Stem Cell Clinic

Growing human GI cells may lead to personalized treatments

A method of growing human cells from tissue removed from a patient's gastrointestinal (GI) tract eventually may help scientists develop tailor-made therapies for inflammatory bowel disease and other GI conditions.

Reporting online recently in the journal Gut, researchers at Washington University School of Medicine in St. Louis said they have made cell lines from individual patients in as little as two weeks. They have created more than 65 such cell lines using tissue from 47 patients who had routine endoscopic screening procedures, such as colonoscopies. A cell line is a population of cells in culture with the same genetic makeup.

The scientists said the cell lines can help them understand the underlying problems in the GI tracts of individual patients and be used to test new treatments.

"While it has been technically possible to isolate intestinal epithelial stem cells from patients, it has been challenging to use the material in ways that would benefit them on an individual basis," said co-senior investigator Thaddeus S. Stappenbeck, MD, PhD, a professor of pathology and immunology. "This study advances the field in that we have developed new methods that allow for the rapid expansion of intestinal epithelial stem cells in culture. That breaks a bottleneck and allows us to develop new ways to test drug and environmental interactions in specific patients."

To grow the human cells, the researchers adapted a system used to grow intestinal epithelial stem cells in mice. In the GI tract, epithelial cells line the inner surface of the esophagus, stomach and intestines.

"An additional important feature of this system is that we can isolate stem cell lines from intestinal biopsies," said first author Kelli L. VanDussen, PhD, a postdoctoral fellow in Stappenbeck's laboratory. "These biopsies are very small tissue fragments that are routinely collected by a gastroenterologist during endoscopy procedures. We have refined this technique, so we have nearly 100 percent success in creating cell lines from individual patient biopsies."

The researchers developed an experimental system that created high levels of critical factors to isolate and expand intestinal epithelial stem cells, including a signaling protein called Wnt and a related protein called R-spondin, which enhances the Wnt signal. They also exposed the cells to a protein called Noggin, which prevented the cells from differentiating into other cell types that live in the GI tract.

After growing the intestinal cell lines, the investigators collaborated with Phillip I. Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics and director of the Division of Pediatric Gastroenterology and Nutrition, to conduct experiments and see how the cells interacted with bacterial pathogens like E. coli.

This showed that pathogenic strains of E. coli attached to intestinal epithelial cells. That attachment is thought to be the critical step in stimulating disease. The investigators said the experimental system they created should lead to new methods to uncover therapies for treating bacterial infections of the intestine.

"In the past, the only really robust method for studying GI epithelial cells was to use cancer cell lines," said co-senior investigator Matthew A. Ciorba, MD, a gastroenterologist and assistant professor of medicine. "However, cancer cells behave differently than the noncancerous GI epithelium, which is affected in patients with conditions such as inflammatory bowel disease. This technique now allows us to study cells identical to the ones that live in a patient's GI tract. Plus, we can grow the cell lines quickly enough that it should be possible to develop a personalized approach to understanding a patient's disease and to tailor treatment based on a patient's underlying problem."

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Growing human GI cells may lead to personalized treatments

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PHYTOSCIENCE PHILIPPINES DOUBLE SKIN CELL THERAPY REVIEW - Video

BioEden fights the financial cost of stem cell banking by bringing their specialist service to the people for just 5 …

(PRWEB UK) 7 August 2014

BioEden the specialist tooth stem cell bank stands by its pledge to make personalised stem cell therapy an affordable reality by launching Access Membership at just 5 per month.

With stem cell therapy holding the promise of longer and better lives in the future, the cost and the ease of finding a stem cell match has been an issue, given that the cost of private stem cell banking requires an initial cash outlay of up to 4000.

Not any more.

BioEden the leading specialist tooth stem cell bank, has added Access Membership to parents finding themselves financially unable to bank their child's cells for future use. "It doesnt sit well with us that a parent could be unable to access what could be a life saving service for their child, for financial reasons," said Group CEO Mr Tony Veverka.

Parents can access the stem cell banking service for just 5 per month, and can become a member of the plan as soon as the baby is born. To date the option for stem cell banking at birth has been umbilical cord blood banking, an invasive process which provides haemopoetic stem cell banking at a cost.

Now parents have the option to choose tooth stem cell banking or to add this to cord blood banking at a very low monthly cost.

Tooth stem cells have considerable advantages over cord blood cells;

And now, thanks to BioEden, cost doesnt have to be a barrier.

So how can 5 a month give access to such a specialist service?

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BioEden fights the financial cost of stem cell banking by bringing their specialist service to the people for just 5 ...

Single-Cell Analysis Holds Promise for Stem Cell and Cancer Research

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Newswise UC San Francisco researchers have identified cells unique features within the developing human brain, using the latest technologies for analyzing gene activity in individual cells, and have demonstrated that large-scale cell surveys can be done much more efficiently and cheaply than was previously thought possible.

We have identified novel molecular features in diverse cell types using a new strategy of analyzing hundreds of cells individually, said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. We expect to use this approach to help us better understand how the complexity of the human cortex arises from cells that are spun off through cell division from stem cells in the germinal region of the brain.

The research team used technology focused on a microfluidic device in which individual cells are captured and flow into nano-scale chambers, where they efficiently and accurately undergo the chemical reactions needed for DNA sequencing. The research showed that the number of reading steps needed to identify and spell out unique sequences and to successfully identify cell types is 100 times fewer than had previously been assumed. The technology, developed by Fluidigm Corporation, can be used to individually process 96 cells simultaneously.

The routine capture of single cells and accurate sampling of their molecular features now is possible, said Alex Pollen, PhD, who along with fellow Kriegstein-lab postdoctoral fellow Tomasz Nowakowski, PhD, conducted the key experiments, in which they analyzed the activation of genes in 301 cells from across the developing human brain. Their results were published online August 3 in Nature Biotechnology.

Kriegstein said the identification of hundreds of novel biomarkers for diverse cell types will improve scientists understanding of the emergence of specialized neuronal subtypes. Ultimately, the combination of this new method of focusing on gene activity in single cells with other single-cell techniques involving microscopic imaging is likely to reveal the origins of developmental disorders of the brain, he added.

The process could shed light on several brain disorders, including lissencephaly, in which the folds in the brains cortex fail to develop, as well as maladies diagnosed later in development, such as autism and schizophrenia, Kriegstein said.

According to the Nature Biotechnology study co-authors, this strategy of analyzing molecules in single cells is likely to find favor not only among researchers who explore how specialized cells arise at specific times and locations within the developing organism, but also among those who monitor cell characteristics in stem cells engineered for tissue replacement, and those who probe the diversity of cells within tumors to identify those responsible for survival and spread of cancerous cells.

No matter how pure, in any unprocessed biological sample there are a variety of cells representing various tissue types. Researchers have been sequencing the combined genetic material within these samples. To study which genes are active and which are dormant, they use the brute repetition of sequencing steps to capture an adequate number of messenger RNA sequences, which are transcribed from switched-on genes. However, it is difficult to conclude from mixed tissue samples which genes are expressed by particular cell types.

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Single-Cell Analysis Holds Promise for Stem Cell and Cancer Research

Researchers seek 'safety lock' against tumor growth after stem cell transplantation

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6-Aug-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Aug. 6, 2014) Recent studies have shown that transplanting induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) can promote functional recovery after spinal cord injury in rodents and non-human primates. However, a serious drawback to the transplantation of iPS-NSCs is the potential for tumor growth, or tumorogenesis, post-transplantation.

In an effort to better understand this risk and find ways to prevent it, a team of Japanese researchers has completed a study in which they transplanted a human glioblastoma cell line into the intact spinal columns of laboratory mice that were either immunodeficient or immunocompetent and treated with or without immunosuppresant drugs. Bioluminescent imaging was used to track the transplanted cells as they were manipulated by immunorejection.

The researchers found that the withdrawal of immunosuppressant drugs eliminated tumor growth and, in effect, created a 'safety lock' against tumor formation as an adverse outcome of cell transplantation. They also confirmed that withdrawal of immunosuppression led to rejection of tumors formed by transplantation of induced pluripotent stem cell derived neural stem/progenitor cells (iPS-NP/SCs).

Although the central nervous system has shown difficulty in regenerating after damage, transplanting neural stem/progenitor cells (NS/PCs) has shown promise. Yet the problem of tumorogenesis, and increases in teratomas and gliomas after transplantation has been a serious problem. However, this study provides a provisional link to immune therapy that accompanies cell transplantation and the possibility that inducing immunorejection may work to reduce the likelihood of tumorogenesis occurring.

"Our findings suggest that it is possible to induce immunorejection of any type of foreign-grafted tumor cells by immunomodulation," said study co-author Dr. Masaya Nakamura of the Keio University School of Medicine. "However, the tumorogenic mechanisms of induced pluripotent neural stem/progenitor cells (iPS-NS/PCs) are still to be elucidated, and there may be differences between iPS-NS/PCs derived tumors and glioblastoma arising from genetic mutations, abnormal epigenetic modifications and altered cell metabolisms."

The researchers concluded that their model might be a reliable tool to target human spinal cord tumors in preclinical studies and also useful for studying the therapeutic effect of anticancer drugs against malignant tumors.

"This study provides evidence that the use of, and subsequent removal of, immunosuppression can be used to modulate cell survival and potentially remove tumor formation by transplanted glioma cells and provides preliminary data that the same is true for iPS-NS/PCs." said Dr. Paul Sanberg, distinguished professor at the Center of Excellence for Aging and Brain Repair, University of South Florida. "Further study is required to determine if this technique could be used under all circumstances where transplantation of cells can result in tumor formation and its reliability in other organisms and paradigms."

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Researchers seek 'safety lock' against tumor growth after stem cell transplantation

Star Scientist Embroiled in Controversy Found Dead in Apparent Suicide

The stem-cell research community reels after Yoshiki Sasai, a famous name in regenerative medicine, is found dead on August 5

Yoshiki Sasai. Credit: Nick Higgins

Scientists around the world are struggling to get to grips with the loss of one of the brightest stars in stem-cell science. Yoshiki Sasai of the RIKEN Center for Developmental Biology (CDB) in Kobe brought excitement and rigour to the field but died yesteday, August 5, aged 52. The reasons for Sasais apparent suicide are still not clear but a scandal swirling about two stem-cell papers published inNaturein January had wreaked havoc on his career.

Dr. Sasai was a rigorous and innovative scientist and his loss will be deeply felt, saysJanet Rossantat the Hospital for Sick Children in Toronto, Canada, a former head of the International Society for Stem Cell Research. His most important contributions to the stem-cell field came from his background in developmental biology.

Sasais research spanned developmental biology, stem cells, organogenesis and tissue engineering. His success was built on his painstaking efforts to understand exactly which factors needed to be added or removed to cell cultures to guide embryonic stem cells as they differentiated to mature cell types,especially neuronal cells.

He sees things that others dont see,Eddy De Robertistold Naturein a 2012 interview. De Robertis, a developmental biologist at the University of California, Los Angeles, who supervised Sasais postdoctoral work in the mid 1990s, recalled Sasai once retyping a manuscript lost in a computer from memory with word-for-word perfection. Id never seen anything like that, he said.

Lab-grown cortex One of Sasais innovations was thediscovery in 2007of a pharmacological compound that kept embryonic stem cells from dying when separated from each other. Previously, embryonic stem cells had to be manually cut with a cumbersome method and transferred as partial colonies, which resulted in experimental variation. His paper solved that overnight, saysLuc Leynsof the Vrije Universiteit in Brussels.

But Sasai's show-stoppers came shortly after that. Based on his success in differentiating neurons, Sasai started mimicking embryonic development with such fidelity that his cells would organize themselves into three-dimensional structures, including agoblet-shaped clump of retinal tissue known as an optic cupandintricate layers of tissue that resembled a cerebral cortex.

Both these discoveriesopened the field ofin vitrobrain organogenesis. Finally, we have easy access to the developing brain without having to micro dissect embryos, says Leyns. Leyns says he uses Sasais papers to show masters students how a modern scientific discovery is made and progressively built-up to a climax.

Sasais work was inspirational, says Pete Coffey of University College London, where Sasai presented the optical cup research last November. The clarity of his presentation, the excitement and post lecture discussions with fellows and students are still discussed today. He had a major impact on my group, says Coffey. Sasais research will probably contribute to treatments for various disorders, such as macular degeneration. His findings galvanized the ophthalmology community in truly developing a cell therapy for blinding disorders, says Coffey.

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Star Scientist Embroiled in Controversy Found Dead in Apparent Suicide