Stage fright: don't get over it, get used to it

Many can feel empathy with the situation Banerjee describes: facing “a room full of scientists, who for whatever reason, did not look very happy that Read more

Beyond birthmarks and beta blockers, to cancer prevention

Ahead of this week’s Morningside Center conference on repurposing drugs, we wanted to highlight a recent paper in NPJ Precision Oncology by dermatologist Jack Arbiser. It may represent a new chapter in the story of the beta-blocker propranolol. Several years ago, doctors in France accidentally discovered that propranolol is effective against hemangiomas: bright red birthmarks made of extra blood vessels, which appear in infancy. Hemangiomas often don’t need treatment and regress naturally, but some can lead Read more

Drying up the HIV reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo, the brain or the Read more

iPS cells

Fetal alcohol cardiac toxicity – in a dish

Alcohol exposure is known to perturb fetal heart development; half of all children with fetal alcohol syndrome have congenital heart defects, such as arrhythmias or structural abnormalities. Chunhui Xu and colleagues recently published a paper in Toxicological Scienceson how human cardiac muscle cells, derived from iPS (induced pluripotent stem cells), can be used as a model for studying the effects of alcohol.

Alcohol-induced cardiac toxicity is usually studied in animal models, but human cells are different, and a cell-culture based approach could make it easier to study the effects of alcohol and possible interventions more easily.

Red shows toxic effects of alcohol on iPS-derived cardiomyocytes

Xu and her colleagues observed that high levels of alcohol damaged cardiac muscle cells and put them under oxidative stress. But even at relatively low concentrations of alcohol, the researchers also saw perturbations in cells’ electrical activity and the ability to contract, which reasonably matches the effects of alcohol on human heart development. The lowest level tested was 17 millimolar – the legal limit for driving in most states (0.08% blood alcohol content). Read more

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Stay out, stray stem cells

Despite the hubbub about pluripotent stem cells’ potential applications, when it comes time to introduce products into patients, the stem cells are actually impurities that need to be removed.

That’s because this type of stem cell is capable of becoming teratomas – tumors — when transplanted. For quality control, researchers want to figure out how to ensure that the stem-cell-derived cardiac muscle or neural progenitor or pancreas cells (or whatever) are as pure as possible. Put simply, they want the end product, not the source cells.

Stem cell expert Chunhui Xu (also featured in our post last week about microgravity) has teamed up with biomedical engineers Ximei Qian and Shuming Nie to develop an extremely sensitive technique for detecting stray stem cells.PowerPoint Presentation

The technique, described in Biomaterials, uses gold nanoparticles and Raman scattering, a technology previously developed by Qian and Nie for cancer cell detection (2007 Nature Biotech paper, 2011 Cancer Research paper on circulating tumor cells). In this case, the gold nanoparticles are conjugated with antibodies against SSEA-5 or TRA-1-60, proteins that are found on the surfaces of stem cells. Read more

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Addendum on CRISPR

An excellent example of the use of CRISPR gene editing technology came up at the Emory-Children’s Pediatric Research Center’s Innovation Conference this week.

Marcela Preininger, who is working with cardiomyocyte stem cell specialist Chunhui Xu, described her work (poster abstract 108) on cells derived from a 12 year old patient with an inherited cardiac arrhythmia syndrome: catecholaminergic polymorphic ventricular tachycardia or CPVT. Her team has obtained skin fibroblasts from the patient, and converted those cells into induced pluripotent stem cells, which can then be differentiated into cardiac muscle cells or cardiomyocytes.

Working with TJ Cradick, director of the Protein Engineering Facility at Georgia Tech, Preininger is testing out CRISPR gene editing as a means of correcting the defect in this patient’s cells, outside the body. Cradick says that while easy and efficient, RNA-directed CRISPR can be lower in specificity compared to the protein-directed TALEN technology.

From Preininger’s abstract:

Once the mutation has been corrected at the stem cell level, we will investigate whether the repaired (mutation-free) iPS cells can be differentiated into functional cardiomyocytes with normal Ca2+ handling properties, while closely monitoring the cells for mutagenic events. Pharmacological restoration of the normal myocardial phenotype will also be optimized and explored in our model.

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Souped-up method for iPS cell reprogramming

Peng Jin and collaborators led by Da-Hua Chen from the Institute of Zoology, Chinese Academy of Sciences have a new paper in Stem Cell Reports. They describe a souped-up method for producing iPS cells (induced pluripotent stem cells).

Production of iPS cells in the laboratory is becoming more widespread. Many investigators, including those at Emory, are using the technology to establish “disease in a dish” models and derive iPS cells from patient donations, turning them into tools for personalized medicine research.

Read more

Posted on by Quinn Eastman in Cancer, Immunology, Neuro Leave a comment