Stem Cell Stories that Caught our Eye: What’s the Best Way to Treat Deadly Cancer, Destroying Red Blood Cells’ Barricade, Profile of CIRM Scientist Denis Evseenko

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.

Stem Cells vs. Drugs for Treating Deadly Cancer. When dealing with a potentially deadly form of cancer, choosing the right treatment is critical. But what if that treatment also poses risks, especially for older patients? Could advances in drug development render risky treatments, such as transplants, obsolete?

That was the focus of a pair of studies published this week in the New England Journal of Medicine, where a joint Israeli-Italian research team investigated the comparative benefits of two different treatments for a form of cancer called multiple myeloma.

Multiple myeloma attacks the body’s white blood cells. While rare, it is one of the most deadly forms of cancer—more than half of those diagnosed with the disease do not survive five years after being diagnosed. The standard form of treatment is usually a stem cell transplant, but with newer and better drugs coming on the market, could they render transplants unnecessary?

In the twin studies, the research team divided multiple myeloma patients into two groups. One received a combination of stem cell transplant and chemotherapy, while the other received a combination of drugs including melphalan, prednisone and lenalidmomide. After tracking these patients over a period of four years, the research team saw a clear advantage for those patients that had received the transplant-chemotherapy treatment combination.

To read more about these twin studies check out recent coverage in NewsMaxHealth.

Breaking Blood Cells’ Barricade. The process whereby stem cells mature into red blood cells is, unfortunately, not as fast as scientists would like. In fact, there is a naturally occurring barrier that keeps the production relatively slow. In a healthy person this is not necessarily a problem, but for someone in desperate need of red blood cells—it can prove to be very dangerous.

Luckily, scientists at the University of Wisconsin-Madison have found a way to break through this barrier by switching off two key proteins. Once firmly in the ‘off’ position, the team could boost the production of red blood cells.

These findings, published in the journal Blood, are critical in the context of disease anemia, where the patient’s red blood cell count is low. They also may lead to easier methods of stocking blood banks.

Read more about this exciting discovery at HealthCanal.

CIRM Scientist on the Front Lines of Cancer. Finally, HealthCanal has an enlightening profile of Dr. Denis Evseenko, a stem cell scientist and CIRM grantee from the University of California, Los Angeles (UCLA).

Born in Russia, the profile highlights Evseenko’s passion for studying embryonic stem cells—and their potential for curing currently incurable diseases. As he explains in the article:

“I had a noble vision to develop progressive therapies for the patient. It was a very practical vision too, because I realized how limited therapeutic opportunities could be for the basic scientist, and I had seen many great potential discoveries die out before they ever reached the clinic. Could I help to create the bridge between stem cells, research and actual therapeutics?”

Upon arriving at UCLA, Evseenko knew he wanted to focus this passion into the study of degenerative diseases and diseases related to aging, such as cancer. His bold vision of bridging the gap between basic and translational research has earned him support not only from CIRM, but also the National Institutes of Health and the US Department of Defense, among others. Says Evseenko:

“It’s my hope that we can translate the research we do and discoveries we make here to the clinic to directly impact patient care.”

Creaky Cell Machinery Affects the Aging Immune System, CIRM-Funded Study Finds

Why do our immune systems weaken over time? Why are people over the age of 60 more susceptible to life-threatening infections and many forms of cancer? There’s no one answer to these questions—but scientists at the University of California, San Francisco (UCSF), have uncovered an important mechanism behind this phenomenon.

Reporting in the latest issue of the journal Nature, UCSF’s Dr. Emmanuelle Passegué and her team describe how blood and immune cells must be continually replenished over the lifetime of an organism. As that organism ages the complex cellular machinery that churns out new cells begins to falter. And when that happens, the body can become more susceptible to deadly infections, such as pneumonia.

As Passegué so definitively put it in a UCSF news release:

“We have found the cellular mechanism responsible for the inability of blood-forming cells to maintain blood production over time in an old organism, and have identified molecular defects that could be restored for rejuvenation therapies.”

The research team, which examined this mechanism in old mice, focused their efforts on hematopoetic stem cells—a type of stem cell that is responsible for producing new blood and immune cells. These stem cells are present throughout an organism’s lifetime, regularly dividing to preserve their own numbers.

Molecular tags of DNA damage are highlighted in green in blood-forming stem cells. [Credit: UCSF]

Molecular tags of DNA damage are highlighted in green in blood-forming stem cells. [Credit: UCSF]

But in an aging organism, these cells’ ability to generate new copies is not as good as it used to be. When the research team dug deeper they found a key bit of cellular machinery, called the mini-chromosome maintenance helicase, breaks down. When that happens, the DNA inside the cell can’t replicate itself properly—and the newly generated cell is not running on all cylinders.

One of the first things that these old stem cells lose as a result is their ability to make B cells. B cells, a key component of the immune system, normally make antibodies that fight infection. As B cell numbers dwindle in an aging organism, so too does their ability to fight infection. As a result the organism’s risk for contracting dangerous illnesses skyrockets.

This research, which was funded in part by CIRM, not only informs what goes wrong in an aging organism at the molecular level, but also points to new targets that could keep these stem cells functioning at full capacity, helping promote so-called ‘healthy aging.’ As Passegué added:

“Everybody talks about healthier aging. The decline of stem-cell function is a big part of age-related problems. Achieving longer lives relies in part on achieving a better understanding of why stem cells are not able to maintain optimal functioning.”

Stem cell stories that caught our eye: young blood, cord blood, and blood cancers

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.

Pinning down young blood’s rejuvenating power. A trio of studies in the past week provided more evidence that giving older mice the blood of younger mice can rejuvenate some aspect of their function to a younger state. This has been shown for some years with various tissues, such as CIRM grantee Irina Conboy’s work at UC Berkeley looking at revitalizing older muscle. The recent studies all showed improvement in various aspects of brain function. Most important, the studies started to uncover some reasons for why the young blood could be beneficial when introduced into older animals. Conboy has suggested that one thing it does is provide an environment that lets muscle stem cells do a better job. The three current teams’ work suggests there are probably many factors at play in the young blood. The Boston Globe focused on the work of the Harvard team but puts all three projects in perspective. The San Francisco Business Times focused on the Stanford work and includes an extensive Q&A with the lead researcher.

Expanding cord blood could expand uses. The blood-forming stem cells found in umbilical cord blood have proven extremely valuable as a part of therapy for certain blood cancers. The problem with them is there just are not enough of them in a single cord to treat anyone large than a nine or 10-year-old child. That means when an adult needing a blood stem cell transplant can’t find a matching adult donor and has to resort to cord blood, they receive cells from two cords doubling the chance for severe side effect. Now, a team at Mount Sinai School of Medicine in New York has found a way to get cord blood stem cells to proliferate in the lab in greater numbers than anyone has in the past. They accomplished the trick by resetting the genetic switches that turn genes on and off. Genetic Engineering and Biotechnology News ran a description of the work.

Deciding on banking cord blood. I handle many desperate patient calls here at CIRM, and occasionally get a call from a parent wanting advice about banking their soon-to-be-born child’s cord blood. While I never offer specific advice, I do try to talk through a few factual issues for them to consider, such as the limitation on the number of cells in the cord discussed above. In this Huffington Post blog a mom walks through her family’s decision process for two different pregnancies that came to different, though pretty logical, conclusions for each. She raises many important considerations. However, note that toward the end when she talks about research “advancing” for several diseases, for all those diseases many more years of research will be needed before cord blood therapies become a reality if they ever do.

Blood cancers vs. blood stem cells. One of the difficulties of treating blood cancers is you often end up killing off the vital blood forming stem cells at the same time you destroy the cancer cells. A team at Dartmouth has developed a method to make it easier to distinguish between the stem cells and the cancer cells. Knowing this difference should help researchers find more specific cancer therapies that can destroy the cancer without harming the needed stem cells. Science Codex posted the press release from the medical school. You can read about projects CIRM funds in the field on our leukemia fact sheet.

Don Gibbons