Tag Archive for 'Harvard Medical School'

Brain stem cell transplant may pave way for Parkinson’s

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Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed.

Collaborators from Harvard University, Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain.

Repair at the cellular-level of the hypothalamus — a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression — indicates the possibility of new therapeutic approaches to even higher-level conditions such as spinal cord injury, autism, epilepsy, ALS  (Lou Gehrig’s disease), Parkinson’s disease, and Huntington’s disease.

In 2005, Harvard Medical School Dean Jeffrey Flier, then the George C. Reisman professor of medicine at BIDMC, published a landmark study showing that an experimental drug spurred the addition of new neurons in the hypothalamus and offered a potential treatment for obesity. File photo by Stephanie Mitchell/Harvard Staff Photographer

“There are only two areas of the brain that are known to normally undergo ongoing large-scale neuronal replacement during adulthood on a cellular level — so-called ‘neurogenesis,’ or the birth of new neurons — the olfactory bulb and the subregion of the hippocampus called the dentate gyrus, with emerging evidence of lower level ongoing neurogenesis in the hypothalamus,” said Jeffrey Macklis, Harvard University professor of stem cell and regenerative biology and HMS professor of neurology at MGH, and one of three corresponding authors on the paper. “The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling.  Here we’ve rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function.”

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SANUWAVE’S PACE Shows Promise In Stimulating Autogenous Sources Of Progenitor/STEM Cells For Harvest And Re-Transplantation In Bone Tissue Engineering

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SANUWAVE Inc., an emerging medical technology company focused on the development and commercialization of non-invasive, biological response activating devices in the regenerative medicine area, reported that scientific findings titled “Extracorporeal Shock Wave Stimulation of Osteoprogenitor Cells” were presented at the 2009 International Bone-Tissue-Engineering Congress (“Bone-Tec”) in Hannover, Germany, which was held October 9-11, 2009.

Dr. Myron Spector, PhD, Professor of Orthopaedic Surgery (Biomaterials) at Harvard Medical School, Director of Orthopaedic Research at Brigham and Women’s Hospital and Director of Tissue Engineering at VA Boston Healthcare System, was an invited guest speaker at the Conference. The Bone–Tec Congress featured an international scientific forum to discuss progresses in modern bone tissue regeneration and extended a worldwide network to exchange findings on the latest developments.

Dr. Spector’s team employed SANUWAVE’s Pulsed Acoustic Cellular Expression (PACE™) technology in preclinical research to create autogenous sources of stem cells for bone tissue engineering. Results support the proposition that PACE™ could be employed as a non-invasive technique to cause proliferation and thickening of the cambium layer of the femur’s periosteum for the subsequent intraoperative harvesting of progenitor stem cells days later for bone or cartilage regeneration.

PACE™ stimulated a dramatic proliferation and thickening (up to 10 fold) of osteoprogenitor stem cells, precursors to bone and cartilage cells, in the cambium layer of the periosteum in the femur of the adult rats within 4 days. Neovascularization and new bone formation within the thickened periosteum were also evident after 4 days.

Dr. Spector said, “This research has shown great potential. Through more study, this technology could further advance tissue engineering autologous transplant techniques towards clinical applications such as bone reconstruction and cartilage defect repair.” (…)

from http://www.sanuwave.com

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Diabetes Medication May Get New Life as Cancer Treatment

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The drug metformin, a mainstay of diabetes care for 15 years, may have a new life as a cancer treatment, researchers said.
In a study in mice, low doses of the drug, combined with a widely used chemotherapy called doxorubicin, shrank breast-cancer tumors and prevented their recurrence more effectively than chemotherapy alone.

The findings add to a growing body of evidence that metformin, marketed as Glugophase by Bristol-Myers Squibb Co. and available in generic versions, could be a potent antitumor medicine.
They also lend support to an emerging theory that cancer’s ability to survive and resist therapy is regulated by cancer stem cells that drive a tumor’s growth and survival.

Chemotherapy is effective against many tumors, said Kevin Struhl, a Harvard Medical School researcher and principal investigator of the study. “The problem is cancer stem cells acquire resistance” to treatment, he said. “They are able to regenerate the tumor and as a result you end up with a relapse.”
About 5% to 10% of a tumor’s cells are believed to be cancer stem cells, he said.

In the report, being published in the Oct. 1 edition of Cancer Research, a journal of the American Association for Cancer Research, researchers said the combination of metformin and doxorubicin killed both regular cancer cells and cancer stem cells.
In contrast, doxorubicin alone had limited effect on the stem cells.

(…)

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New Hope For Kidney Disease Patients from Stem Cells

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Several cell-based therapy approaches could provide new treatments for patients with Alport syndrome, reports an upcoming paper in the Journal of the American Society of Nephrology.

“Our study opens up many considerations of how new therapies related to the use of stem cells can be devised for our kidney patients with chronic disease,” comments Raghu Kalluri, MD, PhD (Harvard Medical School, Boston, MA) (…)

The experiments provide evidence that stem cell treatments could repair the kidney defects associated with Alport syndrome. “We found that stem cells derived from adult bone marrow are equally useful as embryonic stem cells,” says Kalluri. “This will make it easier to translate these scientific discoveries to a treatment protocol for patients with Alport syndrome.” (…)

from http://www.sciencedaily.com/releases/2009/10/091015171451.htm

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Maryland in the biotechnology spotlight: Cancer stem cell research gains traction, tackles new targets

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In the decades-long war on cancer, as of late, researchers had been making little progress in comparison to colleagues treating other conditions, such as cardiac or infectious diseases. “Cancer research has really plateaued out,” William Matsui, an associate professor of oncology at Johns Hopkins University‘s School of Medicine, said at the 2009 World Stem Cell Summit here on Tuesday. But pushing cancer stem cell research “gives us a novel way to study cancer,” said Matsui, who also runs a lab at the university’s Sidney Kimmel Comprehensive Cancer Center.

Cancer and stem cells have had a fraught relationship—not in the least because of early concern that stem cell treatments could in fact spur on cancer through their encouragement of undifferentiated cell growth. But cancer stem cells themselves have gained a more solid toe-hold in the past several years as a potential new target for cancer research.

Cancer stem cells—or CSCs—are presumed to have similar capabilities as healthy stem cells: they can regenerate and differentiate into any cell that makes up the cancer. Such cells are often blamed for relapses in patients who by all other measures appear to have been cured. One of the large problems, however, has been in finding these cells. In some cancers, such as some leukemias, they are suspected to be only one cell in a million.

Cancer stem cells’ persistence has given rise to the so-called dandelion theory of cancer treatment. Researchers and doctors have traditionally worked to obliterate the visible cancerous menace—the tumor, or dandelion weed, as it were. But as anyone with a lawn may be well aware, hacking off the flower does little to stop the root—that is, the stem cell—from regenerating another attack later. So, posits Richard Jones, also at the Sidney Kimmel Comparative Cancer Center, it’s possible that effective drugs may have been abandoned because they were not creating quick, visible responses. Eliminating the root stem cells will cause the tumors to stop growing, but not right away, he explained at the summit.

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Stem Cells Used to Grow Hearts

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From left to right: A normal pig heart, a pig heart after being decellularised, the pig heart prepared for recellularisation. Photos courtesy of the University of Minnesota.

In a medical first, University researchers have created a beating heart in the laboratory. Using detergents, they stripped away the cells from rat hearts until only the nonliving matrix, or “skeleton,” was left; they then repopulated the matrix with fresh heart cells.

If perfected, the technique may be used someday to generate new hearts for patients. In the United States alone, about 5 million people live with heart failure, 550,000 new cases are diagnosed every year, and 50,000 die waiting for a donor heart.

“The results were a home run,” says Doris Taylor, director of the University’s Center for Cardiovascular Repair and a principal investigator on the study. “We knew that cell therapy–that is, transplanting cells into [a patient's damaged] heart–is not a panacea. So we started thinking, ‘Is there a way to use cells to engineer heart tissue?’”

The idea, she says, is to create whole new blood vessels or organs by implanting a patient’s own cells into a matrix derived from a donor organ. This approach ought to bypass the problem of organ rejection because the matrix, being devoid of cells, shouldn’t provoke an immune response. Even if it did, the new cells would create a fresh matrix of their own, which would turn off the immune response and free patients from the need to take immunosuppressive drugs.

The process, called whole organ recellularization, can be done “with virtually any organ,” Taylor says.

A simple plan

The main hurdle in creating new hearts wasn’t finding the right cells but recreating the vastly complex architecture of the heart, Taylor explains. In puzzling it over, she and Harald Ott, a research associate in the center (now a surgical resident at Harvard Medical School and first author of the study), hit on a way to get nature to solve the problem for them.

To remove cells from fresh rat hearts, the researchers pumped solutions of detergents through the network of blood vessels that normally nourish the organ. The treatment popped all the cells like balloons and washed away the debris, leaving the matrix of protein fibers that form the backbone of a living heart’s connective tissue. It’s called the extracellular matrix, or ECM.

http://brightcove.vo.llnwd.net/d7/unsecured/media/981571807/981571807_25285320001_rat-heart-.flv

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