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.”

Building a Blueprint for the Human Brain

How does a brain blossom from a small cluster of cells into nature’s most powerful supercomputer? The answer has long puzzled scientists, but with new advances in stem cell biology, researchers are quickly mapping the complex suite of connections that together make up the brain.

UCLA scientists have developed a new system that can map the development of brain cells.

UCLA scientists have developed a new system that can map the development of brain cells.

One of the latest breakthroughs comes from Dr. Daniel Geschwind and his team at the University of California, Los Angeles (UCLA), who have found a way to track precisely how early-stage brain cells are formed. These findings, published recently in the journal Neuron, shed important light on what had long been considered one of biology’s black boxes—how a brain becomes a brain.

Along with co-lead authors and UCLA postdoctoral fellows Drs. Luis de la Torre-Ubieta and Jason Stein, Geschwind developed a new system that measures key data points along the lifetime of a cell, as it matures from an embryonic stem cell into a functioning brain cell, or neuron. These new data points, such as when certain genes are switched on and off, then allow the team to map how the developing human fetus constructs a functioning brain.

Geschwind is particularly excited about how this new information can help inform how complex neurological conditions—such as autism—can develop. As he stated in a news release:

“These new techniques offer extraordinary promise in the study of autism, because we now have an unbiased and genome-wide view of how genes are used in the development of the disease, like a fingerprint. Our goal is to develop new treatments for autism, and this discovery can provide the basis for improved high-efficiency screening methods and open up an enormous new realm of therapeutic possibilities that didn’t exist before.”

This research, which was funded in part by a training grant from CIRM, stands to improve the way that scientists model disease in a dish—one of the most useful applications of stem cell biology. To that end, the research team has developed a program called CoNTEXT that can identify the maturity levels of cells in a dish. They’ve made this program freely available to researchers, in the hopes that others can benefit. Said de la Torre-Ubieta:

“Our hope is that the scientific community will be able to use this particular program to create the best protocols and refine their methods.”

Want to learn more about how stem cell scientists study disease in a dish? Check out our pilot episode of “Stem Cells in your Face.”

Cells Behaving Badly: Rogue Stem Cells Set Stage for Lung Cancer, CIRM-Funded Study Finds

Occasionally, too much of a good thing can turn bad, an adage confirmed in a study published today by UCLA scientists.

Led by Dr. Brigitte Gomperts, a team of stem cell experts have honed in on how adult stem cells residing in the lung spring into action in order to repair damaged tissue. Normally, this process is vital for maintaining tissue health. But sometimes, things can go awry—thus setting the stage for cancer.

Scientists have hypothesized that some type of regulatory molecule pulled the strings—launching adult stem cells into action after injury or disease—but identifying that molecule had proven far more difficult.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

In this study, published online today in the journal Stem Cell, Dr. Gomperts and her team believe they have found this molecular puppet master: a class of molecules called reactive oxygen species, or ROS.

Recently, scientists observed low levels of ROS to play a role in maintaining a variety of cellular functions. They had also noticed that while low-to-moderate ROS levels were essential, any spike in ROS appeared to have a toxic effect on the cell.

In this study, which was supported by a CIRM New Faculty Award, the UCLA team found that a ‘dynamic flux’ in ROS levels from low to moderate helped drive adult stem cells to grow and divide at regular rates and repair damaged tissue. But when ROS levels got too high, the stem cells started dividing out of control, leading to what Gomperts called “pre-cancerous lesions.”

As she explained in today’s news release:

“Low ROS is what keeps stem cells in a ready state so that your body is poised and ready to respond to injury and repair. Loss of this ROS regulation leads to pre-cancerous lesions.”

Importantly, the team noted that many environmental factors are linked to an increase in ROS levels—such as exposure to cigarette smoke, smog or pathogens. Lung cancer remains the deadliest form of cancer in the United States. Therefore, finding a way to identify the cancer in this early, pre-cancerous stage, is crucial for reducing the risk of death.

As Gomperts put it:

“Now, with this precancerous model in place, we can begin looking for what we call ‘driver mutations,’ or those specific changes that take the pre-cancerous lesion to full-blown cancer.”

Gomperts is optimistic that this ‘personalized’ approach to drug discovery will lead to more effective therapies:

“There are likely multiple ways for a patient to get a pre-cancerous lesion so the process could be different amongst different groups of people. Imagine a personalized way to identify what pathways have gone wrong in a patient, so that we could target a therapy to that individual.”

The Great Divide: CIRM-Funded Research Resolves Controversy over the Regenerative Powers of Heart Cells

The human heart contains approximately 3 billion beating heart cells. But is this number predetermined from birth? Or do these cells have the ability to divide and replicate?

These questions have long dogged scientists—who initially thought that heart muscle cells, or cardiomyocytes, were incapable of dividing. But in recent years, new evidence came to light indicating that heart cells are, in fact, capable of regenerating. But how, or why, or even to what extent, remained a mystery.

MADAM, a new genetics-based approach to studying stem cells, can directly detect the moment that a heart cell divides.

MADAM, a new genetics-based approach to studying stem cells, can directly detect the moment that a heart cell divides.

Researchers employed a variety of techniques to try and answer this question—one group even tried carbon dating (a technique generally reserved for dating archaeological remains) to pinpoint the age of a human’s heart cells—but to no avail.

So Dr. Reza Ardehali and his team at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research tried something new.

Published online recently in the Proceedings of the National Academy of Sciences, they developed a new genetics-based approach that could directly detect the moment that a heart cell divided. They called this technique the mosaic analysis with double markers, or MADAM.

Using the MADAM technique, the researchers observed in mouse models the timing and frequency by which heart cells grow and proliferate. In so doing, they found that—while rare after the first month of life—cardiomyocytes do divide within the heart in a symmetrical fashion. Specifically, the team measured a regeneration rate of just under one percent per year.

These findings, which were supported by a CIRM Grant, are essential for any future clinical studies into heart regeneration, as they can now take into account the existing regenerative capabilities of the heart. As Dr. Ardehali explained in the news release:

“This is a very exciting discovery because we hope to use this knowledge to eventually be able to regenerate heart tissue. The goal is to identify the molecular pathways involved in symmetric division of cardiomyocytes and use them to induce regeneration to replenish heart muscle tissue after disease or injury.”