BIO International Panel Showed Stem Cell Science Poised to Make a Difference in Medical Practice Soon

When the biotechnology trade association began holding annual conferences in 1993, they drew 1,400 to the first event. This year BIO International expected nearly 20,000 here in San Diego. Among the dozens of concurrent sessions each day of this four-day scramble, stem cells got one track on one day this year. But listening to the progress being made by our presenters yesterday, our field is set to grow at the pace this meeting has—and could dominate the medical sessions here within the next decade.

995548_10151801308142804_405229409_n

After setting the scene with our opening panel yesterday, four subsequent panels confirmed the vast near-term potential painted by the opening speakers. They revealed a field maturing rapidly and starting to be a valued research tool of the bigger companies that have dominated the biotech industry, at the same time it is starting to deliver therapies to patients.

The second panel displayed the robust power of stem cells to model disease better than animal models ever could. These cells also let researchers dive much deeper into the genetic causes of disease, particularly diseases with multiple genes involved. Anne Bang from the Sanford-Burnham Institute mentioned her role in a consortium organized by the National Institutes of Health that is looking at the many genes involved in a type of heart weakening called left ventricular hypertrophy. Because different ethnicities tend to respond differently to drugs used for the condition, the consortium teams are creating iPS-type stem cell lines from 125 Caucasian patients and 125 African-American patients with various forms of the condition.

Their goal is to personalize and improve therapy across both patients groups. The way cells behave in the lab can tell the researchers much more relevant information than most animal models, so drugs developed based off their discoveries should have a better chance of success. All four panelists agreed that the field needs enough drugs developed with these tools to show that they do indeed have a better success rate. That track record should start to develop over the next few years.

The third panel talked about the shift in the medical mindset that will happen when genetically modified stem cells can change the care of chronic diseases from daily therapy to cures. Louis Bretton of Calimmune discussed how his company is trying to do this for HIV, which we blogged about yesterday when they announced promising first phase results from their first four patients. Faraz Ali of bluebird bio showed that his company has already made this life-changing shift for two patients with the blood disorder Beta Thalassemia. Like most patients with the disease they had been dependent on regular transfusions to survive, but when they received transplants of their own stem cells genetically modified to produce the correct version of a protein that is defective in the disease, they were able to live without transfusions.

The fourth panel provided proof that the field is maturing in that they discussed the many hurdles and pitfalls in taking those final steps to prepare a cell therapy to be a commercial product. The three big hurdles—financing, regulatory approval and reimbursement by insurers—all required creativity by the companies outlined in the two case studies. They are working through them but it is anything but a straightforward path. This is the area I hear the most hand wringing about in the halls of meetings in our field.

The last panel showed that one way around some of those end stage hurdles is to reach across borders. Four panelists discussed specific examples of ways international collaborations have accelerated their work toward developing therapies. CIRM has more than 20 collaborative agreements with funding agencies around the world, many of them painstakingly nurtured by our former president Alan Trounson. He gave the final presentation of the panel talking about one of his new projects, building an international stem cell bank with enough cell lines that almost everyone could get donor cells that were immunologically matched.

Our board chair, Jonathan Thomas, moderated the last panel and ended with a tribute to Alan noting that his build-out of our international program would be one of his many lasting legacies.
Don Gibbons

BIO International Panel Showed Stem Cell Science Poised to Make a Difference in Medical Practice Soon

When the biotechnology trade association began holding annual conferences in 1993, they drew 1,400 to the first event. This year BIO International expected nearly 20,000 here in San Diego. Among the dozens of concurrent sessions each day of this four-day scramble, stem cells got one track on one day this year. But listening to the progress being made by our presenters yesterday, our field is set to grow at the pace this meeting has—and could dominate the medical sessions here within the next decade.

995548_10151801308142804_405229409_n

After setting the scene with our opening panel yesterday, four subsequent panels confirmed the vast near-term potential painted by the opening speakers. They revealed a field maturing rapidly and starting to be a valued research tool of the bigger companies that have dominated the biotech industry, at the same time it is starting to deliver therapies to patients.

The second panel displayed the robust power of stem cells to model disease better than animal models ever could. These cells also let researchers dive much deeper into the genetic causes of disease, particularly diseases with multiple genes involved. Anne Bang from the Sanford-Burnham Institute mentioned her role in a consortium organized by the National Institutes of Health that is looking at the many genes involved in a type of heart weakening called left ventricular hypertrophy. Because different ethnicities tend to respond differently to drugs used for the condition, the consortium teams are creating iPS-type stem cell lines from 125 Caucasian patients and 125 African-American patients with various forms of the condition.

Their goal is to personalize and improve therapy across both patients groups. The way cells behave in the lab can tell the researchers much more relevant information than most animal models, so drugs developed based off their discoveries should have a better chance of success. All four panelists agreed that the field needs enough drugs developed with these tools to show that they do indeed have a better success rate. That track record should start to develop over the next few years.

The third panel talked about the shift in the medical mindset that will happen when genetically modified stem cells can change the care of chronic diseases from daily therapy to cures. Louis Bretton of Calimmune discussed how his company is trying to do this for HIV, which we blogged about yesterday when they announced promising first phase results from their first four patients. Faraz Ali of bluebird bio showed that his company has already made this life-changing shift for two patients with the blood disorder Beta Thalassemia. Like most patients with the disease they had been dependent on regular transfusions to survive, but when they received transplants of their own stem cells genetically modified to produce the correct version of a protein that is defective in the disease, they were able to live without transfusions.

The fourth panel provided proof that the field is maturing in that they discussed the many hurdles and pitfalls in taking those final steps to prepare a cell therapy to be a commercial product. The three big hurdles—financing, regulatory approval and reimbursement by insurers—all required creativity by the companies outlined in the two case studies. They are working through them but it is anything but a straightforward path. This is the area I hear the most hand wringing about in the halls of meetings in our field.

The last panel showed that one way around some of those end stage hurdles is to reach across borders. Four panelists discussed specific examples of ways international collaborations have accelerated their work toward developing therapies. CIRM has more than 20 collaborative agreements with funding agencies around the world, many of them painstakingly nurtured by our former president Alan Trounson. He gave the final presentation of the panel talking about one of his new projects, building an international stem cell bank with enough cell lines that almost everyone could get donor cells that were immunologically matched.

Our board chair, Jonathan Thomas, moderated the last panel and ended with a tribute to Alan noting that his build-out of our international program would be one of his many lasting legacies.
Don Gibbons

Stem Cell Stories that Caught our Eye: Speeding Stroke Recovery, HIV Clinical Trial, New Method for Growing Heart Cells

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.

Transplanting cells to speed stroke recovery. Stroke remains one of the most common forms of death and disability, yet utilization of therapies that can break down the blood clots that cause most forms of stroke lags; these therapies are only effective when used within 3 to 4 hours of the stroke but most patients arrive at the hospital too late. Now scientists from Shanghai Jiao Tong University may have a different solution that can repair damage already done.

Scientists have recently been looking to stem cell transplantation as a way to restore blood vessels or brain tissue destroyed by a stroke, but early experiments revealed limited effectiveness. In this study, which was published this week in Stem Cell Reports, the researchers coaxed embryonic stem cells further along in the development process before implanting them—which appears to have done the trick.

Using animal models, the team—led by Dr. Wei-Qiang Gao—transplanted two different types of so-called ‘precursor cells’ which have the ability to turn into the major types of brain and blood-vessel cells, the types of cells that are lost during a stroke.

Gao argues that this kind of transplantation is superior to previous methods because the two types of precursor cells can actually support each other in order to promote cell growth, and thus lays the foundation for new stem cell-based therapies to speed up recovery for stroke survivors.

CIRM-Funded Clinical Trial to Treat HIV. A team comprised of the City of Hope in Los Angeles, Sangamo Biosciences and the University of Southern California have developed an innovative approach to eradicating HIV.

With support from a CIRM grant, the researchers are developing a combination stem cell and gene therapy approach that is based on the success of the so-called “Berlin patient,” an HIV-positive man who was essentially cured after a bone-marrow transplant to treat his leukemia. In this instance, the bone marrow donor had a unique HIV-resistant mutation. The transplant transferred this mutation to the Berlin patient, and scientists have since been looking for a way to replicate this mutation on a larger scale. As explained in this week’s news release:

“Using an enzyme called a zinc-finger nuclease (ZFN), the research team can …“edit” the HIV patient’s stem cell genes so that, like the Berlin patient’s donor, they can no longer produce the protein. No protein, no HIV infection. The virus might then disappear from the body.

This study will be the first trial of ZFN technology in human stem cells. Earlier clinical studies in HIV-positive patients show that the ZFN method is generally safe when used with white blood cells called lymphocytes. And in one patient, the therapy was associated with temporary control of HIV without antiviral medication.”

The team hopes to begin testing this approach by the fall of 2014 on HIV patients who have not responded well to traditional therapies. CIRM funds a team that uses a different approach to gene editing that began a clinical trial last summer. You can read about both on our HIV fact sheet.

Building a Better Heart Cell. Stanford stem cell scientist Dr. Joseph Wu and his team have devised an improved method for generating large batches of heart muscle cells, known as cardiomyocytes, faster and cheaper than ever before. This new technique, described in the latest issue of Nature Methods, solves a long-standing problem in the field of regenerative medicine. As Wu explained in the Stanford University School of Medicine’s blog Scope:

“In order to fully realize the potential of these cells in drug screening and cell therapy, it’s necessary to be able to reliably generate large numbers at low cost….[Our] system is highly reproducible, massively scalable and substantially reduces costs to allow the production of billions of cardiomyocytes.”

This research, which was supported by a grant from CIRM, stands to improve scientists’ ability to use patient-derived cells not only to better understand how a heart becomes a heart, but also to test drugs that treat various types of heart disease.

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.”

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.”

Protein Drip Spurs Stem Cells to Save Heart Tissue

When you suffer a heart attack, beating heart muscle cells become deprived of oxygen and die—and become encased in scar tissue. Once these cells die, they can’t be brought back to life. But new research presented this week has found that injecting a protein into the heart immediately following an attack can spur stem cells to repair the damaged heart tissue.

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Presenting at this week’s Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting in St. Louis, MO, researchers from the Gunma Prefectural Cardiovascular Center in Maebashi, Japan, have found that a protein called G-CSF—when injected into the hearts of patients who recently suffered an attack—can actually spur a type of bone marrow stem cells to migrate to the heart and curb the spread of cellular death that normally takes place.

Previous research had revealed that administering G-CSF improves the heart’s ability to pump blood. In this study, the team wanted to understand how G-CSF could do so in a patient who just suffered a heart attack. Dr. Takuji Toyoma, the study’s lead author, explained in a news release:

“This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice.”

In this study, the researchers gathered 40 patients who had recently suffered an acute heart attack. They gave half of them an intravenous G-CSF for a period of five days, while the others received a saline solution. A year’s worth of imaging and stress tests then revealed that the earlier the G-CSF was administered, the greater the improvement in blood flow and overall cardiac function.

As Toyoma explained above, the next steps involve a forthcoming clinical trial where the precise effects of G-CSF, including the timing of when best to administer the protein, can be determined.

The research team’s preliminary efforts hold promise in the fight against heart disease. While heart disease is still the world’s number one killer, recent medical advances have increased the chances of surviving an attack. However, for those that do survive they often must live with heart failure—their hearts unable to beat at full capacity.

Many scientists, including a variety of researchers supported by CIRM, have therefore looked to regenerative medicine to regenerate lost heart muscle. The findings presented by Toyoma and his team point to another avenue by which stem cells could be harnessed to improve the quality of lives for those who have experienced a heart attack, and maybe prevent their slide into heart failure.

Protein Drip Spurs Stem Cells to Save Heart Tissue

When you suffer a heart attack, beating heart muscle cells become deprived of oxygen and die—and become encased in scar tissue. Once these cells die, they can’t be brought back to life. But new research presented this week has found that injecting a protein into the heart immediately following an attack can spur stem cells to repair the damaged heart tissue.

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Researchers have identified a protein that can mitigate the damage to cells caused by a heart attack

Presenting at this week’s Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting in St. Louis, MO, researchers from the Gunma Prefectural Cardiovascular Center in Maebashi, Japan, have found that a protein called G-CSF—when injected into the hearts of patients who recently suffered an attack—can actually spur a type of bone marrow stem cells to migrate to the heart and curb the spread of cellular death that normally takes place.

Previous research had revealed that administering G-CSF improves the heart’s ability to pump blood. In this study, the team wanted to understand how G-CSF could do so in a patient who just suffered a heart attack. Dr. Takuji Toyoma, the study’s lead author, explained in a news release:

“This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice.”

In this study, the researchers gathered 40 patients who had recently suffered an acute heart attack. They gave half of them an intravenous G-CSF for a period of five days, while the others received a saline solution. A year’s worth of imaging and stress tests then revealed that the earlier the G-CSF was administered, the greater the improvement in blood flow and overall cardiac function.

As Toyoma explained above, the next steps involve a forthcoming clinical trial where the precise effects of G-CSF, including the timing of when best to administer the protein, can be determined.

The research team’s preliminary efforts hold promise in the fight against heart disease. While heart disease is still the world’s number one killer, recent medical advances have increased the chances of surviving an attack. However, for those that do survive they often must live with heart failure—their hearts unable to beat at full capacity.

Many scientists, including a variety of researchers supported by CIRM, have therefore looked to regenerative medicine to regenerate lost heart muscle. The findings presented by Toyoma and his team point to another avenue by which stem cells could be harnessed to improve the quality of lives for those who have experienced a heart attack, and maybe prevent their slide into heart failure.