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Modeling Hypertrophic Cardiomyopathy in a Dish

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Image of cardiac fibers

Credit: Zhen Ma, University of California, Berkeley

Researchers have learned in recent years how to grow miniature human hearts in a dish. These “organoids” beat like the real thing and have allowed researchers to model many key aspects of how the heart works. What’s been really tough to model in a dish is how stresses on hearts that are genetically abnormal, such as in inherited familial cardiomyopathies, put people at greater risk for cardiac problems.

Enter the lab-grown human cardiac tissue pictured above. This healthy tissue comprised of the heart’s muscle cells, or cardiomyocytes (green, nuclei in red), was derived from induced pluripotent stem (iPS) cells. These cells are derived from adult skin or blood cells that are genetically reprogrammed to have the potential to develop into many different types of cells, including cardiomyocytes.


Wearable Ultrasound Patch Monitors Blood Pressure

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Placement of the blood pressure patch

Caption: Worn on the neck, the device records central blood pressure in the carotid artery (CA), internal jugular vein (Int JV) and external jugular vein (Ext JV).
Credit: Adapted from Wang et al, Nature Biomedical Engineering

There’s lots of excitement out there about wearable devices quietly keeping tabs on our health—morning, noon, and night. Most wearables monitor biological signals detectable right at the surface of the skin. But, the sensing capabilities of the “skin” patch featured here go far deeper than that.

As described recently in Nature Biomedical Engineering, when this small patch is worn on the neck, it measures blood pressure way down in the central arteries and veins more than an inch beneath the skin [1]. The patch works by emitting continuous ultrasound waves that monitor subtle, real-time changes in the shape and size of pulsing blood vessels, which indicate rises or drops in pressure.


Precision Medicine: Making Warfarin Safer

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Blood sample for PT INR test, diagnosis for coagulation disease

Caption: Finding the right dose of the drug warfarin can be tricky, even with this standard test to measure how fast a person’s blood clots.
Credit: Thinkstock/jarun011

Every year, thousands of older Americans require emergency treatment to stop bleeding caused by taking warfarin, a frequently prescribed blood-thinning pill. My own mother received this drug in her later years, and her doctors encountered significant challenges getting the dose right. The problem is too much warfarin causes potentially serious bleeding, while too little leaves those who need the drug vulnerable to developing life-threatening clots in their legs or heart. The difference between too little and too much is distressingly small. But what if before writing a prescription, doctors could test for known genetic markers to help them gauge the amount of warfarin that a person should take?

Such tests have been available to doctors and patients for a few years, but they have not been widely used. The recent results of a national clinical trial offer some of the most convincing evidence that it’s time for that to change. In this study of 1,650 older adults undergoing elective hip or knee surgery, patients whose genetic makeup was used to help determine their dose of warfarin were less likely to suffer adverse events, including major bleeding. This trial marks an encouraging success story for the emerging field of pharmacogenomics, the study of how the variations in our genes affect our responses to medicines.


Ebola Virus: Lessons from a Unique Survivor

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Ebola virus

Caption: Ebola virus (green) is shown on cell surface.
Credit: National Institutes of Allergy and Infectious Diseases, NIH

There are new reports of an outbreak of Ebola virus disease in the Democratic Republic of Congo. This news comes just two years after international control efforts eventually contained an Ebola outbreak in West Africa, though before control was achieved, more than 11,000 people died—the largest known Ebola outbreak in human history [1]. While considerable progress continues to be made in understanding the infection and preparing for new outbreaks, many questions remain about why some people die from Ebola and others survive.

Now, some answers are beginning to emerge thanks to a new detailed analysis of the immune responses of a unique Ebola survivor, a 34-year-old American health-care worker who was critically ill and cared for at the NIH Special Clinical Studies Unit in 2015 [2]. The NIH-led team used the patient’s blood samples, which were drawn every day, to measure the number of viral particles and monitor how his immune system reacted over the course of his Ebola infection, from early symptoms through multiple organ failures and, ultimately, his recovery.

The researchers identified unexpectedly large shifts in immune responses that preceded observable improvements in the patient’s symptoms. The researchers say that, through further study and close monitoring of such shifts, health care workers may be able to develop more effective ways to care for Ebola patients.


Regenerative Medicine: Making Blood Stem Cells in the Lab

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Endothelial cells becoming hematopoietic stem cells

Caption: Arrow in first panel points to an endothelial cell induced to become hematopoietic stem cell (HSC). Second and third panels show the expansion of HSCs over time.
Credit: Raphael Lis, Weill Cornell Medicine, New York, NY

Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.

A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).

Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.


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