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iPS cells

Bioengineering: Big Potential in Tiny 3D Heart Chambers

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iPS human heart

Caption: Heart microchamber generated from human iPS cells; cardiomyocytes (red), myofibroblasts (green), cell nuclei (blue) 
Credit: Zhen Ma, University of California, Berkeley

The adult human heart is about the size of a large fist, divided into four chambers that beat in precise harmony about 100,000 times a day to circulate blood throughout the body. That’s a very dynamic system, and also a very challenging one to study in real-time in the lab. Understanding how the heart forms within developing human embryos is another formidable challenge. So, you can see why researchers are excited by the creation of tiny, 3D heart chambers with the ability to exist (see image above) and even beat (see video below) in a lab dish, or as scientists  say “in vitro.”

iPS heart cells video

Credit: Zhen Ma et al., Nature Communications

To achieve this feat, an NIH-funded team from University of California, Berkeley, and Gladstone Institute of Cardiovascular Disease, San Francisco turned to human induced pluripotent stem (iPS) cell technology. The resulting heart chambers may be miniscule—measuring no more than a couple of hair-widths across—but they hold huge potential for everything from improving understanding of cardiac development to speeding drug toxicity screening.


The Acid Test: Turning Regular Cells Into Stem Cells

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Green blobs on a grey background

Caption: A new type of stem cells, called STAPs.
Credit:
Haruko Obokata, RIKEN Ctr. for Dev. Biol., Kobe, Japan

Updated July 2, 2014: Since these two papers were published in the journal Nature, more than a dozen research teams have been unable to replicate the STAP findings. On April 1, RIKEN found the main author Haruko Obokata guilty of scientific misconduct. On July 2, Nature accepted requests from all co-authors to retract the papers and published an editorial discussing the retractions.

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Taking a 30-minute soak in a bath of acid might not sound like a good thing. But it happens to be the latest—and the most shockingly simple—strategy for creating stem cells.

The powerful appeal of stem cells for science and medicine lies in the fact that they are both self-renewing and pluripotent, which means they can develop into almost any type of cell in the body. Stem cell technology offers an essentially limitless supply of specialized cells to researchers for exploring the fundamentals of biology, screening for new drugs, and developing new ways to regenerate damaged tissue and repair diseased organs.


Reprograming Adult Cells to Produce Blood Vessels

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Green mesh with blue dots over a thick red mesh

Caption: New network of blood vessels (green) grown from reprogrammed adult human cells (blue: connective tissue, red: red blood cells)
Credit: Reproduced from R. Samuel et al, Proc Natl Acad Sci U S A. 2013;110:12774-9.

Individuals with heart disease, diabetes, and non-healing ulcers (which can lead to amputation) could all benefit greatly from new blood vessels to replace those that are diseased, damaged, or blocked. But engineering new blood vessels hasn’t yet been possible. Although we’ve learned how to reprogram human skin cells or white blood cells into so-called induced pluripotent stem (iPS) cells—which have the potential to develop into different cell types—we haven’t really had the right recipe to nudge those cells down a path toward blood vessel development.

But now NIH-funded researchers at Massachusetts General Hospital in Boston have taken another step in that direction.


Exploiting Stem Cell Stickiness for Sorting

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Photo of purple web-like objects adjacent to photo of a gloved hand holding a clear device with green lines, making it look like a circuit board.

Caption: Adult human fibroblast cells (left) are reprogramed into human induced pluripotent stem cells
(iPS cells). The iPS cells have a characteristic stickiness that lets them to adhere to sorting devices
(right) with different strengths than other cells.
Credit: Ankur Singh and Andres Garcia, Institute for Bioengineering & Bioscience, Georgia Tech

There is much excitement about the potential of stem cells for many applications, including regenerative medicine and treating human diseases. But growing pure cultures of stem cells by reprograming adult cells—like human fibroblasts—into a less differentiated cell type called a human induced Pluripotent Stem cell (iPS cell), is a tricky business. These stem cell cultures are often contaminated with other normal cells that do not have the same coveted therapeutic potential. Manually sorting these stem cells is time consuming and difficult; using chemical approaches can damage the DNA inside. Now, we have a better option: NIH funded researchers from the Georgia Institute of Technology in Atlanta have invented a cell-sorting device that exploits specific characteristics of iPS cells.

iPS cells have a characteristic ‘stickiness’ that allows them to adhere to surfaces inside the sorting chip with different strengths than other cells. This stickiness is due to a signature set of proteins on the surface of these stem cells. Normal cells are coated in other proteins that give their surfaces different adhesive properties.

The researchers say the method is gentle, efficient, rapid, and generates collections of stem cells that are 95–99% pure.

Reference:

Adhesion strength-based, label-free isolation of human pluripotent stem cells. Singh A, Suri S, Lee T, Chilton JM, Cooke MT, Chen W, Fu J, Stice SL, Lu H, McDevitt TC, García AJ. Nat Methods. 2013 May;10(5):438-44.

NIH support: National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke; National Cancer Institute


New Prize Celebrates Biology Breakthroughs

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Faces of the NIH grantees receiving the Breakthrough Prize in the Life Sciences (as listed below)

NIH grantees receiving the Breakthrough Prize in the Life Sciences
(in order as listed below)

The brand new $3 million Breakthrough Prize in the Life Sciences [1] delivered a very nice reward and well deserved recognition to eleven exceptionally creative scientists who have devoted their careers to biology and medicine. And, with five awards to be given each year, I hope this inspires other life scientists to embark on innovative and high-risk endeavors.

For this inaugural round, I’m proud to say that nine of the eleven winners were NIH grant recipients—some for more than three decades. Now, you may not have heard of most of these scientists. Quite frankly, that’s a shame. These folks have discovered fundamental principles of biology—everything from cancer causing genes to techniques for creating stem cells. These discoveries have boosted our understanding of health and disease, and led to the development of many drugs and therapies.

So these individuals really should be household names—and more of that kind of recognition would be a good thing to inspire youth to explore careers in science. In the United States, virtually everyone can list names of multiple movie stars and athletes, but two-thirds of Americans can’t name a single living scientist [2].


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