

BioTime Awarded $4.7 Million Research Grant in What Might Be Dr. Micheal West's Greatest Coup Yet

Biotime, Inc. (BTIM), one of our Sector Companies, and its CEO, Dr. Michael West, are to be congratulated.  This $4.7 million grant from the California Institute of Regenerative Medicine couldn't have been better timed if it had been a major part of Biotime's business plan.  The grant will fund research into Biotime's licensed ACTCellerate™ embryonic stem cell technology. The overall objective being to generate tools useful in applying ACTCellerate™ technology to the manufacture of patient-specific therapeutic products, which is where Biotime's business plan was headed anyway except it wasn't clear where the money was going to come from. Until now.

Scientists Identify Key Factors in Heart Cell Creation

For the first time key genetic factors that drive the process of generating new heart cells have been identified by Benoit Bruneau, Ph.D. and his research team at the Gladstone Institute. The team found that a combination of three genes could do the trick. This is the first time any combination of factors has been found to activate cardiac differentiation in mammalian cells or tissues.

"The heart has very little regenerative capacity after it has been damaged," said Dr. Bruneau. "With heart disease the leading cause of death in the Western world, this is a significant first step in understanding how we might create new cells to repair a damaged heart."

Scripps Research Institute Produces Induced Pluripotent Stem Cells Using Recombinant Proteins

Since human adult skin cells were first reprogrammed to an embryonic-like state in November 2007, scientists have been trying to find safer ways to generate stem cells from adult cells—developing methods that require fewer genes, or techniques that can put genes in and then take them out. However, to date all of these have still harbored significant safety concerns due to the nature of the genetic manipulations.

Now a new technique, developed at Scripps, solves one of the most challenging safety hurdles associated with personalized stem cell-based medicine. For the first time it enables scientists to make stem cells in the laboratory from adult cells without genetically altering them.

Breakthrough Produces Parkinson’s Disease Patient-Specific Stem Cells Free Of Reprogramming Genes

Whitehead Institute researchers have developed a novel method to remove potential cancer-causing genes during the reprogramming of skin cells from Parkinson’s disease patients into an embryonic-stem-cell-like state. The resulting induced pluripotent stem (iPS) cells were used to derive dopamine-producing neurons, the cell type that degenerates in Parkinson’s disease patients. This marks the first time researchers have generated human iPS cells that have maintained their embryonic stem-cell-like properties after the removal of reprogramming genes.

All of you familiar with stem cell developments know researchers have been reprogramming adult cells into Induced Pluripotent Cells (iPS) by using viruses to transfer four genes into the cells’ DNA. Although necessary for reprogramming cells, these genes, the known oncogene c-Myc in particular, also have the potential to cause cancer.  In addition, the four genes interact with approximately 3000 other genes in the cell, which may change how the cell functions. Therefore, leaving the genes in successfully reprogrammed cells may cause unintended alterations that limit the cells’ applicability for therapeutic use, for drug screens or to study disease in cell culture.

To solve this problem Whitehead Institute researchers used viruses to transfer the reprogramming genes and a gene coding for the enzyme Cre into skin cells from Parkinson’s disease patients. The reprogramming genes were bracketed by short DNA sequences, called loxP, which are recognized by the enzyme Cre.

The Challenge Faced By Our Stem Cell Sector Research Companies

Our Stem Cell Sector consists by definition of either small or micro cap companies, most of which are involved in basic research toward producing a scalable, off-the-shelf product, or line of products, developed from adult or embryonic stem cells for use in either direct medical therapies, or in basic research by academic or other corporate institutions.  If they're not doing this, or in some cases even if they are, they're coming up with media and reagents that assist in such product development or research.

Companies researching stem cell therapies, whether from embryonic or adult cells, must cause their chosen stem cell to differentiate (change) into a specific type of cell necessary for the sought after therapy.  This is done by finding the right set of culture conditions (these consist of combinations of proteins, environmental factors, temperatures, salts, etc.) that change specific cell types into cells that cure targeted diseases or effect desired tissue repairs. 

Regenerative Medicine And Stem Cells, A Summary

Cell sources used to rebuild damaged tissues are the major issue in the development of regenerative medicine.  Three sources of cells can be tapped for transplant: differentiated tissues (refers to a technique developed at Harvard and posted here in August 2008, a better approach to the production of Induced Pluripotent Stem Cells), adult stem cells (ASCs) and derivatives of embryonic stem cells (ESCs). Adult stem cells regenerate epithelia, brain tissue, muscle, blood and bone. They have also been found in other tissues that normally scar after injury, such as myocardium, spinal cord and retinal tissues.

Advances Announced In Quest To Eliminate Retroviruses From iPS Process

As B.D. Colen put it in the Harvard Science story: "Imagine, if you can, a day within the next decade when a physician-scientist could remove a skin cell from your arm, and with a few chemicals turn that fully formed adult cell into a dish of stem cells genetically matched to you."

Eliminating the use of genes, and the viruses being used to insert them into target cells, is a goal of scientists doing reprogramming work, because the genes become integrated into the genome of the target cells and may change them in ways not yet understood or anticipated.

Dramatic Changes In DNA Caused By Stem Cell Specialization

As embryonic stem cells turn into different cell types, there are dramatic corresponding changes to the order in which DNA is replicated and reorganized.

These findings bridge a critical knowledge gap for stem cell biologists, enabling a better understanding of  the enormously complex process by which DNA is repackaged during differentiation -- when embryonic stem cells lose their functionally virgin status and become specialized  in function.

Plurinet: A New Strategy For Classifying Stem Cells By Their Molecular Machinery

Using a collection of about 150 human cell samples, researchers have revealed a protein-protein network common to pluripotent cells. Dubbed Plurinet, this network points to what may be one of the key building blocks of the machinery that enables these transformative cells to differentiate into multiple cell types.

"Our results offer a new strategy for classifying stem cells by their molecular machinery," said professor Jeanne Loring, Ph.D., director of the Center for Regenerative Medicine at Scripps Research Institute, who pursued this work along with an international team of researchers. "We show that pluripotence and self-renewal are under tight control by specific molecular networks."

Yamanaka Confirms Harvard Results, Produces iPS Cells Without Using Retroviruses

Shinya Yamanaka MD, PhD, of Kyoto University and the Gladstone Institute of Cardiovascular Disease (GICD) has produced Induced Pluripotent Stem Cells (iPS) without employing retroviruses in the process. In doing so he has taken another step toward the practical application of iPS cells and has confirmed research done at the Harvard Stem Cell Institute posted here recently.

Yamanaka's lab at Kyoto was the first to create human induced pluripotent stem cells (iPS) from adult skin cells in November of 2007.  The work was confirmed by almost simultaneous results obtained by James Thomson's lab at the University of Wisconsin.  The problem was that the reprogramming process used by each lab required the introduction of retroviruses which held the possibility of introducing cancer.

Induced Pluripotent Stem Cells Produced Without Using Retroviruses

Excitement over the ability of researchers to create Induced Pluripotent Stem Cells (iPS) by inserting four genes into adults cells has thus far been tempered by the fact that the genes have been inserted using retroviruses, which have the potential to turn on cancer genes and trigger tumor growth.

In late August we posted that Harvard Stem Cell Institute researchers had turned mouse exocrine cells, which make up about 95 percent of the pancreas, into precious and rare insulin-producing beta cells, and had done so without returning the cells to an embryonic state, using only three genes.

Epigenetics Map To Assist Development Of Induced Pluripotent Stem Cells

Epigenetic code is a series of chemical switches added onto DNA to ensure cells can form different types of tissue (for example liver and skin) despite having identical DNA genetic code.

When DNA is copied from cell to cell, it is essential that the epigenetic code is copied accurately. If not, a liver progenitor cell may divide into another type of cell, such as a nerve or eye cell. A breakdown in this system might also mean that a gene for cell growth is accidentally switched on, for example, leading to unregulated cell growth and the development of tumors.

Kyoto University Receives Japanese Patent On Induced Pluripotent Stem Cells, Applies in U.S.

Kyoto University today announced that it has obtained a patent in Japan on the basics for a method of creating induced pluripotent stem (iPS) cells.  Induced Pluripotent Stem Cells are the result of reprogramming adult cells into a stem cell like state using a method that introduces a small number of genes into the the cells.  Once the cells are reprogrammed it is thought they can be converted to any other cell in the body.

On The Horizon: The Holy Grail Of Stem Cell Research?

We are in the early and rapidly changing stage in Induced Pluripotent Stem (iPS) cell development.  Until now, most research effort has been directed toward finding a way to introduce genes into an adult cell in order to return it to an embryonic stem cell state.

The step that isn't talked about much is the next one: after the cell is returned to an embryonic state it must then be coaxed or directed to become the type of cell needed in the therapeutic process or application.  The holy grail of Induced pluripotent stem cell development would be to change an abundant adult cell into the type of cell needed in the patient's body.  And the holiest of all grails would be to do it without removing the cell from the patient. 

University of Wisconsin Establishes Induced Pluripotent Stem Cell Bank

The University of Wisconsin and stem cell pioneer James Thomson have started the first induced pluripotent stem cell bank, thus cementing - yet another time - their position as a leader in stem cell research and regenerative medicine.

"We are establishing the WiCell Bank to grow, test, store and distribute cell lines that the National Stem Cell Bank currently is unable to offer since it is limited to the 21 human embryonic stem cell lines approved for federal funding," stated Erik Forsberg, executive director of the WiCell Research Institute, a not-for-profit U of W support organization which already hosts the National Stem Cell Bank for the National Institutes of Health under a federal contract.

Protein Substitute Advances Reprogramming Of Adult Cells Into Induced Pluripotent Cells

Whitehead Institute researchers have replaced the gene c-Myc and its retrovirus with a naturally occurring signaling molecule called Wnt3a. When added to the fluid surrounding the cells being reprogrammed, Wnt3a promotes the conversion of adult cells into Induced Pluripotent Stem cells.

Currently, IPS cells can be created by reprogramming adult cells through the use of viruses to reintroduce four genes (Oct4, Sox2, c-Myc and Klf4) into an adult cell's DNA.  These four genes were employed by Yamanka's team to reprogram human skin cells last November.  Thomson's team at Wisconsin, in independently creating the same result, used NANOG and LIN28 instead of c-Myc and Klf4.  Later, Dr. Thomas Zwaka at the Baylor College of Medicine found that another gene, Ronin, could substitute for Oct4 and perhaps some of the other genes as well. Oct4, Sox2 and Nanog have been thought to be the major regulators of embryonic stem cells.  According to Zwaka, Ronin may be as important as these three.

Do Some Adult Cells Revert To An Embryonic State Of Their Own Accord?

Fruit flies, or Drosophila, have a long and illustrious history as laboratory guinea pigs. Now it turns out these lowly lab creatures are challenging one of the basic paradigms of stem cell research, that being the belief that the ability to form new cell types or tissues diminishes as a cell becomes more specialized.

Researcher Molly Weaver was simply investigating how the respiratory system of the fly is remodeled when the animal transforms from a tiny, grub-like larva into a full-fledged, winged fly lusting after bananas and apples.  What she found was a surprise: Specialized cells, she determined, naturally regress to serve as a kind of de facto stem cell during the fruit-fly life cycle.

Thomson Team Will Attempt To Answer A Fundamental Mystery Of Stem Cell Biology

Scientists have had access to human embryonic stem cells for a decade. But precisely how this all-purpose cell gives rise to all other cells in the body remains a fundamental mystery of biology.

Now, an $8.9 million grant from the National Institute of General Medical Sciences (NIGMS) will allow a team of researchers from the University of Wisconsin-Madison to embark on a five year quest to find the secrets of a stem cells' ability to morph into all of the cell types that make up the body.