New stem cell growth strategy could yield better way to treat brain lesions
Durham, NC — Researchers have found a new way to increase the survival of stem cells injected into the brain. The discovery might one day prove useful in developing new treatments for neurological disorders — especially brain lesions, which among other things can provoke seizures and indicate multiple sclerosis or certain forms of cancer.
The study was performed by Sushma Chaubey, Ph.D., and John H. Wolfe, V.M.D., Ph.D., of the Children's Hospital of Philadelphia’s Research Institute and the University of Pennsylvania School of Veterinary Medicine. It appears in the current issue of STEM CELLS Translational Medicine.
Reduced oxygen levels could double neural stem cells’ chance of survival
Durham, NC — Decreasing the amount of oxygen traditionally used when culturing stem cells for use in neurological therapies could drastically affect their survival rate. In fact, it could double it, according to a new study released today in STEM CELLS Translational Medicine.
“Cells are usually cultured in the lab in a 20 percent oxygen environment, a level far removed from the in vivo situation. This is particularly true in the central nervous system, where oxygen tensions — that is, the concentration of oxygen at a specific pressure — are normally around 3 percent,” said Sybil Stacpoole, M.D., Ph.D., lead author on the paper by a team of researchers from the Universities of Cambridge and Edinburgh.
Stem cell-engineered artificial trachea gives toddler new lease on life
May 2013 — A toddler born with a rare, fatal congenital abnormality in which her trachea failed to develop has been given a new lease on life after receiving an artificial trachea last month that was grown in the lab from stem cells.
Discovery of age-reversing protein could lead to effective heart failure treatment
May 2013 — Researchers have identified a protein in the blood of mice and humans that may prove to be the first effective treatment for the form of age-related heart failure that affects millions of Americans.
Stem cell researchers move toward treatment for rare nerve disease
May 2013 — Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have used induced pluripotent stem (iPS) cells to advance disease-in-a-dish modeling of a rare genetic disorder called ataxia telangiectasia (A-T). Their discovery may lead to effective new treatments for the neurodegenerative disease.
Damage Removal by Alternate Proteasome in ESCs
“Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28”
Embryonic stem cells (ESCs) have been shown to contain relatively high levels of ‘damaged’ proteins such as carbonylated proteins (Hernebring et al 2006), which are eliminated upon differentiation and are also observed to accumulate in aging cells, (Hernebring et al 2006). Additionally, immunoproteasome subunit expression, required for the production of peptide antigens for display by antigen-presenting cells (Strehl et al) has been noted to be significantly altered during ESC differentiation (Atkinson and Collin et al), suggesting that the specific proteasomal subunits may be dynamically regulated during ESC self-renewal and differentiation. Now, in Scientific Reports, researchers from the laboratory of Thomas Nyström at the Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden have shown that damaged protein removal during ESC differentiation is associated with the induction of the proteasome activator PA28, normally associated with the immunoproteasome (Hernebring et al).
Modelling AD in iPSCs Provides Therapeutic Clues
“Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aß and Differential Drug Responsiveness”
Oligomerisation of amyloid-β peptide (Aβ) leading to amyloid plaques in the brain is thought to play a role in the pathogenesis of Alzheimer’s disease (AD) in humans (Kuo et al, Noguchi et al and Shankar et al) but the mechanism involved is still unclear. Induced pluripotent stem cell (iPSC) technology now provides a means to study the development of this disease and the effects of Aβ oligomers and will also allow for the screening of therapeutic drugs. To this end, researchers from the laboratory of Nobuhisa Iwata and Haruhisa Inoue have reported the derivation and neuronal/astroglial differentiation of iPSCs derived from patients carrying various AD-associated genetic mutations, and have found that Aβ oligomers are not proteolytically resistant and that docosahexaenoic acid (DHA) treatment attenuated cellular stress phenotypes of AD neural cells containing Aβ oligomers (Kondo et al).
Corrected iPSC-Mediated DMD Therapy
“An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells”
Induced pluripotent stem cell (iPSC)-derived myogenic progenitors are considered a possible treatment for Duchenne muscular dystrophy (DMD), a progressive and incurable neuromuscular disease. This would involve the ex vivo correction of the mutation in the Dystrophin gene which causes DMD, a strategy shown to be successful in mouse models of sickle cell anaemia (Hanna et al) and β-thalassaemia (Wang et al). In a recent report in Nature Communications, the laboratory of Rita C. R. Perlingeiro at the Lillehei Heart Institute, University of Minnesota, USA have combined an ex vivo genetic correction strategy and their efficient protocol to generate skeletal muscle stem/progenitor cells with significant regeneration potential (Darabi et al) to produce cells which have the capacity to promote substantial muscle regeneration in vivo accompanied by functional improvement (Filareto et al).
Hot Off the Press
| Damage Removal by Alternate Proteasome in ESCs |
“Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28” Embryonic stem cells (ESCs) have been shown to contain relatively high levels of ‘damaged’ proteins such as carbonylated proteins (Hernebring et al 2006), which are eliminated upon differentiation and are also observed to accumulate in aging cells, (Hernebring et al 2006). Additionally, immunoproteasome subunit expression, required for the production of peptide antigens for display by antigen-presenting cells (Strehl et al) has been noted to be significantly altered during ESC differentiation (Atkinson and Collin et al), suggesting that the specific proteasomal subunits may be dynamically regulated during ESC self-renewal and differentiation. Now, in Scientific Reports, researchers from the laboratory of Thomas Nyström at the Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden have shown that damaged protein removal during ESC differentiation is associated with the induction of the proteasome activator PA28, normally associated with the immunoproteasome (Hernebring et al). |
| Read more... |
| Modelling AD in iPSCs Provides Therapeutic Clues |
“Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aß and Differential Drug Responsiveness” Oligomerisation of amyloid-β peptide (Aβ) leading to amyloid plaques in the brain is thought to play a role in the pathogenesis of Alzheimer’s disease (AD) in humans (Kuo et al, Noguchi et al and Shankar et al) but the mechanism involved is still unclear. Induced pluripotent stem cell (iPSC) technology now provides a means to study the development of this disease and the effects of Aβ oligomers and will also allow for the screening of therapeutic drugs. To this end, researchers from the laboratory of Nobuhisa Iwata and Haruhisa Inoue have reported the derivation and neuronal/astroglial differentiation of iPSCs derived from patients carrying various AD-associated genetic mutations, and have found that Aβ oligomers are not proteolytically resistant and that docosahexaenoic acid (DHA) treatment attenuated cellular stress phenotypes of AD neural cells containing Aβ oligomers (Kondo et al).
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| Read more... |
| Corrected iPSC-Mediated DMD Therapy |
“An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells” Induced pluripotent stem cell (iPSC)-derived myogenic progenitors are considered a possible treatment for Duchenne muscular dystrophy (DMD), a progressive and incurable neuromuscular disease. This would involve the ex vivo correction of the mutation in the Dystrophin gene which causes DMD, a strategy shown to be successful in mouse models of sickle cell anaemia (Hanna et al) and β-thalassaemia (Wang et al). In a recent report in Nature Communications, the laboratory of Rita C. R. Perlingeiro at the Lillehei Heart Institute, University of Minnesota, USA have combined an ex vivo genetic correction strategy and their efficient protocol to generate skeletal muscle stem/progenitor cells with significant regeneration potential (Darabi et al) to produce cells which have the capacity to promote substantial muscle regeneration in vivo accompanied by functional improvement (Filareto et al).
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| Read more... |
| Breakthrough Discovery for Diabetes |
The exciting discovery of a new, naturally occurring hormone that induces dramatic reproduction of insulin-producing beta pancreatic cells, published in the April edition of Cell by Harvard’s Douglas Melton and Peng Yi,1 has the potential to revolutionise the way that Type 2 diabetes is treated. |
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| Adult Disease Model from iPSC Progeny |
“Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs” Modelling genetic disorders using induced pluripotent stem cells (iPSCs) is an emerging tool for researchers; however cells derived from iPSCs, such as cardiomyocytes (CMs), have not yet been qualified as useful models of adult disease phenotypes. Now researchers from the group of Huei-Sheng Vincent Chen at the Sanford-Burnham Medical Research Institute, California, USA have studied the inherited heart disease arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) (Calkins and Marcus) an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss in the right ventricle. From patient-specific mutation bearing fibroblasts they generated iPSCs and subsequently iPSC-CMs; finding that induction of adult-like metabolism has a critical role in establishing an adult-onset disease model (Kim et al). |
| Read more... |
