Category Archives: Stem Cell Videos

Public release date: 29-Mar-2012 [ | E-mail | Share ]

Contact: Melissa Marino melissa.marino@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Vanderbilt-Ingram Cancer Center researchers have identified a new population of intestinal stem cells that may hold clues to the origin of colorectal cancer.

This new stem cell population, reported March 30 in the journal Cell, appears to be relatively quiescent (inactive) in contrast to the recent discovery of intestinal stem cells that multiply rapidly and is marked by a protein, Lrig1, that may act as a "brake" on cell growth and proliferation.

The researchers have also developed a new and clinically relevant mouse model of colorectal cancer that investigators can now use to better understand where and how the disease arises, as well as for probing new therapeutic targets.

Colorectal cancer is the second leading cause of cancer deaths in the United States. These tumors are thought to arise from a series of mutations in intestinal stem cells, which are long-lived, self-renewing cells that gives rise to all cell types in the intestinal tract.

For more than 30 years, scientists believed that intestinal stem cells were primarily quiescent, proliferating only rarely in order to protect the tissue against cancer. Then, in 2007, researchers reported finding a population of intestinal stem cells (marked by the molecule Lgr5) that were highly proliferative.

Those findings "really changed the way we think about intestinal stem cells," said Robert Coffey, Jr., M.D., Ingram Professor of Cancer Research, co-chair of Vanderbilt's Epithelial Biology Center and senior author on the study.

"It came to so dominate the field that it raised the question about whether quiescent stem cells even existand that's where we enter into the picture."

Coffey's lab studies the epidermal growth factor (EGF) signaling pathway which includes a family of receptors known as ErbBs and its role in cancers of epithelial tissues, like the intestinal tract.

Link:
Newly identified stem cells may hold clues to colon cancer

ROCKVILLE, Md., March 28, 2012 /PRNewswire/ --Neuralstem, Inc. (NYSE Amex: CUR) announced that safety results from the first 12 patients with amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) to receive its stem cells were reported online in the peer-reviewed publication, STEM CELLS, on March 13th. "Lumbar Intraspinal Injection of Neural Stem Cells in Patients with ALS: Results of a Phase I Trial in 12 Patients" (http://www.ncbi.nlm.nih.gov/pubmed/22415942.1) reports that one patient has shown improvement in his clinical status, even though researchers caution that the study was not designed to show efficacy. Additionally, there was no evidence of accelerated disease progression due to the intervention in any of the 12 patients, who were followed from 6-18 months after they were transplanted with the cells. All of the patients, who received transplants in the lumbar (lower back) region, tolerated the treatment without any long-term complications related to either the surgery or the cells.

(Logo: http://photos.prnewswire.com/prnh/20061221/DCTH007LOGO )

The 12 patients, part of the ongoing Phase I trial to evaluate the safety of Neuralstem's stem cells and transplantation procedure in patients with ALS, were the first in the world to receive intraspinal stem cell injections. Results from these patients were also were reported at the American Academy of Neurology Annual Meeting last September.

Based on a positive safety assessment, the trial has now been approved by the FDA to progress to transplanting ALS patients in the cervical (upper back) region of the spine, where the goal is to protect the motor neurons which affect respiratory function, and possibly prolong life. The fourteenth patient was transplanted earlier this month. All patients were treated at Emory University Hospital in Atlanta, Georgia.

"For these first 12 patients, we have met the objective of the Phase I trial, demonstrating safety for both the procedure of intraspinal injection and the presence of the neural stem cells in the spinal cords of ALS patients," said Jonathan Glass, MD, lead author of the publication. "We are encouraged by these results and have now advanced our trial to injections into the cervical spinal cord, targeting the motor neurons that control respiratory function." Dr. Glass is Professor of Neurology and Pathology at Emory University School of Medicine, as well as the Director of the Emory ALS Center.

"This important peer-reviewed publication reinforces our belief that we have demonstrated a safe, reproducible and robust route of administration into the spine for these spinal cord neural stem cells," said Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health System. "The publication covers data up to 18 months out from the original surgery. However, we must be cautious in interpreting this data, as this trial was neither designed nor statistically powered to study efficacy." Dr. Feldman is senior author on the study, principal investigator (PI) of the ALS trial and serves as a consultant to Neuralstem as part of her University of Michigan activities.

"As this article points out, our experience in the lumbar spinal cord has been overwhelmingly positive," commented Karl Johe, PhD, study author and Neuralstem Chairman and Chief Scientific Officer. "We have already transplanted two patients in the cervical spinal cord, where we believe we can affect patients' lives the most by improving their breathing. We are in active discussions with the FDA to increase the number of cells and the number of injections as well."

"We wish to thank the teams at Michigan and Emory for the tireless efforts required to refine this breakthrough method of administration of our neural stem cells. We'd also like to thank the patients and families involved in the trial," said Richard Garr, Neuralstem CEO and President. "The progress we have made to date is both substantial, and a true team effort."

About the Study

Safety results were reported on the first 12 patients in an ongoing Phase I study to evaluate the safety of Neuralstem's spinal cord stem cells (HSSC's), as well as the transplantation technique, in the treatment of ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

Read this article:
Neuralstem ALS Stem Cell Trial Interim Results Reported in the Journal, STEM CELLS

MIDDLETOWN

Wesleyan University researchers have reported some encouraging results about the potential for stem cells to treat a particularly debilitating form of epilepsy.

The research is the result of the collaboration of three labs at Wesleyan and focuses on temporal lobe epilepsy, which can be particularly difficult to treat, because many people who suffer from it don't respond to anti-seizure medications.

The condition usually begins with some kind of damage to the part of the brain known as the hippocampus, which then leads to the death of a particular neuron, the inhibitory interneuron.

"We started thinking about collaborating together to see if embryonic stem cells could be redirected to become the kinds of neurons that were dying," said Laura Grabel, professor of biology.

The first phase of the ongoing research resulted in a study published earlier this year in the Journal of Neuroscience.

Grabel and Janice Naegele, a developmental neurobiologist, worked together to develop a method of implanting embryonic stem cells of mice into the brains of mice. The mice were given a chemical to induce temporal lobe epilepsy.

"For the first time we could analyze the functions of these transplanted cells in the mice with the disease," Naegele said. "Are they responsible for preventing these seizures?"

To that end, the project was then turned over to Gloster Aaron, an assistant professor of neuroscience and behavior, who examined slices of the mice's brains under a microscope. The brain samples, kept in solution, can stay alive for eight to 12 hours. The results were promising.

"We found that these cells, derived from embryonic stem cells, could become functioning neurons in the brain," Grabel said. "Not only did they look like inhibitory interneurons, they behaved like them."

Excerpt from:
Wesleyan Research Suggests Stem Cells Show Promise Treating Epilepsy

A battle is heating up between a Republican-led state House panel and the University of Michigan over whether U-M must disclose its number of embryonic stem-cell lines.

It's the latest in a series of disagreements in recent months about everything from university funding to unionization of graduate student research assistants.

This time, Republicans on the subcommittee are upset with what they call U-M's "thumbing of their nose" at requests for information about embryonic stem cells. Several lawmakers said that if they don't get the information -- required under language passed in last year's budget -- they'll look at docking U-M's state aid.

U-M President Mary Sue Coleman said the university doesn't have an exact number of stem cells. She said it's important, instead, to place the work in the context of medical advances stem cells are leading.

Leonard Fleck, an ethics professor at Michigan State University's Center for Ethics and Humanities in the Life Sciences, said he doesn't believe lawmakers should legislate with the budget. He said that will be especially true as a better understanding of human genetics transforms medicine but runs afoul of some religious convictions.

Rep. Kevin Cotter, R-Mt. Pleasant, admitted the issue is about more than stem-cell research.

"It about the power of the Legislature to ask for reports. We're going to stand behind those requirements," he said.

Those involved in stem-cell research say a feud between Republican members of the state House higher education subcommittee and the University of Michigan is more about personal beliefs than state mandates.

The subcommittee is demanding to know the number of embryonic stem-cell lines and four related numbers at U-M. In a private meeting earlier this year, the chairman of the subcommittee told U-M officials they could lose state funding if they don't give those details.

U-M didn't give legislators the numbers, and now several committee members say they want to dock some of its state aid for flaunting the Legislature.

Follow this link:
Battle with GOP lawmakers over stem cells could cost U-M state aid

ScienceDaily (Mar. 26, 2012) A research network led by a Mayo Clinic physician found that stem cells derived from heart failure patients' own bone marrow and injected into their hearts improved the function of the left ventricle, the heart's pumping chamber. Researchers also found that certain types of the stem cells were associated with the largest improvement and warrant further study.

The results were presented March 26 at the 2012 American College of Cardiology Meeting in Chicago. They will also be published online in the Journal of the American Medical Association.

This Phase II clinical trial, designed to test this strategy to improve cardiac function, is an extension of earlier efforts in Brazil in which a smaller number of patients received fewer stem cells. For this new network study, 92 patients received a placebo or 100 million stem cells derived from the bone marrow in their hips in a one-time injection. This was the first study in humans to deliver that many bone marrow stem cells.

"We found that the bone marrow cells did not have a significant impact on the original end points that we chose, which involved reversibility of a lack of blood supply to the heart, the volume of the left ventricle of the heart at the end of a contraction, and maximal oxygen consumption derived through a treadmill test," says Robert Simari, M.D., a cardiologist at Mayo Clinic in Rochester, Minn. He is chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), the network of five academic centers and associated satellite sites that conducted the study. The CCTRN is supported by the National Heart, Lung, and Blood Institute, which also funded the study.

"But interestingly, we did find that the very simple measure of ejection fraction was improved in the group that received the cells compared to the placebo group by 2.7 percent," Dr. Simari says. Ejection fraction is the percentage of blood pumped out of the left ventricle during each contraction.

Study principal investigators Emerson Perin, M.D., Ph.D., and James Willerson, M.D., of the Texas Heart Institute, explain that even though 2.7 percent does not seem like a large number, it is statistically significant and means an improvement in heart function for chronic heart failure patients who have no other options.

"This was a pretty sick population," Dr. Perin says. "They had already had heart attacks, undergone bypass surgery, and had stents placed. However, they weren't at the level of needing a heart transplant yet. In some patients, particularly those who were younger or whose bone marrows were enriched in certain stem cell populations, had even greater improvements in their ejection fractions."

The average age of study participants was 63. The researchers found that patients younger than 62 improved more. Their ejection fraction improved by 4.7 percent. The researchers looked at the makeup of these patients' stem cells from a supply stored at a biorepository established by the CCTRN. They found these patients had more CD34+ and CD133+ type of stem cells in their mixture.

"This tells us that the approach we used to deliver the stems cells was safe," Dr. Simari says. "It also suggests new directions for the next series of clinical trials, including the type of patients, endpoints to study and types of cells to deliver."

Other co-authors of the study are Guilherme Silva, M.D., Deirdre Smith, Lynette Westbrook; and James Chen, all of the Texas Heart Institute, St. Luke's Episcopal Hospital, Houston; Carl Pepine, M.D., R. David Anderson, M.D., Christopher Cogle, M.D., and Eileen Handberg, Ph.D., all of the University of Florida School of Medicine, Gainesville; Timothy Henry, M.D., Jay Traverse, M.D., and Rachel Olson, all of the Minneapolis Heart Institute at Abbott Northwestern Hospital; Doris Taylor, Ph.D., and Claudia Zierold, Ph.D., both of the University of Minnesota School of Medicine, Minneapolis; Stephen Ellis, M.D., James Thomas, M.D., and Carrie Geither, all of The Cleveland Clinic Foundation, Ohio; David Zhao, M.D., Marvin Kornenberg, M.D., Antonis Hatzopoulos, Ph.D., Sherry Bowman, and Judy Francescon, all of Vanderbilt University School of Medicine, Tennessee; Dejian Lai, Ph.D., Sarah Baraniuk, Ph.D., Linda Piller, M.D., Lara Simpson, Ph.D., Judy Bettencourt, Shelly Sayre, Rachel Vojvodic, and Lemuel Moye, M.D., Ph.D., all of The University of Texas School of Public Health, Houston; A. Daniel Martin, Ph.D., of the University of Florida College of Public Health and Health Professions, Gainesville; Marc Penn, M.D., Ph.D., of Northeast Ohio Medical University, Akron; Saif Anwaruddin, M.D., of Penn Heart and Vascular Hospital of the University of Pennsylvania, Philadelphia; Adrian Gee, Ph.D., and David Aguilar, M.D., of Baylor College of Medicine, Houston; Catalin Loghin, M.D., of The University of Texas Medical School, Houston; and Sonia Skarlatos, Ph.D., David Gordon, M.D., Ph.D., Ray Ebert, Ph.D., and Minjung Kwak, Ph.D., all of the National Heart, Lung and Blood Institute, Bethesda, MD.

Here is the original post:
Bone marrow stem cells can improve heart function, study suggests

March 24, 2012

VIDEO ALERT: Audio and video resources are available on the Mayo Clinic News Blog.

EMBARGOED: Hold for release until Saturday, March 24, 2012, 8 a.m. CDT; American College of Cardiology

Newswise CHICAGO -- A research network led by a Mayo Clinic physician found that stem cells derived from heart failure patients own bone marrow and injected into their hearts improved the function of the left ventricle, the hearts pumping chamber. Researchers also found that certain types of the stem cells were associated with the largest improvement and warrant further study.

The results were presented today at the 2012 American College of Cardiology Meeting in Chicago. They will also be published online in the Journal of the American Medical Association.

This Phase II clinical trial, designed to test this strategy to improve cardiac function, is an extension of earlier efforts in Brazil in which a smaller number of patients received fewer stem cells. For this new network study, 92 patients received a placebo or 100 million stem cells derived from the bone marrow in their hips in a one-time injection. This was the first study in humans to deliver that many bone marrow stem cells.

We found that the bone marrow cells did not have a significant impact on the original end points that we chose, which involved reversibility of a lack of blood supply to the heart, the volume of the left ventricle of the heart at the end of a contraction, and maximal oxygen consumption derived through a treadmill test, says Robert Simari, M.D., a cardiologist at Mayo Clinic in Rochester, Minn. He is chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), the network of five academic centers and associated satellite sites that conducted the study. The CCTRN is supported by the National Heart, Lung, and Blood Institute, which also funded the study.

But interestingly, we did find that the very simple measure of ejection fraction was improved in the group that received the cells compared to the placebo group by 2.7 percent, Dr. Simari says. Ejection fraction is the percentage of blood pumped out of the left ventricle during each contraction.

Study principal investigators Emerson Perin, M.D., Ph.D., and James Willerson, M.D., of the Texas Heart Institute, explain that even though 2.7 percent does not seem like a large number, it is statistically significant and means an improvement in heart function for chronic heart failure patients who have no other options.

This was a pretty sick population, Dr. Perin says. They had already had heart attacks, undergone bypass surgery, and had stents placed. However, they werent at the level of needing a heart transplant yet. In some patients, particularly those who were younger or whose bone marrows were enriched in certain stem cell populations, had even greater improvements in their ejection fractions.

Go here to see the original:
Bone Marrow Stem Cells Improve Heart Function, Study Finds

By Prue Salasky

3:48 p.m. EDT, March 23, 2012

UVA recently performed the first two stem cell transplants in Virginia, using non-embryonic stem cells from umbilical cord blood. The Stem Cell Transplant Program offers both bone marrow and stem cell transplants, with a focus on cord blood, to treat leukemia, lymphoma, Hodkin's disease and other blood diseases.

The outcome isn't known yet, but in both patients the stem cells began producing new cells 14 days after the transplant instead of the 24 to 28 days it usually takes.

The cord blood comes from placentas that otherwise would be discarded following childbirth; its benefits include sidestepping ethical issues of embryonic stem cells; they're easier and faster to collect than stem cells from other sources; and they are immune tolerant (this means that they won't attack other cells in the body and match doesn't have to be exact).

Speed is important because there is a narrow window of opportunity to perform a transplant when a patient's disease is in remission.

The program is led by Mary Laughlin, who heads up a team of 29, including 4 other transplant physicians who started seeing patients in September. The program had anticipated doing 15 transplants in first year; now expects to do 100.

Read more:
Health Notes: UVA performs first stem cell transplants in Virginia

Published on Mar 25, 2012

(KOREA HERALD/ASIA NEWS NETWORK) - A joint research team from South Korea and Germany said on Friday they have created stem cells that have the potential to help treat people suffering from dementia and spinal cord trauma.

Scientists from Konkuk University and the Max Planck Institute said they have successfully used somatic cells from mice to create so-called induced neural stem cells (iNSCs) that can be cultivated for over a year under laboratory conditions.

The iNSCs have also been injected into the brains of mice and differentiated into various nerve cells without growing into malignant tumors.

'The discovery marks the first time ordinary somatic cells have been artificially engineered to become adult stem cells,' said Prof Han Dong Wook, a professor of stem cell biology at Konkuk, who led the research.

Follow this link:
Scientists develop stem cells that may help treat dementia

Shortly after a mouse embryo starts to form, some of its stem cells undergo a dramatic metabolic shift to enter the next stage of development, Seattle researchers report today. These stem cells start using and producing energy like cancer cells.

Julie Mathieu

A colony of human embryonic stem cells.

This discovery is published today in EMBO, the European Molecular Biology Organization journal.

These findings not only have implications for stem cell research and the study of how embryos grow and take shape, but also for cancer therapy, said the senior author of the study, Dr. Hannele Ruohola-Baker, University of Washington professor of biochemistry. The study was collaborative among several research labs in Seattle.

The metabolic transition they discovered occurs very early as the mouse embryo, barely more than a speck of dividing cells, implants in the mothers uterus. The change is driven by low oxygen conditions, Ruohola-Baker explained.

The researchers also saw a specific type of biochemical slowdown in the stem cells mitochondria the cells powerhouses. The phenomenon previously was associated with aging and disease. This was the first example of the same downshift controlling normal early embryonic development.

This downshift coincides with the time when the germ line, the keeper of the genome for the next generation, is set aside, Ruohola-Baker said.. Hence reduction of mitochondrial reactive oxygen species may be natures way to protect the future.

Embryonic stem cells are called pluripotent because they have the ability to renew themselves and have the potential to become any cell in the body. Self-sustaining and versatile are qualities necessary for the growth, repair and maintenance of the body and for regenerative medicine therapies.

Although they share these sought-after qualities, Pluripotent stem cells come in several flavors, Ruohola-Baker explained. They differ in subtle ways that expand or shrink their capacities as the raw living material from which animals are shaped.

More:
Embryonic stem cells shift metabolism in a cancer-like way upon implanting in the uterus

This discovery is published today in EMBO, the European Molecular Biology Organization journal.

"These findings not only have implications for stem cell research and the study of how embryos grow and take shape, but also for cancer therapy," said the senior author of the study, Dr. Hannele Ruohola-Baker, University of Washington professor of biochemistry. The study was collaborative among several research labs in Seattle.

The metabolic transition they discovered occurs very early as the mouse embryo, barely more than a speck of dividing cells, implants in the mother's uterus. The change is driven by low oxygen conditions, Ruohola-Baker explained.

The researchers also saw a specific type of biochemical slowdown in the stem cells' mitochondria the cells' powerhouses. The phenomenon previously was associated with aging and disease. This was the first example of the same downshift controlling normal early embryonic development.

"This downshift coincides with the time when the germ line, the keeper of the genome for the next generation, is set aside," Ruohola-Baker said.. "Hence reduction of mitochondrial reactive oxygen species may be nature's way to protect the future."

Embryonic stem cells are called pluripotent because they have the ability to renew themselves and have the potential to become any cell in the body. Self-sustaining and versatile are qualities necessary for the growth, repair and maintenance of the body and for regenerative medicine therapies.

Although they share these sought-after qualities, "Pluripotent stem cells come in several flavors," Ruohola-Baker explained. They differ in subtle ways that expand or shrink their capacities as the raw living material from which animals are shaped.

There's a big reason why the researchers wanted to understand the distinction between the stem cells that make up the inner cell mass of the free-floating mouse embryo, and those in the epiblast, or implantation stage. Mouse embryonic cells at the epiblast stage more closely resemble human embryonic stem cells -- and cancer cells.

Human stem cells and mouse epiblast stem cells have lower mitochondrial respiration activity than do earlier stage mouse stem cells. This reduction occurs despite the fact that the later stage stem cells have more mature mitochondria. The researchers confirmed that certain genes that control mitochondria are turned down during the transition from inner cells mass to epiblast cells.

Instead, the transitioning cells obtain their energy exclusively from breaking down a sugar, glucose. In contrast, the earlier stage mouse embryonic stem cells have more energy options, dynamically switching from mitochondrial respiration to glucose breakdown on demand.

Read this article:
Embryonic stem cells shift metabolism in cancer-like way upon implanting in uterus