Patients Own Stem Cells Help Stroke Victim

UT Houston researchers will enrol 10 patients in phase I trial Thursday, 16 April 2009 For the first time in the United States, a stroke patient has been intravenously injected with his own bone marrow stem cells as part of a research trial at the University of Texas Medical School at Houston. Roland "Bud" Henrich, 61, was transferred to Memorial Hermann – Texas Medical Center on March 25 after suffering a stroke while working on his farm in Liberty. He arrived too late to receive tissue plasminogen activator (tPA), the only treatment for ischemic strokes. He became the first patient in the trial. The Phase I safety trial, funded with a pilot grant from The National Institutes of Health and support from the Notsew Orm Sands Foundation, will enrol nine more patients who have suffered a stroke and can be treated with the stem cell procedure within 24 to 72 hours of initial symptoms. Stroke occurs when a blockage or a rupture in an artery, depriving brain tissue of oxygen, interrupts blood flow to the brain. It is the third-leading cause of death behind heart disease and cancer. According to the American Stroke Association, nearly 800,000 Americans suffer a stroke each year – one every 40 seconds. On average, someone dies of stroke every three to four minutes. "It's still very early in this safety study, but this could be an exciting new therapeutic approach for people who have just suffered a stroke," said Sean Savitz, M.D., assistant professor of neurology at the medical school and the study's lead investigator. "Animal studies have shown that when you administer stem cells after stroke, the cells enhance the healing. We know that stem cells have some kind of guidance system and migrate to the area of injury. They're not making new brain cells but they may be enhancing the repair processes and reducing inflammatory damage." Savitz said animal studies have shown that the healing effects of stem cells can occur as early as a week but cautioned it is too early to attribute Henrich's improvement to the stem cell treatment. "I'm hoping he will get better and it will be because of the cells, but it's just hope at this point," Savitz said. The stem cells were harvested from the bone marrow in the iliac crest of his leg, then separated and returned to Henrich several hours later. Because they are his own stem cells, rejection is not expected to be an issue. When he arrived at the hospital, Henrich could not speak and had significant weakness on his right side. When he was released after nearly two weeks of hospitalization and rehabilitation, he was able to walk and climb stairs unassisted and said his first words. His wife, Reba Henrich, said she believes the stem cells have helped. He has spoken a few times with a single word or a phrase since his return home. "Too crowded," he told her at a megastore as they shopped for Easter gifts for their grandchildren and "senior" meal he told a waitress at a local restaurant. He also has fed the cows by himself, she said. They are hopeful he will eventually be able to return to his job as a painter. "This study is the critical first step in translating laboratory work with stem cells into benefit for patients. If effective, this treatment could be helpful to a huge segment of stroke patients to reduce their disability," said James C. Grotta, M.D., Roy M. and Phyllis Gough Huffington Distinguished Professor of Neurology and chair of the Department of Neurology at the medical school. "We are fortunate here at UT Houston and the Texas Medical Center to have the resources needed to carry out this work, and to have attracted someone of Dr. Savitz's calibre to lead this study." ......... ZenMaster

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Novel Technique to Sequence Human Genome

Physicists at Brown University have developed a novel procedure to map a person’s genome Thursday, 16 April 2009 Since the human genome was sequenced six years ago, the cost of producing a high-quality genome sequence has dropped precipitously. More recently, the National Institutes of Health called for cutting the cost to $1,000 or less, which may enable sequencing as part of routine medical care. The obstacles to reaching that goal have been primarily technological: Scientists have struggled to figure out how to accurately read the 3 billion base pairs – the amount of DNA found in humans and other mammals – without time-consuming, inefficient methods. Physicists at Brown University may have an answer. They introduce a novel procedure to vastly slow the DNA's movement through openings that are used to read the code. In the journal Nanotechnology, the physicists report the first experiment to move DNA through a solid-state nanopore using magnets. The approach is promising because it allows multiple segments of a DNA strand to be threaded simultaneously through numerous tiny pores and for each fragment to move slowly enough through the opening so that the base pairs can be accurately read. "When it comes to sequencing anyone's genome, you need to do it cheaply, and you need to do it quickly," explained Xinsheng Sean Ling, professor of physics, who joined the Brown faculty in 1996. "This is a step in that direction." The idea of reading DNA by threading strands through tiny openings is not new. Scientists have shown that an applied electric field can drive the DNA molecules through a nanopore, a tiny hole in a membrane. But in those experiments, the base pairs moved too quickly through the openings for the code to be read accurately. So, while a large electric field is needed to draw the DNA molecules into the pore, Ling explained, the same field moves the DNA too quickly, a classic scientific Catch-22.

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In this illustration, a DNA strand is leashed to a magnetized, iron-oxide bead, with a magnet hovering over it. As the bead moves toward the magnet, the DNA strand passes through nano-sized opening slowly enough that its base pairs can be read. Credit: Hongbo Peng/IBM Research.

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The trick is to figure out how to slow the strands' movement through the opening so the base pairs (A, T, C, and G) can be read. To solve that, Ling and Hongbo Peng, the lead author who performed the work as a graduate student at Brown and who now works at IBM, attached the DNA strand to a bead using a streptavidin-biotin bond. Like previous researchers, they used an electric field to drive the DNA strand toward the pore. But while the strand could pass through the pore, the bead, with a 2.8-micron diameter, was too large for the pore, which has a diameter of only 10 nanometres. So the bead was stuck in the hole with the attached DNA strand suspended on the other side of the membrane. The Brown researchers then used magnets — they call them "magnetic tweezers" — to draw the iron-oxide bead away from the pore. As the bead moves toward the magnets, the attached DNA strand moves through the pore — slowly enough so that the base pairs can be read. The scientists named their process "reverse DNA translocation" because, as Ling explained, "the DNA is essentially caught in a tug-of-war. And the speed of translocation will be controlled not solely by the electric field but by striking some balance between the magnetic and the electric fields. From there, we can tune it to dictate the speed." The scientists report their technique reduces the average speed of the DNA strand's passage by more than 2,000-fold. "It can be slower even. There is no limit," Ling said. A similar experiment has been done using optical tweezers, Ling said, but it involves only one DNA strand at a time. The Brown method sends multiple strands through the nanopores simultaneously. "It is scalable," Ling said. The researchers expect to test their technique in experiments using bacterial DNA. ......... ZenMaster

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A New Method for Bone-marrow-derived Liver Stem Cells Isolation

Researchers designed a culture system to isolate, proliferate and differentiate liver stem cells directly from bone marrow cells. Thursday, 16 April 2009 Great interest has been aroused in the identification and isolation of liver stem cells from bone marrow cells. Several subsets of bone marrow cells have been found to have the potential to differentiate into hepatocytes, however, sorting based on immunological methods is difficult because of the complicated surface markers of the stem cells; furthermore, no report of successful passage has been published. A research article to be published on April 7, 2009 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Yun-Feng Cai and his colleagues from the Affiliated Foshan Hospital and the Second Affiliated Hospital of Sun Yat-sen University established a carefully designed culture system to isolate, proliferate and differentiate liver stem cells directly from bone marrow cells, and they were able to achieve six passages of the stem cells. The results suggest that BDLSCs can be purified and passaged (proliferated). The selecting culture system that contains cholestatic serum can purify BDLSCs directly from bone marrow cells, which provides an easy method to separate stem cells, by avoiding complicated immunological manipulation. The successful passage of the stem cells further verifies the proliferating ability of the cells, although the passage is limited, and further research will provide more experience. In this study, the authors used their original method to retrieve the cells, which are possibly BDLSCs. Then, they used fluorescence-activated cell sorting to determine the cells' characteristics before and after differentiation. This is an interesting and potentially important study, which suggests that bone-marrow-derived cells can be stimulated to expand and then differentiate into hepatocyte-like cells, which can possibly be used to treat liver disease. Reference: Passage of bone marrow-derived liver stem cells with a proliferating culture system Yun-Feng Cai, Ji-Sheng Chen, Shu-Ying Su, Zuo-Jun Zhen, Huan-Wei Chen World J Gastroenterol 2009, 15(13): 1630-1635 ......... ZenMaster

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