PUBLIC RELEASE DATE:

9-Jan-2014

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

Putnam Valley, NY. (Jan. 9, 2014) Using skin-derived stem cells (SDSCs) and a previously developed collagen tube designed to successfully bridge gaps in injured nerves in rat models, the research team in Milan, Italy that established and tested the procedure has successfully rescued peripheral nerves in the upper arms of a patient suffering peripheral nerve damage who would have otherwise had to undergo amputations.

The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1096.

"Peripheral nerve repair with satisfactory functional recovery remains a great surgical challenge, especially for severe nerve injuries resulting in extended nerve defects," said study corresponding author Dr. Yvan Torrente, of the Department of Pathophysiology and Transplantation at the University of Milan. "However, we hypothesized that the combination of autologous (self-donated) SDSCs placed in collagen tubes to bridge gaps in the damaged nerves would restore the continuity of injured nerves and save from amputation the upper arms of a patient with poly-injury to motor and sensory nerves."

Although autologous nerve grafting has been the 'gold standard' for reconstructive surgeries, these researchers felt that there were several drawbacks to that approach, including graft availability, donor site morbidity, and neuropathic pain.

According to the researchers, autologous SDSCs have advantages over other stem cells as they are an accessible source of stem cells rapidly expandable in culture, and capable of survival and integration within host tissues.

While the technique of using the collagen tubes - NeuraGen, an FDA-approved device - to guide the transplanted cells over gaps in the injured nerve had been previously developed and tested by the same researchers with the original research successfully saving damaged sciatic nerves on rats, the present case, utilizing the procedure they developed employing SDSCs and a nerve guide, is the first to be carried out on a human.

Over three years, the researchers followed up on the patient, assessing functional recovery of injured median and ulnar nerves by pinch gauge test and static two-point discrimination and touch test with monofiliments along with electrophysiological and MRI examinations.

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Stem cells injected into nerve guide tubes repair injured peripheral nerve

3 hours ago This is Harvard Associate Professor Jeffrey Karp, Ph.D. (left), and James Ankrum, Ph.D. (right). Credit: Brigham and Women's Hospital

Harvard stem cells scientists at Brigham and Women's Hospital and MIT can now engineer cells that are more easily controlled following transplantation, potentially making cell therapies, hundreds of which are currently in clinical trials across the United States, more functional and efficient.

Associate Professor Jeffrey Karp, PhD, and James Ankrum, PhD, demonstrate in this month's issue of Nature Protocols how to load cells with microparticles that provide the cells cues for how they should behave over the course of days or weeks as the particles degrade.

"Regardless of where the cell is in the body, it's going to be receiving its cues from the inside," said Karp, a Harvard Stem Cell Institute Principal Faculty member at Brigham and Women's Hospital. "This is a completely different strategy than the current method of placing cells onto drug-doped microcarriers or scaffolds, which is limiting because the cells need to remain in close proximity to those materials in order to function. Also these types of materials are too large to be infused into the bloodstream."

Cells are relatively simple to control in a Petri dish. The right molecules or drugs, if internalized by a cell, can change its behavior; such as inducing a stem cell to differentiate or correcting a defect in a cancer cell. This level of control is lost after transplantation as cells typically behave according to environmental cues in the recipient's body. Karp's strategy, dubbed particle engineering, corrects this problem by turning cells into pre-programmable units. The internalized particles stably remain inside the transplanted cell and tell it exactly how to act, whether the cell is needed to release anti-inflammatory factors or regenerate lost tissue.

"Once those particles are internalized into the cells, which can take on the order of 6-24 hours, we can deliver the transplant immediately or even cryopreserve the cells," Karp said. "When the cells are thawed at the patient's bedside, they can be administered and the agents will start to be released inside the cells to control differentiation, immune modulation or matrix production, for example."

It could take more than a decade for this type of cell therapy to be a common medical practice, but to speed up the pace of research, Karp published the Nature Protocols study to encourage others in the scientific community to apply the technique to their fields. The paper shows the range of different cell types that can be particle engineered, including stem cells, immune cells, and pancreatic cells.

"With this versatile platform, which leveraged Harvard and MIT experts in drug delivery, cell engineering, and biology, we've demonstrated the ability to track cells in the body, control stem cell differentiation, and even change the way cells interact with immune cells," said Ankrum, a former graduate student in Karp's laboratory. "We're excited to see what applications other researchers will imagine using this platform."

Explore further: Stem cells engineered to become targeted drug factories

More information: Engineering cells with intracellular agent-loaded microparticles to control cell phenotype. Nature Protocols. January 9, 2014 [Epub ahead of print]

Read more here:
Scientists control cells following transplantation, from the inside out

Posted: Thursday, January 9, 2014, 9:00 AM

THURSDAY, Jan. 9, 2014 (HealthDay News) -- A patient's own bone marrow stem cells might someday be used to treat multidrug-resistant tuberculosis, a new study suggests.

The phase 1 study to assess the safety of the treatment included 30 patients, aged 21 to 65, with multidrug-resistant tuberculosis or the even more dangerous extensively drug-resistant tuberculosis. They received standard tuberculosis antibiotic treatment and an infusion of about 10 million of their own bone marrow stem cells.

A comparison group of 30 patients with either type of tuberculosis received standard treatment only.

After 18 months, 16 patients treated with bone marrow stem cells were cured, compared with five patients in the standard group, the study authors said. The most common side effects in the stem cell group were high cholesterol (14 patients), nausea (11), and lymphopenia (low white blood cell count) or diarrhea (10).

There were no serious side effects, according to the study, which was published Jan. 8 in The Lancet Respiratory Medicine.

Conventional treatment for multidrug-resistant tuberculosis uses a combination of antibiotics that can cause harmful side effects in patients, study leader Markus Maeurer, a professor at Karolinska University Hospital in Sweden, said in a journal news release.

"Our new approach, using the patients' own bone marrow stromal cells, is safe and could help overcome the body's excessive inflammatory response, repair and regenerate inflammation-induced damage to lung tissue, and lead to improved cure rates," Maeurer said in the news release.

Longer follow-up with more patients is needed to confirm the safety and effectiveness of the stem cell therapy, he said.

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Could Stem Cells Cure Drug-Resistant Tuberculosis?

Jan. 9, 2014 A fast and comprehensive method for determining the function of genes could greatly improve our understanding of a wide range of diseases and conditions, such as heart disease, liver disease and cancer.

The method uses stem cells with a single set of chromosomes, instead of the two sets found in most cells, to reveal what causes the "circuitry" of stem cells to be rewired as they begin the process of conversion into other cell types. The same method could also be used to understand a range of biological processes.

Embryonic stem cells rely on a particular gene circuitry to retain their original, undifferentiated state, making them self-renewing. The dismantling of this circuitry is what allows stem cells to start converting into other types of cells -- a process known as cell differentiation -- but how this happens is poorly understood.

Researchers from the University of Cambridge Wellcome Trust-MRC Stem Cell Institute have developed a technique which can pinpoint the factors which drive cell differentiation, including many that were previously unidentified. The method, outlined in the Thursday (9 January) edition of the journal Cell Stem Cell, uses stem cells with a single set of chromosomes to uncover how cell differentiation works.

Cells in mammals contain two sets of chromosomes -- one set inherited from the mother and one from the father. This can present a challenge when studying the function of genes, however: as each cell contains two copies of each gene, determining the link between a genetic change and its physical effect, or phenotype, is immensely complex.

"The conventional approach is to work gene by gene, and in the past people would have spent most of their careers looking at one mutation or one gene," said Dr Martin Leeb, who led the research, in collaboration with Professor Austin Smith. "Today, the process is a bit faster, but it's still a methodical gene by gene approach because when you have an organism with two sets of chromosomes that's really the only way you can go."

Dr Leeb used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells. These haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential, making them a powerful tool for determining how the genetic circuitry of mammalian development functions.

The researchers used transposons -- "jumping genes"- to make mutations in nearly all genes. The effect of a mutation can be seen immediately in haploid cells because there is no second gene copy. Additionally, since embryonic stem cells can convert into almost any cell type, the haploid stem cells can be used to investigate any number of conditions in any number of cell types. Mutations with important biological effects can then rapidly be traced to individual genes by next generation DNA sequencing.

"This is a powerful and revolutionary new tool for discovering how gene circuits operate," said Dr Leeb. "The cells and the methodology we've developed could be applied to a huge range of biological questions."

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Rewiring stem cells: New technique may revolutionize understanding of how genes function

LONDON - Patients with potentially fatal "superbug" forms of tuberculosis (TB) could in future be treated using stem cells taken from their own bone marrow, according to the results of an early-stage trial of the technique.

The finding, made by British and Swedish scientists, could pave the way for the development of a new treatment for the estimated 450,000 people worldwide who have multi drug-resistant (MDR) or extensively drug-resistant (XDR) TB.

In a study in The Lancet Respiratory Medicine journal on Thursday, researchers said more than half of 30 drug-resistant TB patients treated with a transfusion of their own bone marrow stem cells were cured of the disease after six months.

"The results ... show that the current challenges and difficulties of treating MDR-TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily," said TB expert Alimuddin Zumla at University College London, who co-led the study.

TB, which infects the lungs and can spread from one person to another through coughing and sneezing, is often falsely thought of as a disease of the past.

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Bone marrow stem cells could defeat drug-resistant TB, trial study finds

2 hours ago This is a set of chromosomes in haploid mouse embryonic stem cells. Credit: Martin Leeb

A fast and comprehensive method for determining the function of genes could greatly improve our understanding of a wide range of diseases and conditions, such as heart disease, liver disease and cancer.

The method uses stem cells with a single set of chromosomes, instead of the two sets found in most cells, to reveal what causes the "circuitry" of stem cells to be rewired as they begin the process of conversion into other cell types. The same method could also be used to understand a range of biological processes.

Embryonic stem cells rely on a particular gene circuitry to retain their original, undifferentiated state, making them self-renewing. The dismantling of this circuitry is what allows stem cells to start converting into other types of cells - a process known as cell differentiation - but how this happens is poorly understood.

Researchers from the University of Cambridge Wellcome Trust-MRC Stem Cell Institute have developed a technique which can pinpoint the factors which drive cell differentiation, including many that were previously unidentified. The method, outlined in the Thursday (9 January) edition of the journal Cell Stem Cell, uses stem cells with a single set of chromosomes to uncover how cell differentiation works.

Cells in mammals contain two sets of chromosomes one set inherited from the mother and one from the father. This can present a challenge when studying the function of genes, however: as each cell contains two copies of each gene, determining the link between a genetic change and its physical effect, or phenotype, is immensely complex.

"The conventional approach is to work gene by gene, and in the past people would have spent most of their careers looking at one mutation or one gene," said Dr Martin Leeb, who led the research, in collaboration with Professor Austin Smith. "Today, the process is a bit faster, but it's still a methodical gene by gene approach because when you have an organism with two sets of chromosomes that's really the only way you can go."

Dr Leeb used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells. These haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential, making them a powerful tool for determining how the genetic circuitry of mammalian development functions.

The researchers used transposons "jumping genes" to make mutations in nearly all genes. The effect of a mutation can be seen immediately in haploid cells because there is no second gene copy. Additionally, since embryonic stem cells can convert into almost any cell type, the haploid stem cells can be used to investigate any number of conditions in any number of cell types. Mutations with important biological effects can then rapidly be traced to individual genes by next generation DNA sequencing.

"This is a powerful and revolutionary new tool for discovering how gene circuits operate," said Dr Leeb. "The cells and the methodology we've developed could be applied to a huge range of biological questions."

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Rewiring stem cells