Thursday, 17 July 2014

Umbilical Cord Blood, at the Cutting Edge of Today’s Medicine

“Saving Grace”
From: Al Jazeera America’s TECHKNOW Presents
Thursday, 17 July 2014

This Saturday, July 19th at 7:30 pm ET/4:30 pm PT, Al Jazeera America’s “TechKnow” shows us one of the most exiting areas of medical research – how umbilical cord blood is being used to treat brain disease and injury.

Dr. Joanne Kurtzberg. Credit: Al Jazeera.
“Techknow” host and mechanical engineer Dr. Shini Somara takes us inside Duke Children’s Hospital, where a team of doctors is treating young Grace Matthews, an infant with hydrocephalus, or water on the brain, characterized by the tell-tale swelling of the baby’s head.  We go behind-the-scenes on the high-tech experimental treatments, as doctors infuse Grace with stem cells from her own umbilical cord, and we meet another young patient who experienced “miraculous” progress from the use of umbilical cord stem cells.

The medical equivalent of gold, we’re just at the tip of understanding how stem cells from cord blood, harvested at the time of birth, can be used to help the brain regenerate and heal from injuries and damage.

“I personally believe cell therapy, and regenerative medicine, is going to be the next big advance in medicine, and that cells like cord blood are going to drive that forward,” reports Dr. Joanne Kurtzberg, Chief of the Division of Pediatric Blood and Marrow Transplantation at Duke University Medical Center in Durham, North Carolina.

The program is airing Saturday, July 19th at 7:30PET/4:30P PT;
Repeats 10:30P ET/7:30P PT

Find Al Jazeera America near you: www.aljazeera.com/getajam

About Al Jazeera America’s “TechKnow”:
Al Jazeera America’s “TechKnow” is a half hour documentary show that airs weekly on Saturdays at 7:30 pm ET/4:30 pm PT.  A show about innovations that can change lives, “TechKnow” explores the intersection of hardware and humanity in a unique way – it’s a show about science, by scientists. “TechKnow” rotating cast of hosts includes mechanical engineer Dr. Shini Somara, molecular neuroscientist Dr. Crystal Dilworth, entolomologist Phil Torres, biologist Marita Davison, engineer Kosta Grammatis, science writer Kyle Hill, former CIA operative and analyst Lindsay Moran, neuroscientist Rachelle Oldmixon and neurobiologist Cara Santa Maria.

Source: Al Jazeera America’s “TechKnow
Contact: Jocelyn Austin, Director, Publicity
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Thursday, 3 July 2014

Some Stem Cell Methods Closer to "Gold Standard" than Others

Nuclear transfer appears superior for creating embryonic stem cells
Thursday, 03 July 2014

Researchers around the world have turned to stem cells, which have the potential to develop into any cell type in the body, for potential regenerative and disease therapeutics.

Now, for the first time, researchers at the Salk Institute, with collaborators from Oregon Health & Science University and the University of California, San Diego, have shown that stem cells created using two different methods are far from identical. The finding could lead to improved avenues for developing stem cell therapies as well as a better understanding of the basic biology of stem cells.

The researchers discovered that stem cells created by moving genetic material from a skin cell into an empty egg cell — rather than coaxing adult cells back to their embryonic state by artificially turning on a small number of genes — more closely resemble human embryonic stem cells, which are considered the gold standard in the field.

Joseph R. Ecker, Professor, Genomic Analysis
Laboratory. Credit: Courtesy of the Salk
Institute for Biological Studies. 
"These cells created using eggs' cytoplasm have fewer reprogramming issues, fewer alterations in gene expression levels and are closer to real embryonic stem cells," says co-senior author Joseph R. Ecker, professor and director of Salk's Genomic Analysis Laboratory and co-director of the Center of Excellence for Stem Cell Genomics. The results of the study were published today in Nature.

Human embryonic stem cells (hESCs) are directly pulled from unused embryos discarded from in-vitro fertilization, but ethical and logistical quandaries have restricted their access. In the United States, federal funds have limited the use of hESCs so researchers have turned to other methods to create stem cells. Most commonly, scientists create induced pluripotent stem (iPS) cells by starting with adult cells (often from the skin) and adding a mixture of genes that, when expressed, regress the cells to a pluripotent stem-cell state. Researchers can then coax the new stem cells to develop into cells that resemble those in the brain or in the heart, giving scientists a valuable model for studying human disease in the lab.

Over the past year, a team at OHSU built upon a technique called somatic cell nuclear transfer (the same that is used for cloning an organism, such as Dolly the sheep) to transplant the DNA-containing nucleus of a skin cell into an empty human egg, which then naturally matures into a group of stem cells.

Shoukhrat Mitalipov, Ph.D., Oregon Health &
Science University, led a team that found that a
process called "somatic cell nuclear transfer" is
much better and more accurate at
reprogramming human skin cells to become
embryonic stem cells. Credit: Oregon Health &
Science University.
Ecker, holder of the Salk International Council Chair in Genetics, teamed up with Shoukhrat Mitalipov, developer of the new technique and director of the Center for Embryonic Cell and Gene Therapy at OHSU, and UCSD assistant professor Louise Laurent to carry out the first direct comparison of the two approaches. The scientists created four lines of nuclear transfer stem cells all using eggs from a single donor, along with seven lines of iPS cells and two lines of the gold standard hESCs. All cell lines were shown to be able to develop into multiple cell types and had nearly identical DNA content contained within them.

But when they looked closer at the cells, the researchers spotted some differences: the patterns of methylation — chemical flags that are added to genes to control their expression — varied between the cell lines. This indicates a difference in how and when genes, despite having identical sequences, might be expressed. The methylation of nuclear transfer cells more closely resembled hESCs than the iPS cells did. And when the investigators looked at patterns of actual gene expression — by measuring the levels of particular RNA strands produced by each cell — the differences continued. Once again, nuclear transfer cells had RNA levels closer to embryonic cells, making them more accurate for basic research and therapeutic studies.

"Both the DNA methylation and gene expression data show that nuclear transfer does a better job at erasing the signature of the original skin cell," says Laurent, who is a co-senior author of the paper.

"If you believe that gene expression is important, which we do, then the closer you get to the gene expression patterns of embryonic stem cells, the better," Ecker says.

"Right now, nuclear transfer cells look closer to the embryonic stem cells than do the iPS cells."

Ecker doesn't expect labs to race to make the switch to nuclear transfer protocols — after all, the method falls within those restricted for federal funding. But he thinks the new observation likely holds lessons that could help improve the protocols for making iPS cells.

"What this is telling us is that you can use the standard mix of genes and they do a pretty good job of creating iPS cells," Ecker says.

"But they're not perfect. The material in an egg does a better job than just those four genes alone."

If researchers can pin down what it is within an egg that drives the production of pluripotent stem cells, they may be able to integrate that knowledge into iPS methods to improve stem cell therapy for disease.

"At this point, nuclear transfer stem cells combine the key advantages of both hESCs and iPS cells and, as such, are ideal for clinical applications in regenerative therapy," adds Mitalipov.

Other researchers on the study were Ryan C. O'Neil, Yupeng He, Matthew D. Schultz, Manoj Heriharan, Joseph R. Nery, and Rosa Castanon of the Salk Institute for Biological Studies; Hong Ma, Brittany Daughtry, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed, Nuria Marti Gutierrez, Crystal Van Dyken, Alimujiang Fulati, Atsushi Sugawara, Michelle Sparman, Paula Amato and Don P. Wolf of Oregon Health & Science University; Robert Morey, Karen Sabatini and Rathi D. Thiagarajan of the University of California, San Diego; and Sumita Gokhale of the Boston University School of Medicine.

Contact: Kristina Grifantini

Reference:
Abnormalities in human pluripotent cells due to reprogramming mechanisms
Hong Ma, Robert Morey, Ryan C. O'Neil, Yupeng He, Brittany Daughtry, Matthew D. Schultz, Manoj Hariharan, Joseph R. Nery, Rosa Castanon, Karen Sabatini, Rathi D. Thiagarajan, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed, Nuria Marti Gutierrez, Crystal Van Dyken, Alim Polat, Atsushi Sugawara, Michelle Sparman, Sumita Gokhale, Paula Amato, Don P.Wolf, Joseph R. Ecker, Louise C. Laurent & Shoukhrat Mitalipov
Nature (2014), doi:10.1038/nature13551
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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/

Tuesday, 1 July 2014

'Master Switch' for Myelination in Human Brain Stem Cells is Identified

Finding is key to developing MS treatments using stem cells
Tuesday, 01 July 2014

The identification of the transcription factor,
SOX10, in human brain cells, brings researchers
closer to the goal of treating multiple sclerosis
(MS) by transplanting into patients the brain cells
that make myelin. Credit: Jing Wang. 
Scientists at the University at Buffalo have identified the single transcription factor or "master switch" that initiates the critical myelination process in the brain. The research will be published online in Proceedings of the National Academy of Sciences (PNAS) on June 30.

The identification of this factor, SOX10, in human brain cells, brings researchers closer to the goal of treating multiple sclerosis (MS) by transplanting into patients the brain cells that make myelin.

"Now that we have identified SOX10 as an initiator of myelination, we can work on developing a viral or pharmaceutical approach to inducing it in MS patients," says Fraser Sim, PhD, senior author on the paper and assistant professor in the UB Department of Pharmacology and Toxicology in the School of Medicine and Biomedical Sciences.

"If we could create a small molecule drug that would switch on SOX10, that would be therapeutically important," he adds.

Stem cell therapy is seen as having dramatic potential for treating MS, but there are key obstacles, especially the length of time it takes for progenitor cells to turn into oligodendrocytes, the brain's myelin-making cells.

Using currently available methods, Sim explains, it can take as long as a year to generate a sufficient number of human oligodendrocyte cells to treat a single MS patient.

That's partly because there are so many steps: the skin or blood cell must be turned into induced pluripotent stem cells, which can differentiate into any other type of cell and from which neural progenitor cells can be produced. Those progenitor cells then must undergo differentiation to oligodendrocyte progenitors that are capable of ultimately producing the oligodendrocytes.

"Ideally, we'd like to get directly to oligodendrocyte progenitors," says Sim.

"The new results are a stepping stone to the overall goal of being able to take a patient's skin cells or blood cells and create from them oligodendrocyte progenitors," he says.

Using foetal (not embryonic) brain stem cells, the UB researchers searched for transcription factors that are absent in neural progenitor cells and switched on in oligodendrocyte progenitor cells.

While neural progenitor cells are capable of producing myelin, they do so very poorly and can cause undesirable outcomes in patients, so the only candidate for transplantation is the oligodendrocyte progenitor.

"The ideal cell to transplant is the oligodendrocyte progenitor cell," Sim says.

"The question was, could we use one of these transcription factors to turn the neural progenitor cell into an oligodendrocyte progenitor cell?"

To find out, they looked at different characteristics, such as mRNA expression, protein and whole gene expression and functional studies.

"We narrowed it down to a short list of 10 transcription factors that were made exclusively by oligodendrocyte progenitor cells," says Sim.

"Among all 10 factors that we studied, only SOX10 was able to make the switch from neural progenitor to oligodendrocyte progenitor cell," says Sim.

In addition, the UB researchers found that SOX10 could expedite the transformation from oligodendrocyte progenitor cell to differentiation as an oligodendrocyte, the myelin-producing cell and the ultimate treatment goal for MS.

"SOX10 facilitates both steps," says Sim.

That's tantalizing, he says, because one of the biggest problems with MS is that cells get stuck in the step between the oligodendrocyte progenitor cell and the oligodendrocyte.

"In MS, first the immune system attacks the brain, but the brain is unable to repair itself effectively," explains Sim.

"If we could boost the regeneration step by facilitating formation of oligodendrocytes from progenitor cells, then we might be able to keep patients in the relapsing remitting stage of MS, a far less burdensome stage of disease than the later, progressive stage."

Sim is also an investigator with other scientists at UB and the University of Rochester on the $12.1 million New York State Stem Cell Science award led by SUNY Upstate Medical Center. The research will test the safety and effectiveness of implanting stem cells that can reproduce myelin into the central nervous system of MS patients.

Contact: Ellen Goldbaum
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