Regenerative Medicine: Making Blood Stem Cells in the Lab

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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LabTV: Curious About Parkinson’s Disease

Kinsley Belle

When the young scientist featured in this LabTV video first learned about induced pluripotent stem (iPS) cells a few years ago as an undergrad, he thought it would be cool if he could someday work with this innovative technology. Today, as a graduate student, Kinsley Belle is part of a research team that’s using iPS cells on a routine basis to gain a deeper understanding of Parkinson’s disease.

Derived from genetically reprogrammed skin cells or white blood cells, iPS cells have the potential to develop into many different types of cells, providing scientists with a powerful tool to model a wide variety of diseases in laboratory dishes.  At the University of Miami’s John P. Hussman Institute for Human Genomics, Belle and his colleagues are taking advantage of an iPS model of Parkinson’s disease to explore its molecular roots. Their goal? To use that information to develop better treatments or maybe even a cure for the neurodegenerative disorder that affects at least a half-million Americans.

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Bioengineering: Big Potential in Tiny 3D Heart Chambers

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.

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The Acid Test: Turning Regular Cells Into Stem Cells

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.

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Reprograming Adult Cells to Produce Blood Vessels

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. Continue reading