(Press-News.org) Contact information: Jeffrey Norris
jeffrey.norris@ucsf.edu
415-502-6397
University of California - San Francisco
Stem cells used to model disease that causes abnormal bone growth
UCSF-led study sheds light on muscle-to-bone transformation
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.
Shinya Yamanaka, MD, PhD, a UCSF professor of anatomy and a senior investigator with the UCSF-affiliated Gladstone Institutes, as well as the director of the Center for iPS Cell Research and Application (CiRA) and a principal investigator at Kyoto University, shared the Nobel Prize in 2012 for discovering how to make iPS cells from skin cells using a handful of protein "factors." These factors guide a reprogramming process that reverts the cells to an embryonic state, in which they have the potential to become virtually any type of cell.
Because injuries and surgeries can trigger rapid bone formation in FOP patients, obtaining tissue samples for extensive lab study is extremely difficult. Human iPS cells provide a unique solution by allowing the creation of the needed tissues in the lab. Hsiao and colleagues carefully gathered skin samples from donors, and then grew the skin cells in culture before converting them into iPS cells using the methods created by Yamanaka.
In addition to providing an alternative to embryonic stem cells for potential use in regenerating diseased tissues, iPS cells are being used to learn more about diseases, especially diseases driven by mutated genes.
Unlike the skin cells from which they originated, the human iPS cells created from FOP patients show increased cartilage formation and increased bone mineralization, two critical steps that are necessary to form mature bone. Bone morphogenetic proteins (BMPs) play a central role in the bone formation within muscle. FOP results from a gene mutation that causes a defect in the receptor protein to which BMPs bind, thereby increasing bone formation.
"These cells will be a key tool for finding ways to stimulate and control human bone growth for regenerative medicine or bone repair," Hsiao said. "The iPS cells may also help us identify treatments for more common diseases, such as atherosclerosis and vascular calcification, because the same bone morphogenetic protein pathways are involved in these medical conditions."
###
The work was a joint effort between Hsiao's lab group at UCSF; Bruce Conklin, MD, PhD, Hsiao's former postdoctoral mentor at the UCSF-affiliated Gladstone Institutes; and a research team at Kyoto University, led by Makoto Ikeya, PhD, and Junya Toguchida, MD, PhD. The research was supported by the National Institutes of Health, the California Institute for Regenerative Medicine, the March of Dimes, and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital.
Stem cells used to model disease that causes abnormal bone growth
UCSF-led study sheds light on muscle-to-bone transformation
2014-01-08
ELSE PRESS RELEASES FROM THIS DATE:
Color-coded cells reveal patchwork patterns of X chromosome silencing in female brains
2014-01-08
Color-coded cells reveal patchwork patterns of X chromosome silencing in female brains
Producing brightly speckled red and green snapshots of many different tissues, Johns Hopkins researchers have color-coded cells in female mice to display which of their two X chromosomes ...
Roche reports new method for efficiently transporting antibodies across the blood-brain barrier
2014-01-08
Roche reports new method for efficiently transporting antibodies across the blood-brain barrier
Results published in Neuron demonstrate efficacy in preclinical mouse models of Alzheimer's disease
Today the scientific journal Neuron published results on the Roche-designed ...
An improved, cost-effective catalyst for water-splitting devices
2014-01-08
An improved, cost-effective catalyst for water-splitting devices
Solar energy appears to be the only form of renewable that can be exploited at level that matches the world's growing needs. However, it is equally necessary to find efficient ways to store ...
New research: Effects of eating half an avocado with lunch on satiety & desire to eat between meals
2014-01-08
New research: Effects of eating half an avocado with lunch on satiety & desire to eat between meals
Loma Linda University study explores the relationship between avocado consumption, satiety and blood sugar
IRVINE, Calif. (DATE) – New research published in the ...
LA BioMed study finds daily antibiotics most effective in preventing recurrent urinary tract infection
2014-01-08
LA BioMed study finds daily antibiotics most effective in preventing recurrent urinary tract infection
Cranberry pills, estrogen and acupuncture also found to be helpful
LOS ANGELES (Jan. 8, 2014) – While ...
Researchers propose alternative way to allocate science funding
2014-01-08
Researchers propose alternative way to allocate science funding
Researchers in the United States have suggested an alternative way to allocate science funding. The method, which is described in EMBO reports, depends on a collective distribution of funding by ...
Medicine protects against strokes
2014-01-08
Medicine protects against strokes
It is well-known that anticoagulant medicine assists in the prevention of strokes. A large Danish study now shows that the medicine can also reduce the risk of death and brain damage when a stroke happens ...
Seniors moving to HCBS face more hospital risk
2014-01-08
Seniors moving to HCBS face more hospital risk
PROVIDENCE, R.I. [Brown University] — Seniors want greater access to home- and community-based long-term care services. Medicaid policymakers have been happy to oblige with new programs to help people move out of expensive ...
Chemical imaging brings cancer tissue analysis into the digital age
2014-01-08
Chemical imaging brings cancer tissue analysis into the digital age
A new method for analysing biological samples based on their chemical makeup is set to transform the way medical scientists examine diseased tissue.
When tests are carried out on a patient's tissue ...
Climate change: How does soil store CO2?
2014-01-08
Climate change: How does soil store CO2?
Carbon content in soil influences climate models
Previous studies have established that carbon binds to tiny mineral particles. In this latest study, published in Nature Communications, researchers have shown ...
LAST 30 PRESS RELEASES:
Thirty-year mystery of dissonance in the “ringing” of black holes explained
Less intensive works best for agricultural soil
Arctic rivers project receives “national champion” designation from frontiers foundation
Computational biology paves the way for new ALS tests
Study offers new hope for babies born with opioid withdrawal syndrome
UT, Volkswagen Group of America celebrate research partnership
New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll
Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes
University of Cincinnati Cancer Center presents research at AACR 2025
Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025
AACR: Researchers share promising results from MD Anderson clinical trials
New research explains why our waistlines expand in middle age
Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker
Chips off the old block
Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia
Cutting the complexity from digital carpentry
Lung immune cell type “quietly” controls inflammation in COVID-19
Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity
State and sociodemographic trends in US cigarette smoking with future projections
Young adults drive historic decline in smoking
NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research
Chimpanzee stem cells offer new insights into early embryonic development
This injected protein-like polymer helps tissues heal after a heart attack
FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology
In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity
Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects
A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions
AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate
Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative
Structure dictates effectiveness, safety in nanomedicine
[Press-News.org] Stem cells used to model disease that causes abnormal bone growthUCSF-led study sheds light on muscle-to-bone transformation