Stem cell videos make the grade

One amazing aspect of living in the era of social media is the incredible way information spreads. A butterfly batting its little orange wings in a monarch grove in Santa Cruz could influence a tweet of a blogger heard ‘round the world.

Or, in CIRM’s case, a few videos playing on YouTube could be used by a teacher heard 'round the world. In the past week a video about the difficulties of differentiating stem cells into therapeutically useful cell types has popped up in the curriculum of Harrison College, which offers a number of online and classroom courses. The video, which has been watched hundreds of times in the past week by those students, features Mark Mercola of Sanford-Burnham Medical Research Institute who is working to differentiate cardiac cells from human embryonic stem cells. Here’s that video:


In the past, a video about iPS cells featuring Jerome Zack from UCLA has made its way into college curricula, as has a video discussing the different types of stem cells with Stanford University’s Irv Weissman. These videos are all part of a stem cell basics CIRM put together to help educate people about stem cell research both in written form and in short videos.

Given the misperceptions of stem cell research in the public and in the media its nice to see these videos getting discovered and used for educational purposes.

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iPS cells from women create model for muscular dystrophy, X-linked diseases

Reprogrammed skin cells showing inactivated X in red

CIRM grantees at the University of California, Los Angeles have uncovered a feature of reprogrammed iPS cells that make them uniquely excellent for understanding diseases that arise from mutations on the X chromosome.

First some background. Men inherit an X chromosome from their mother, which contains many thousands of genes, and a Y from the father, which does little except confer manhood. Women inherit one X chromosome from each parent. Those female cells overcome their genetic overabundance by shutting down, at random, one of the two X chromosomes, putting the cells at genetic par with male cells.

But the two aren’t really equal. If men inherit a mutation on an X chromosome, it is present in every cell of the body and can cause muscular dystrophy, Rett Syndrome, color-blindness and other disorders. Women who inherit a mutation on an X chromosome from one parent will only show that mutation in half their cells. The other half of the body's cells, with the non-mutated chromosome active, can generally compensate.

So what does this have to do with reprogrammed cells and disease modeling? It turns out that the process of reprogramming skin cells into embryonic-like induced pluripotent stem cells doesn’t overturn the inactivated X. Reprogramming cells from a woman’s skin sample will produce two distinct types of iPS cell lines; half with one X active, and half of with the other X active. If one of those two chromosomes carries a mutation, say, for muscular dystrophy, some of those iPS lines will also display that mutation.

In a press release from UCLA, senior author Kathrin Plath said:

“This non-random pattern of X chromosome inactivation found in iPS cell lines has critical implications for clinical applications and disease modeling and could be exploited for a unique form of gene therapy for X-linked diseases.”

In a publication in Cell Stem Cell, Plath and her colleagues report that they created iPS cell lines from a woman who had inherited one X chromosome carrying a mutation that can cause muscular dystrophy. The other X chromosome had a normal copy of the gene. Scientists can now mature both groups of cells into skeletal muscle and compare the resulting tissue as a way of understanding—and perhaps one day treating—the devastating disease.

Cell Stem Cell: September 3, 2010
CIRM funding: Sean Sherman (TG2-01169), Kathrin Plath (RN1-00564), William Lowry (RS1-00259), Jerome Zack. (RL1-00681)

Engineered human stem cells destroy HIV infected cells

A group at the University of California, Los Angeles AIDS Institute has manipulated human blood-forming stem cells to fight HIV infected cells. The technique could conceivably be used to help the body fight any number of viral infections, the authors say.

The researchers started with blood-forming stem cells normally found in the bone marrow. These cells form all the cells of the human blood system including immune and red blood cells. They then inserted a gene from an immune cell of an HIV-infected individual. That protein can recognize the HIV virus and would ordinarily guide the person’s immune system to attack infected cells. In an HIV-infected person so few of those infection-fighting cells exist that the immune system can’t do its job. 

The idea was that blood-forming stem cells carrying that HIV-targeting protein would mature into an immune system primed to recognize and destroy HIV-infected cells.

To test their idea, the authors inserted the engineered stem cells into mice. These mice also had transplanted into them a human thymus, the organ that is responsible for making a population of infection-fighting cells called T cells. (The human T cells can’t mature properly in the mouse thymus. By implanting the mouse with a human thymus the researchers mimicked how the cells might behave in a human.) As they hoped, the blood-forming stem cells produced  human T cells that were able to kill HIV-infected cells.

The authors called this study a proof-of-principle, saying that by inserting different proteins into the blood-forming stem cells they could direct the immune system to attack Hepatitis, herpes or human papillomavirus.

A press release by UCLA quotes Jerome Zack, an author on the paper and CIRM grantee, as saying:

"This approach could be used to combat a variety of chronic viral diseases. It's like a genetic vaccine."

PLoS ONE, December 7, 2009
CIRM funding: Jerome Zack (RC1-00149)

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Early immune cells created from embryonic stem cells

Researchers at UC, Los Angeles have created cells that go on to form normal T cells out of human embryonic stem cells. What’s more, these cells were grown in the absence of animal feeder cells, which are usually needed to sustain embryonic stem cells. Avoiding potential contamination by such feeder cells is an important step in generating cells that can be transplanted into people. The researchers describe a series of steps that drive human embryonic stem cells to begin developing as T cells. When they transplanted the cells into mice with human thymus tissue, where T cells normally mature, those cells did mature into normal adult T cells. In addition, the group inserted genes into their immature T cells before transplantation and saw evidence that those genes were active in the mature, transplanted cells. This work brings researchers closer to creating cells that can be transplanted into people as a therapy for disorders of the immune system, including HIV/AIDS.

Stem Cells: October 30, 2008 (online publcation)
CIRM funding: Zoran Galic (RS1-00203), Aparna Subramaniana (T1-00005), Jerome Zack (RC1-00149)

Related Information: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA , Zack bio