PUBLIC RELEASE DATE:

7-Jan-2014

Contact: Jeffrey Norris jeffrey.norris@ucsf.edu 415-502-6397 University of California - San Francisco

Researchers have developed a new way to study bone disorders and bone growth, using stem cells from patients afflicted with a rare, genetic bone disease. The approach, based on Nobel-Prize winning techniques, could illuminate the illness, in which muscles and tendons progressively turn into bone, and addresses the similar destructive process that afflicts a growing number of veterans who have suffered blast injuries including traumatic amputations or injuries to the brain and nervous system. This insidious hardening of tissues also grips some patients following joint replacement or severe bone injuries.

The disease model, described in a new study by a UC San Francisco-led team, involves taking skin cells from patients with the bone disease, reprogramming them in a lab dish to their embryonic state, and deriving stem cells from them.

Once the team derived the stem cells, they identified a cellular mechanism that drives abnormal bone growth in the thus-far untreatable bone disease, called fibrodysplasia ossificans progressiva (FOP). Furthermore, they found that certain chemicals could slow abnormal bone growth in the stem cells, a discovery that might help guide future drug development.

Clinically, the genetic and trauma-caused conditions are very similar, with bone formation in muscle leading to pain and restricted movement, according to the leader of the new study, Edward Hsiao, MD, PhD, an endocrinologist who cares for patients with rare and unusual bone diseases at the UCSF Metabolic Bone Clinic in the Division of Endocrinology and Metabolism.

The human cell-based disease model is expected to lead to a better understanding of these disorders and other illnesses, Hsiao said.

"The new FOP model already has shed light on the disease process in FOP by showing that the mutated gene can affect different steps of bone formation," Hsiao said. "These different stages represent potential targets for limiting or stopping the progression of the disease, and may also be useful for blocking abnormal bone formation in other conditions besides FOP. The human stem-cell lines we developed will be useful for identifying drugs that target the bone-formation process in humans," Hsiao said.

The team's development of, and experimentation with, the human stem-cell disease model for FOP, published in the December issue of the Orphanet Journal of Rare Diseases, is a realization of the promise of research using stem cells of the type known as induced pluripotent stem (iPS) cells, immortal cells of nearly limitless potential, derived not from embryos, but from adult tissues.

Excerpt from:
Stem cells used to model disease that causes abnormal bone growth

Jan. 7, 2014 Scientists at the University of Copenhagen have gained new insight into how both early embryonic cells and embryonic stem cells are directed into becoming specialized cell types, like pancreatic and liver cells. The results have just been published in the scientific journal eLife.

This latest research from the Danish Stem Cell Center (Danstem) at the University of Copenhagen, helps identify how stem cells create so called pathways and roads supporting their own specialization. This understanding is an important step towards stem cell-based cell therapies for conditions like diabetes and liver diseases.

"The new insight that we have gained into the impact of the physical environment on cell development is highly valuable," says Professor Joshua Brickman from DanStem, "It enables us to create the optimal physical environment in the laboratory for stem cells and progenitor cells to develop into specific, mature cells."

Developing cells constantly move and while moving around, they organize and build a physical environment very much like a small city with pathways and roads. The new research published in the scientific journal eLife shows two important things. Firstly the embryonic cells receive signals from other cells that actually instruct them in how to organize and build the road leading the cells towards early stages of pancreas and liver cells.

Professor Brickman and his team also found that they could isolate these roads from the developing stem cells and literally freeze them. The saved roads were then used in a separate experiment which showed that in the absence of an important cell signal, the road alone can be used to improve the cells' development and differentiation towards mature cells.

"Apart from gaining new important insight into cell development, our work also suggests that some of the current approaches to human embryonic stem cells specialization towards both pancreatic and liver cells may not have been effective, because the important role of these roads, the so called extra-cellular matrix, was ignored," says Joshua Brickman.

Originally posted here:
Stem cells on road to specialization

PUBLIC RELEASE DATE:

7-Jan-2014

Contact: Joshua Brickmann joshua.brickman@sund.ku.dk 45-51-68-04-38 University of Copenhagen

Scientists at the University of Copenhagen have gained new insight into how both early embryonic cells and embryonic stem cells are directed into becoming specialised cell types, like pancreatic and liver cells. The results have just been published in the scientific journal eLife.

This latest research from the Danish Stem Cell Center (Danstem) at the University of Copenhagen, helps identify how stem cells create so called pathways and roads supporting their own specialisation. This understanding is an important step towards stem cell-based cell therapies for conditions like diabetes and liver diseases.

"The new insight that we have gained into the impact of the physical environment on cell development is highly valuable," says Professor Joshua Brickman from DanStem, "It enables us to create the optimal physical environment in the laboratory for stem cells and progenitor cells to develop into specific, mature cells."

On the road

Developing cells constantly move and while moving around, they organise and build a physical environment very much like a small city with pathways and roads. The new research published in the scientific journal eLife shows two important things. Firstly the embryonic cells receive signals from other cells that actually instruct them in how to organise and build the road leading the cells towards early stages of pancreas and liver cells.

Professor Brickman and his team also found that they could isolate these roads from the developing stem cells and literally freeze them. The saved roads were then used in a separate experiment which showed that in the absence of an important cell signal, the road alone can be used to improve the cells' development and differentiation towards mature cells.

"Apart from gaining new important insight into cell development, our work also suggests that some of the current approaches to human embryonic stem cells specialisation towards both pancreatic and liver cells may not have been effective, because the important role of these roads, the so called extra-cellular matrix, was ignored," says Joshua Brickman.

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Stem cells on the road to specialization

PUBLIC RELEASE DATE:

7-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 7, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute, working in collaboration with scientists from Columbia University Medical Center (CUMC), for the first time generated induced pluripotent stem (iPS) cells lines from non-cryoprotected brain tissue of patients with Alzheimer's disease.

These new stem cell lines will allow researchers to "turn back the clock" and observe how Alzheimer's develops in the brain, potentially revealing the onset of the disease at a cellular level long before any symptoms associated with Alzheimer's are displayed. These reconstituted Alzheimer's cells will also provide a platform for drug testing on cells from patients that were definitively diagnosed with the disease. Until now, the only available method to definitively diagnose Alzheimer's disease that has been available to researchers is examining the brain of deceased patients. This discovery will permit scientists for the first time to compare "live" brain cells from Alzheimer's patients to the brain cells of other non-Alzheimer's patients.

NYSCF scientists successfully produced the iPS cells from frozen tissue samples stored for up to eleven years at the New York Brain Bank at Columbia University.

This advance, published today in Acta Neuropathologica Communications , shows that disease-specific iPS cells can be generated from readily available biobanked tissue that has not been cryoprotected, even after they have been frozen for many years. This allows for the generation of iPS cells from brains with confirmed disease pathology as well as allows access to rare patient variants that have been banked. In addition, findings made using iPS cellular models can be cross-validated in the original brain tissue used to generate the cells. The stem cell lines generated for this study included samples from patients with confirmed Alzheimer's disease and four other neurodegenerative diseases.

This important advance opens up critical new avenues of research to study cells affected by disease from patients with definitive diagnoses. This success will leverage existing biobanks to support research in a powerful new way.

iPS cells are typically generated from a skin or blood sample of a patient by turning back the clock of adult cells into pluripotent stem cells, cells that can become any cell type in the body. While valuable, iPS cells are often generated from patients without a clear diagnosis of disease and many neurodegenerative diseases, such as Alzheimer's disease, often lack specific and robust disease classification and severity grading. These diseases and their extent can only be definitively diagnosed by post-mortem brain examinations. For the first time we will now be able to compare cells from living people to cells of patients with definitive diagnoses generated from their banked brain tissue.

Brain bank networks, which combined contain tens of thousands of samples, provide a large and immediate source of tissue including rare disease samples and a conclusive spectrum of disease severity among samples. The challenge to this approach is that the majority of biobanked brain tissue was not meant for growing live cells, and thus was not frozen in the presence of cryoprotectants normally used to protect cells while frozen. NYSCF scientists in collaboration with CUMC scientists have shown that these thousands of samples can now be used to make living human cells for use in disease studies and to develop new drugs or preventative treatments for future patients.

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NYSCF scientists make living brain cells from Alzheimer's patients biobanked brain tissue