microRNA – New Kid On The Block Has Journalistic Baggage

“Duke University researchers used molecules called microRNAs to convert scar tissue (called fibroblasts) into heart muscle cells in a living mouse”

That’s great! Unfortunately, the author of the article foolishly decided to pit “microRNA – The New Kid On The Block” against the decade long reigning champ, Adult Stem Cells…and he needs to get his story straight.

New Kids On The Block

From the start, the author presents almost no accurate information about adult stem cells, their decade of history, successes, studies, trials, patients treated, safety, efficacy and potency.  He is incredibly dated on the understanding of adult stem cells and straight up wrong/ignorant on many of his points.  His original 3 point comparison is to Embryonic stem cells, already shown to be far inferior to Adult Stem Cells in every way including their potency.  He then states Adult Stem Cells have: “…a limited capacity to form other types of cells” which is completely wrong. 

He then quotes the Duke University doctor, ‘The results of using these adult stem cells for tissue regeneration are “not as satisfying as one would like.” 

• A. “not as satisfying as one would like.” is perhaps the most unscientific assessment I’ve ever heard 
• B.  I’m surprised to hear this from the doctor as Duke University has had tremendous success utilizing stem cells in treating pediatric Cerebral Palsy/Ataxia 
• C.  Would he be satisfied if there was a decade long history of cardiac tissue regeneration studies?  There is: http://repairstemcell.wordpress.com/heart-disease-treatment/
• D.  Would he be satisfied if you could grow an entire heart from scratch, from a patients’ own stem cells?  You can.

 

I suppose the author is not entirely to blame as the assertion within the peer reviewed article is completely erroneous as well: “this is the first report of direct cardiac reprogramming in vivo.”  Wrong!

I would further question whether microRNA cells are “smart” like adult stem cells are.  Gene therapy to turn heart muscle scar tissue into heart muscle is great but then you have a scar shaped piece of heart muscle.  Does it beat in perfect time with the rest of the heart muscle or is it asynchronous?  Can it grow an entirely new heart from scratch as adult stem cells can? (No, it can not)

An adult stem cell grows a cardiac cell from it’s proverbial birth and the cardiac cells conform from ‘birth’ and as they develop to the surrounding tissue and work in unison with the adjacent cells.  It would appear the microRNA transforms the scar tissue at a later stage of the cells growth.  This is then perhaps an “older cell” with it’s own inherent programming and limitations. Prone to it’s own agenda, these doppelganger heart cells may cause conflicts with the existing cells and the rest of the heart muscle.

Just changing scar to muscle is only a fraction of what stem cells can do.  “Smart” adult stem cells will build the cells needed, put them in the places they are needed, create valves where valves are needed, capillaries if those are needed, bring dead heart tissue back to life and then some will migrate down to the pancreas and heal that as well.

microRNA gene therapy may have a long future of success and I am sure there are some applications which they will be great.  To compare them to adult stem cells in the context of regenerative medicine as the author has done, especially without a proper understanding of the safety and efficacy record of adult stem cells, especially in the field of cardiac regenerative medicine which has a decade long history (the longest of all practical and clinical research), is like bringing a rubber knife to a gun fight.

Repairing the heart without using stem cells

By Alex Crees Published April 27, 2012 FoxNews.com

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When a person suffers a heart attack, scar tissue forms over the damaged areas of the heart, reducing the organ’s function.  However, in a recent study, scientists successfully turned this scar tissue into working heart muscle without the use of stem cells.

Duke University researchers used molecules called microRNAs to convert scar tissue (called fibroblasts) into heart muscle cells in a living mouse, improving the heart’s ability to pump blood.

According to the scientists, this process is much simpler than stem cell transplants and has none of the ethical concerns, making it a potential turning point in the science of tissue regeneration.

“Right now, there’s no good evidence stem cells can do the job,” senior author Dr. Victor Dzau, a James B. Duke professor of medicine and chancellor of health affairs at Duke University, told FoxNews.com.

Scientists believe embryonic stem cells are the best to use for tissue regeneration because they are pluripotent—meaning they can become any type of cell in the body.  However, Dzau said there have not been enough experiments done to prove how functional the stem cells are in regenerating tissues and whether or not they may form deadly tumors.

Additionally, there are ethical concerns about using cells derived from a human embryo, he said.

Meanwhile, adult stem cells avoid the controversy surrounding embryonic stem cells but have a limited capacity to form other types of cells.  The results of using these adult stem cells for tissue regeneration are “not as satisfying as one would like,” Dzau said.

Rather than stem cells, the new method developed by Dzau’s team uses microRNA molecules—which typically control gene activity—and delivers them into the scar tissue that develops after a heart attack.  The microRNAs are able to reprogram, or trick, the scar tissue into becoming heart muscle again instead.

Testing is still in its early stages, but so far, the method appears to be relatively easy, and the data looks very promising, according to the researchers.

“It’s a much simplified, feasible way of causing regeneration; very easy to use as therapy,” Dzau said.  “With stem cells, you have to take them from the embryo or tissue in the body, grow them in culture, and re-inject them—and then there can be technical and biological problems.

“With microRNA, after a heart attack you can simply convert some of the fibroblasts and tell them to become the right cell type and regenerate,” he said.

The method also has the potential to treat stroke, spinal cord injuries, chronic conditions such as heart disease—and even the normal damage that can come with aging.  It can feasibly be used for any type of organ in the body, though the process of converting the cells may be different for each organ.

“Right now, our work is proof of concept,” Dzau said, adding that the method must still be tested in then larger animals, and if successful there, it can move onto human clinical trials.  “But one could think about all these things of possibilities.  Could you use it to treat the disease of aging and losing brain cells?  Can you convert other cells in the brain to working brain cells?

“It’s a significant finding because it changes the way we think about regenerating tissues,” Dzau said.  “It breaks open a whole new area.”

The study was funded in part by the National Heart, Lung and Blood Institute and published Thursday in the journal Circulation Research.

NEW STEM CELL FOUND IN THE BRAIN

Researchers at Lund University have discovered a new stem cell in the adult brain. These cells can proliferate and form several different cell types – most importantly, they can form new brain cells. Now the researchers hope to put the discovery to use to develop methods that can repair diseases and injury to the brain.

Analysing brain tissue from biopsies, the researchers for the first time found stem cells located around small blood vessels in the brain. The cell’s specific function is still unclear, but its plastic properties suggest great potential. A similar cell type has been identified in several other organs where it can promote regeneration of muscle, bone, cartilage and adipose tissue.

In other organs, researchers have shown clear evidence that these types of cells contribute to repair and wound healing. Scientists suggest that the curative properties may also apply to the brain. The next step is to try to control and enhance stem cell self-healing properties with the aim of carrying out therapies targeted to a specific area of the brain.

“Our findings show that the cell capacity is much larger than we originally thought, and that these cells are very versatile,” said Gesine Paul-Visse, Ph.D., Associate Professor of Neuroscience at Lund University.

“Most interesting is their ability to form neuronal cells, but they can also be developed for other cell types. The results contribute to better understanding of how brain cell plasticity works and opens up new opportunities to exploit these very features.”

The study, published in the journal PLoS ONE, is of interest to a broad spectrum of brain research. Future possible therapeutic targets range from neurodegenerative diseases to stroke.

“We hope that our findings may lead to a new and better understanding of the brain’s own repair mechanisms,” said Dr. Paul-Visse. “Ultimately the goal is to strengthen these mechanisms and develop new treatments that can repair the diseased brain.”

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Link to the study here:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035577

The study:

Title: The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells Published in: PLoS ONE, 16 April, 2012.

New stem cell found in the brain.

MAKING SENSE OF THE FDA AND STEM CELLS – WSJ OPED

By ANDREW VON ESCHENBACH-WSJ 4/15/12-See
http://online.wsj.com/articleSB10001424052702303815404577331673917964962.html?mod=googlen
ews_wsj

When I was commissioner of the Food and Drug Administration (FDA) from 2005 to 2009, I saw firsthand how regenerative medicine offered a cure for kidney and heart failure and other chronic conditions like diabetes. Researchers used stem cells to grow cells and tissues to replace failing organs, eliminating the need for expensive supportive treatments like dialysis and organ transplants.

But the beneficiaries were laboratory animals. Breakthroughs for humans were and still are a long way off. They have been stalled by regulatory uncertainty, because the FDA doesn’t have the scientific tools and resources to review complex innovations more expeditiously and pioneer regulatory pathways for state-of-the-art therapies that defy current agency conventions. Fortunately, Congress may have an opportunity as soon as this week to begin changing that.

The FDA isn’t obstructing progress because its employees are mean-spirited or foolish. But for decades, Congress has starved the agency of critical funding, limiting its scientists’ ability to keep up with peers in private industry and academia. The result is an agency in which science-based regulation often lags far behind scientific discovery. This forces the FDA to slow the approval of new treatments—and at times
creates acrimonious litigation between the FDA and innovators, not to mention disillusionment among desperate patients.

For example, in August 2010, the FDA filed suit against a company called Regenerative Sciences. Three years earlier, the company had begun marketing a process it called Regenexx to repair damaged joints by injecting them with a patient’s own stem cells. The FDA alleged that the cells the firm used had been manipulated to the point that they should be regulated as drugs. A resulting court injunction halting use of the technique has cast a pall over the future of regenerative medicine.

From the agency’s perspective, it had only called a “time out” until it could apply its regulatory process designed to analyze the therapy’s effectiveness and potential risks. For the industry, however, government had intervened in a way that seemed to bar the established clinical practice of using an individual’s own cells to advance the healing process.

Lawyers—many lawyers—are now trying to resolve this dispute. But at a time when science and technology are creating marvelous medical breakthroughs, the FDA should be leading and guiding the development of state-of-the-art therapies like regenerative medicine. Instead, the agency’s process for regulating complex new technologies often starts too late, after companies and researchers have sunk millions of dollars and thousands of hours into painstaking research.

It makes far better sense for the FDA to work collaboratively with physicians, patients, companies and academic researchers to craft standards for evaluating new technologies while they are still being developed, not years later when a company makes a marketing application for a breakthrough product.

Until that time, FDA scientists typically have little contact with the scientists who know the most about these innovative technologies.

This is not because they don’t want to. But consumer groups distrustful of industry have led Congress to erect ever greater barriers between regulators and those they regulate. The FDA can convene advisory committees of outside experts, but these experts weigh in only at the end of the regulatory process.

Worse, congressionally mandated conflict-of-interest rules keep many of the most knowledgeable academic and industry scientists off advisory committees out of fear that industry ties might bias their judgment.

Meanwhile, budget constraints have eroded the agency’s scientific foundations. When I moved from director of the National Cancer Institute at the National Institutes of Health (NIH) to become FDA commissioner in 2005, I was surprised to learn there are no provisions for continuous education to acquire new skills in emerging fields such as stem-cell biology, nanotechnology or computational biology. Even sending agency staff to academic conferences provoked a congressional outcry over meeting and travel costs.

If we want the FDA to lead innovation, and not lag behind it, Congress must give the agency the resources to be the world’s foremost science-based regulatory agency. It should endorse formal career development programs and encourage more collaboration with scientists in academia, industry, NIH and other federal agencies.

Congress should also make conflict-of-interest restrictions more rational, to ensure that agency staff can get early access to external scientific expertise to evaluate emerging technologies. The FDA should be able to make greater use of scientific consultants as “Special Government Employees” to broaden the pool of qualified and approved advisers for the agency.

FDA scientists I have encountered do care deeply about patients and want to say “yes” to safe and effective new therapies. Regulatory approval is the only bridge between miracles in the laboratory and lifesaving treatments. Yet until FDA reviewers can be scientifically confident of the benefits and risks of a new technology, their duty is to stop it—and stop it they will.

Congress has an opportunity to improve all this as it considers renewing FDA user-fee legislation this year. The temptation will be to reauthorize the fees as quickly as possible and move on as usual for another five years. This would be a grave mistake. Reforms that allow the FDA to say “yes” to innovative therapies serve all the agency’s stakeholders, including current and future patients.

Otherwise we had better get used to the agency saying no by calling “time out” or, worse, “game over” for American companies developing new, vital technologies like regenerative medicine.

Dr. von Eschenbach, a former director of the National Cancer Institute and commissioner of the Food and Drug Administration from 2006 to 2009, is chairman of the Manhattan Institute’s Project FDA.