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induced Pluripotent Stem cells

iMPCs: Cell Reprogrammers Take Aim at Liver Disease

Posted on by Dr. Francis Collins

Cross-section of mouse liver

Caption: Cross-section of mouse liver containing iMPC-derived human liver cells (red), some of which are proliferating (green). All cell nuclei appear blue.
Credit: Milad Rezvani, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco

Over the past few years, researchers have learned how to reprogram skin or blood cells into induced pluripotent stem cells (iPSCs), which have the ability to differentiate into heart, nerve, muscle, and many other kinds of cells. But it’s proven a lot more tricky to coax iPSCs (as well as human embryonic stem cells) to differentiate into mature, fully functional liver cells.

Now, NIH-funded researchers at the University of California, San Francisco (UCSF) and the Gladstone Institutes appear to have overcome this problem. They have developed a protocol that transforms human skin cells into mature liver cells that not only function normally in a lab dish, but proliferate after they’ve been transplanted into mice that model human liver failure [1]. This ability to proliferate is a hallmark of normal liver cells—and the secret to the liver’s astounding capacity to regenerate after infection or injury.


The Acid Test: Turning Regular Cells Into Stem Cells

Posted on by Dr. Francis Collins

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.


Yeast Reveals New Drug Target for Parkinson’s

Posted on by Dr. Francis Collins

Untreated yeast shows clumps of brightly colored spots, while treated yeast are more even in their color.
Caption: Left, yeast sick with too much α-synuclein, a protein that is implicated in Parkinson’s disease. Right, the same yeast cells after a dose of NAB, which seems to reverse the toxic effects of α-synuclein.
Credit: Daniel Tardiff, Whitehead Institute

Many progressive neurodegenerative disorders like Alzheimer’s, Huntington’s, and Parkinson’s disease, are characterized by abnormal clumps of proteins that clog up the cell and disrupt normal cellular functions. But it’s difficult to study these complex disease processes directly in the brain—so NIH-funded researchers, led by a team at the Whitehead Institute for Biomedical Research, Cambridge, MA, have turned to yeast for help.

Now, it may sound odd to study a brain disease in yeast, a microorganism long used in baking and brewing. After all, the brain is made up of billions of cells of many different types, while yeast grows as a single cell. But because the processes of protein production are generally conserved from yeast to humans, we can use this infinitely simpler organism to figure out what the proteins clumps are doing and test various drug candidates to halt the damage.


Exploiting Stem Cell Stickiness for Sorting

Posted on by Dr. Francis Collins

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


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