Lung airway stem cells awry in cystic fibrosis

Recent research from the University of Iowa suggests that people with cystic fibrosis have fewer of the stem cells that would normally repair the airway.

In most people, glands in the airway secrete bacteria-killing factors to help fight infection. These glands are also home to airway stem cells that rebuild the glands and keep them functioning normally. The Iowa team found that in people with CF, the airway stem cells had packed up and moved to the surface of airway rather than being nestled in the protective glands.

The team didn't find a clear cause and effect, but they suggest that with fewer airway stem cells, those glands are less able to repair themselves and secrete factors to help ward off infection. John Engelhardt, Roy J. Carver Chair in Molecular Medicine and professor and head of anatomy and cell biology who led the research, suggests that the next step might be to learn how to manipulate the environment, or stem cell niche, of those glands so that the stem cells will stay put and keep the glands functioning properly. Such a therapy could help prevent the infections that wreak such havoc on people with CF.

A University of Iowa press release quotes Engelhardt:

"This is the first demonstration that lung stem cell niches may be altered in CF." … "The future excitement of these findings relates to the potential of manipulating lung stem cells through neuropeptides or their inhibitors."

The work was published in the July 18 issue of July 18 issue of Journal of Clinical Investigation.

A.A.

Tracking stem cells using tricks learned in outer space

Stem cell science is set to get a boost from an unlikely source: outer space. It turns out that techniques devised to help telescopes peer through the blur of the earth's atmosphere could help scientists peak more deeply into tissues. If the technique, called adaptive optics or AO, works it might prove useful for scientists hoping to track the whereabouts of transplanted stem cells.

A group of researchers at the University of California, Santa Cruz, including CIRM grantee Joel Kubby, have formed the W. M. Keck Center for Adaptive Optical Microscopy, which will apply AO techniques to microscopes built for peering deep into tissues.

A press release from UCSC describes the project:

Principal investigator Joel Kubby, an associate professor of electrical engineering in the Baskin School of Engineering at UCSC, has worked on adaptive optics (AO) systems for large telescopes as well as for biological imaging. In astronomy, AO systems correct the blurring of telescope images caused by turbulence in the Earth's atmosphere. In microscopy, blurring is caused by the flowing cytoplasm of living cells.

"We can get beautiful images of cells close to the surface of the tissue, but if you want to go deep you're out of luck because of the degradation of the image. That was the motivation for this project," said co-investigator William Sullivan, professor of molecular, cell, and developmental biology at UC Santa Cruz. "For cell biologists, anything that improves imaging is a big deal, and this has the potential to open up vast areas of cell biology that have been opaque to us."

In stem cell research, for example, an important bottleneck in efforts to develop stem cell therapies has been the inability to follow injected stem cells and monitor their fates below the surface of the tissue. AO microscopy could solve this problem, and the California Institute for Regenerative Medicine (CIRM) has provided support for the work at UCSC, including funding that led to the development of the team's first AO microscope.

Knowing where a stem cell goes once it has been transplanted is critical to developing new therapies. Unless they go to where the damage is and stay there, those cells won't hold any long-term therapeutic benefit. Tracking cells within tissues could point to better ways of transplanting the cells and, eventually, to more effective therapies.

A.A.

A history of the stem cell lawsuit & what it meant to California scientists

Today U.S. District Judge Royce Lamberth dismissed a lawsuit that has been creating uncertainty for stem cell scientists for almost a year. The Washington Post quotes Lamberth's opinion:

“This Court, following the D.C. Circuit’s reasoning and conclusions, must find that defendants reasonably interpreted the Dickey-Wicker Amendment to permit funding for human embryonic stem cell research because such research is not ‘research in which a human embryo or embryos are destroyed,’ ” Lamberth wrote.

Here's some history on the lawsuit from this blog:

• What the embryonic stem cell research ban means to California researchers (8/27/2010)
• Government appeals stem cell ruling, claims harm to patients (8/31/2010)
• The ups and downs of federal funding for stem cell research (9/9/2010)
• Legal wrangling slows Stanford researcher's quest for a cure (9/15/2010)
• U.S. Appeals Court decision--good news, but not the final word (4/29/2011) 

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Discoverer of brain stem cells becomes president of ISSCR

The North County Times had a good story yesterday about Fred Gage's new role as the president of the International Society for Stem Cell Research. Gage is a renowned stem cell scientists at The Salk Institute for Biological Studies, which also wrote about his new role.

Gage was the first to show that people do, in fact, produce new brain cells after birth. In work that is especially close to my heart, he also showed that mice that get (to quote the 1999 press release) "regular voluntary exercise on running wheels" also grow more brain cells than sedentary mice.

More recently, Gage has had CIRM funding to carry out studies modeling human neurological diseases in a lab dish as a way of understanding and treating those diseases. We've blogged about his work here and here.

As the new president of ISSCR, which represents about 4,000 stem cell scientists internationally, Gage said he hoped to advocate for stem cell science to the public and to politicians. He also hopes to advance ISSCR's mission of moving basic stem cell discoveries into clinical therapies. He told the North County Times:

"There's been a lot of fantastic basic research that has been done," Gage said. "We realize that part of our mission as a society is to translate these basic science into clinical applications. We call it bench to bedside. We're thinking about ways to do this most effectively."…

"You have to have the basic biologists helping in this, but we need the clinicians too, even though they don't have the (scientific) knowledge," Gage said. "We need to bring them up to speed. And underlying all this, we need to have a very effective fundraising effort for the society."

Gage talked to CIRM about how stem cells can be used to mimic disease in a lab dish:



A.A.

Aggressive breast cancer treated with bone marrow stem cells

Last week brought a paper by Stanford researchers that has been a long, long time coming. It shows that 12-14 years after the experimental treatment, women with metastatic breast cancer benefited from high dose chemotherapy followed by transplantation of their own blood-forming stem cells. The paper was published online July 15 in Biology of Blood and Marrow Transplantation.

Back at the time when the group, which included CIRM grantee Irv Weissman, carried out this trial, doctors were rejecting high-dose chemotherapy for people with metastatic breast cancer. That therapy destroys the cancer, but also destroys the patient's bone marrow, which produces all blood and immune cells. That side effect would be deadly, but doctors can reinject bone marrow cells taken from patients before chemotherapy. This is the process that is used today for many types of cancers. However, doctors were finding that the whole bone marrow also contained some breast cancer cells. If those cells survived the transplantation they could spread and form a new, deadly cancer. So much for the chemotherapy.

Back when the Stanford scientists carried out their trial (between 1996 to 1998) Weissman had recently figured out how to purify the blood-forming stem cells in the bone marrow that are responsible for rebuilding the blood system. He and the team thought they could pull out just those cells from the patient's blood and use those cells to save the blood system after high-dose chemotherapy. If it worked, the chemotherapy would destroy the cancer, and the purified stem cells would save the blood system without reintroducing cancer cells lurking in the blood.

It all sounded good, but they were not sure whether their idea had worked until now. What they learned is that 23 percent of the women in their trial are still alive, compared to 9 percent of women who received unpurified stem cells.

A Stanford press release about the work quotes Weissman:

“Even with this small sample size, this paper demonstrates much-better overall and progression-free survival in those patients who received cancer-free stem cells.”

Senior author on the paper Judith Shizuru said in the release:

“Most people in the oncology community feel that this issue is a done deal, that high-dose chemotherapy does not work for patients with breast cancer. But our study suggests that the high-dose therapy strategy can be modified to include the use of cancer-free purified blood stem cells to yield better overall outcomes in women with advanced breast cancer.”

The authors are encouraging scientists to revisit high-dose chemotherapy for other cancers where it isn't traditionally offered. If it shows benefit for those patients it could open up a new form of therapy for a wide range of cancers.

This paper also highlights something that will continue to be true of all forms of stem cell research: It takes a long time to learn whether a therapy was truly effective. A decade from now we'll know whether the stem cell trials of today really worked. It's slow and frustrating, but papers like this one make the wait worth while.

A.A.

CIRM Bridges to Stem Cell Research students talk science in our new video

On July 8, 2011 the CIRM Bridges to Stem Cell Research trainees met in Burlingame, CA to share results from their research internships. Their enthusiasm for stem cell science made for a fun poster session where the students had a chance to share their internship research with other students, with CIRM staff and board members, and with California stem cell scientists who attended.

This video gives an overview of what these students have been up to:



First established in 2009, the Bridges programs fund students at community colleges and California State schools to take stem cell classes and do internship projects in established stem cell research labs in industry or at University of California and other major university campuses. (This map shows the Bridges to Stem Cell Research programs in purple.) Given the expense of working with stem cells, students at these schools would likely never have had a chance to participate in this cutting edge research. And without that experience, these students would likely be shut out of careers in California's growing stem cell industry. 

A.A.

Guest blogger Alan Trounson — July’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

In the past month one paper struck me as especially important because it has the potential to alleviate a particularly nasty disability. Radiation therapy can buy time for patients with brain tumors, but the collateral damage it does to surrounding healthy tissue can cause problems with learning and memory, that grow worse over time. It is believed that this decline occurs because the radiation destroys the adult neural stem cells that should be repairing damage. When this happens to a child and you watch them decline mentally at an age when they should be advancing, it can be heart-breaking. That is why I chose to highlight a paper in which injected neural stem cells were able to repair radiation damage in rats and bring back their sensory abilities towards normal. (You can read our blog entry on this research here.)

This month’s literature continued to show progress in using stem cells to reproduce complex tissues made of multiple cell types, something that has always been a touchstone goal for regenerative medicine. One research team was able to grow functional small intestine on a biodegradable scaffold in mice (which we blog about here). Another was able to produce mucus glands with both the inner and outer structures that make up a normal gland (blogged about here).

With heart disease being a leading cause of disability it was good to see advances in heart tissue repair this month from two very different angles. One research team developed a much more efficient way to drive embryonic stem cells to become heart muscle cells, which is the type of cell needed to repair tissue damaged or weakened from a heart attack or congestive heart failure. The other team discovered a compound that can be injected like a drug and that can activate the few adult heart stem cells we all have to be better at repairing tissue (here's our blog about that work).

I hope you find the somewhat longer descriptions in my full report interesting.