Stem cell stories that caught our eye: better bone marrow transplants, turbo charging anti-inflammatory stem cells and Zika’s weapons

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Three steps to better BMT.  Bone marrow stem cell transplants (BMT) save the lives of many thousands of patients every year, but they also kill a significant number of the blood stem cell transplantcancer and immune disorder patients the procedure is intended to save. In order to make room in the bone marrow for new blood-forming stem cells, you first have to get rid of most of the stem cells already there, and the radiation and chemotherapy to do this proves too toxic for some patients. Also, donor marrow can contain immune cells from the donor that can attack the recipient causing Graft Versus Host Disease (GVHD), which can also be fatal.

Add this all together and physicians tend to save BMT for the patients with the most life threatening forms of the diseases.  A CIRM-funded team at Stanford has developed a three-step process that seems to dramatically reduce all those risks potentially opening up the procedure to less-sick patients including patients with life-altering, but not life-threatening, autoimmune diseases such as lupus and less severe forms of multiple sclerosis.

Experimenting in mice, they first used an antibody that attaches to a marker on blood stem cells called c-kit. But by itself that antibody could not get rid of enough of the stem cells. So, they added a second agent that blocked another protein, CD47, on the surface of blood stem cells. With that protein blocked, the animals own immune cells called macrophages, could destroy the blood stem cells. Then to make the donor cells safer, they used a technology they had developed many years ago to remove any straggler immune cells from the donor stem cells, thus drastically eliminating the chances for GVHD.

judith shizuru

Shizuru

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20 percent to effectively zero,” said senior author Judith Shizuru in a university press release posted by HealthCanal.

She went on to compare blood stem cell transplants to planting a new field of crops saying they were looking for a better way to first clear the field for planting and then a better way to do the planting. CIRM funded the team to develop the method for use with Severe Combined Immune Deficiency (SCID). The team published the current mouse study in the journal Science Translational Medicine.

 

Building a better anti-inflammatory stem cell.  Of the more than 700 stem cell therapy clinical trials underway around the world, more than half use the type of stem cell called a mesenchymal stem cell (MSC) found in bone marrow and fat—in marrow it resides alongside the blood-forming stem cells. Some of those trials are tapping into MSC’s ability to build bone, cartilage and blood vessels, but many are counting on their strong anti-inflammatory properties to fight autoimmune diseases.

When MSCs find themselves in an environment with pro-inflammatory proteins they respond by producing anti-inflammatory proteins. To enhance that effect some teams have bathed their MSC’s in pro-inflammatory proteins before injecting them into patients, but the effect of those proteins wears off quickly. So, a team led by CIRM-funded researcher Todd McDevitt at the Gladstone Institutes in San Francisco has bioengineered a way to make the effect long term.

McDevitt,-Todd-14

Gladstone used a CIRM Research Leadership award to recruit McDevitt from Georgia Tech

They loaded the pro-inflammatory proteins onto sugar-based particles that they imbedded in the middle of clusters of MSCs. The bioengineered complex slowly releases the cues to the MSCs and they in turn produced the desired anti-inflammatory proteins in greater quantities and much longer than in any other experiment.

 “A patient taking anti-inflammatory medication may not have high enough levels of inflammation to trigger the cells. We engineered the MSCs to ensure that they are consistently activated, so they can reliably dampen the immune response for longer,” said McDevitt in an institute press release.

The team published their research in Stem Cells Translational Medicine.

 

Stem cells used to identify Zika’s weapon.  It has been difficult for researchers to think about how to stop the Zika virus’ havoc on fetal brains without knowing how the virus does

Zika Virus

its evil deed. Now, a team at the University of Southern California (USC) has used fetal stem cells to discover two proteins that seem to be Zika’s key weapons.

Viruses often hijack our normal cell processes to enhance their ability to multiply and at the same time do harm to the host. In this case, the two proteins named NS4A and NS4B play key roles in the cell path for normal cell growth and disposal of damaged cells. When exploited by the virus, the two proteins result in cells being destroyed and not replaced.

“Those two viral proteins are ultimately the target for therapy development,” said USC’s Jae Jung in an article posted by Kaiser Health News.

As is typical with this news source, the author goes on to provide considerable high quality background about the Zika outbreak and efforts to find a vaccine or therapy, in this case quoting experts from Texas Children’s Hospital and Baylor.

 

Cloning fact timeline.  With the 20th anniversary last month of the birth of Dolly the sheep, the first cloned mammal, cloning seems to be much in discussion these days. So for

dolly-the-sheep

science nerds who like to keep back up facts handy CNN published a timeline of key events starting with the 1952 Nobel-winning discovery that you could replace the nucleus of a frog’s egg with the nucleus from another cell and still get the egg to develop into a tadpole. And 22 events later, it ends in 2014 with the first use of using cloning techniques to create stem cells that matched an adult.

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