Month Archives: August 2011

Immature Cells Result from Embryonic Stem Cells

by David Prentice

August 18, 2011

Like an out of control youth, embryonic stem cells can wreak havoc with tissue damage and tumor formation. Their inability to make appropriate, mature cells that can function in an adult body is also a problem. Scientists at UCLA have found that cells derived from pluripotent stem cells are developmentally very immature, and do not resemble the adult cell types that they would theoretically replace in a transplant. The immaturity was seen in cell derivatives from both embryonic stem cells and induced pluripotent stem (iPS) cells. The data indicate that pluripotent stem cells such as embryonic stem cells are inappropriate substitutes for adult stem cells in patient treatments.

One goal of the UCLA study was to address the ongoing question of just how closely iPS cells resemble embryonic stem cells. The researchers derived several different cell types from both human embryonic stem cells and human iPS cells—neuronal cells, hepatocytes (liver cells), and fibroblasts (common in skin and connective tissue.) The progeny of the human pluripotent stem cells were compared to each other by gene expression patterns, functionality and appearance. The authors noted that the two cell types “make nearly identical progeny”, with essentially no difference between them, again indicating that iPS cells can substitute for embryonic stem cells in laboratory studies.

But when the scientists compared the cells made from pluripotent stem cells to normal human tissue cells, there were significant differences in gene expression patterns. Cells made from embryonic stem cells and iPS cells had not turned off many of the genes normally expressed only in growing, pluripotent stem cells. According to senior author Dr. William Lowry, this could be very problematic, since some of those same pluripotency genes are expressed during cancer development. The cells derived from embryonic stem cells were developmentally very immature, and were most similar to cells less than six weeks after conception, in the earliest stages of human development. Lowry said:

What we found, looking at gene expression, was that the cells we derived were similar to cells found in early fetal development and were functionally much more immature than cells taken from human tissue. This finding may lead to exciting new ways to study early human development, but it also may present a challenge for transplantation, because the cells you end up with are not something that’s indicative of a cell you’d find in an adult or even in a newborn baby.”

Other groups have previously documented similar results, that embryonic stem cells produce immature cells, and that embryonic stem cell derivatives are inappropriate for use in transplants. This new study published in the journal Cell Research shows the developmental level to be very immature. These are critical discrepancies that could be lethal during transplantation, again indicating that embryonic stem cell derivatives are inappropriate for therapies.

Meanwhile, adult stem cells continue to treat over 50,000 patients a year around the globe.

Adult stem cells remain the gold standard for actual patient treatments.

Getting an Ear Full of Adult Stem Cells

by David Prentice

August 17, 2011

Japanese scientists have shown that useful adult stem cells can be isolated from the human ear. The cells come from a part of the ear called the perichondrium, which is a thin layer of connective tissue that covers and protects cartilage in the human body. Previously another group had shown the regenerative potential of adult stem cells from rabbit ears, but the new study is the first to show such adult stem cells present in the human ear.

Prof. Shinji Kobayashi, lead author on the study published in the Proceedings of the National Academy of Sciences, and his colleagues discovered adult stem cells from the membrane that covers cartilage in the human ear. They developed a technique to grow the adult stem cells into cartilage efficiently, and found that the human stem cell-derived cartilage was stable for at least 10 months after it was transplanted under the skin of mice.

As the authors note in their published paper, there is great demand for effective treatments for craniofacial injuries or abnormalities, but effective treatments are currently lacking. Their discovery of this new, easily-accessible source of adult stem cells and their technique for efficient growth of cartilage would allow patients suffering from craniofacial deformities to be treated with reconstructive material grown from adult stem cells collected from their own ears. The scientists hope to start a clinical study as early as 2012.

Moon Race

by Robert Morrison

August 17, 2011

During a recent family move, my wife and I had the pleasure of helping our son-in-law and daughter pack out in their new digs. While my wife and daughter rushed to put away all towels and sheets and our handy son-in-law put the lawn mower back together, I got the plumb assignment: I was to read and occupy our two-year old grandson.

As soon as the movers dropped the couch in the living room, I opened the special book Id brought for this occasion. MOON LANDING is the story of Americas victory in the race to the Moon in 1969. Astronaut Buzz Aldrin wrote the text, but its specially made for boys. Its a pop-up book. Everything from the Redstone rocket that began Americas mission to space to the Lunar Landerthe famed Eagle that first touched the surface of the Moon on July 19, 1969was shown in three dimensions. Its a wonderful book, the kind of book I wish Id had when I was a boy—a boy of eight.

My wife and daughter were tolerant of my enthusiasm. Eight and Above was clearly written below the title of the book. Wasnt I stretching it a bit? Our grandson sat quietly on the couch as I read him the book, but did not respond.

I had personal reasons for sharing the Moon with him. Years ago, I was assigned by Gary Bauer, then the president of Family Research Council, to analyze the National History Standards. That was a 214-page volume of everything American high school students need to know about their countrys history. Some three hundred history professors and high school teachers had labored for several years to compile the NHS.

When it was released, however, a storm of protest arose. Lynn Cheney, the wife of Dick Cheney, and the former head of the National Endowment for the Humanities, protested.

She was sorry she had launched the project, she wrote. She was appalled at the dark and negative picture the NHS experts had portrayed. Columnist George Will skewered the 214-page tome as anti-American history standards.

Gary Bauer cares a lot aboutU.S.history and education. He wanted FRC to weigh in.

Find out whats good, whats bad, and whats missing,Garyinstructed me. He didnt add that it had better be quick.

With the able assistance of two bright young interns, Jennifer Marshall and Scott Sonju, and a Lexington, Mass., school teacher, Eric Unsworth, we pored over the National History Standards. Whats good. Whats bad. Not so hard to determine. But whats missing? Not so easy.

Suddenly, at 2 am, I awoke with a start. What about the Moon Landing? What did these 300 history experts say about the U.S. Landing on the Moon? I raced into the office next morning and seized the volume. I couldnt find it.

The NHS listed Soviet gains in space in the 1960s. Well, OK. But only until 1965. It listed the Challenger disaster of 1986, but failed to note President Reagans moving address to the nation that very night:

We will never forget them, nor the last time we saw them, this morning, as they prepared for their journey and waved good-bye and slipped the surly bonds of earth to touch the face of God.

The 300 experts who compiled the list of what every American should know completely omitted any reference to the U.S. Landing on the Moon. They might as well have joined that little cult that thinks the whole thing was faked on a back lot in Hollywood.

This was a stunning omission. Gary Bauer laughed. So did the rest ofFRCs small staff. We raced into print with a full-page ad ribbing the mostly liberal crew of historians:

They Promised Us the MoonBut they missed it.

Those historians are the kind of folks who today dismiss Thomas Jefferson simply as a slaveholder and regale students with stories of George Washingtons false teeth.

The U.S. Landing on the Moon was an epochal event. It was the fruition of young John F. Kennedys bold gamble. In the last speech of his life, he said Americahas thrown its cap over the wall of space as he bade us go after it. The night that Astronaut Neil Armstrong took one small step for man, one giant leap for mankind someone put flowers on President Kennedys grave atArlingtonwith this note: The Eagle has landed.

All this drama they had left out. Why? The picture those experts painted of America was so grim, such a record of injustice and oppression, youd think wed have to put up a fence along the Rio Grande—to keep suffering Americans in.

I didnt expect to unload all of this on my grandson. Last week, however, his parents took him for a ride around their new neighborhood on his tricycle. A full moon came out.

He pointed at it and said: Mans walk on the Moon. Hes working on his plurals.

We need to re-kindle that excitement and awe. We need to give the rising generation a sense of infinite possibilities. Our reach should exceed our grasp, else whats a Heaven for?

Human Experiments as Creepy or Ethical?

by David Prentice

August 17, 2011

Greg Pollowitz over at National Review Online has a brief post about a disturbing article at Wired; Pollowitz titles his post “Josef Mengele Now Writing for Wired Magazine?” Before you condemn that as harsh, check out the article mentioned, titled “Seven Creepy Experiments That Could Teach Us So Much (If They Werent So Wrong)” and decide for yourself if these proposals are creepy, or even if you consider them wrong. Perhaps what is really creepy, as well as sad, is that some supposedly serious scientists don’t really consider these or other equally disturbing proposals unethical or creepy, but simply “interesting science”, even worth pursuing for the greater good, or holding great potential for scientific or medical breakthroughs and cures (the most common justification). The question really is, what makes these proposed experiments so wrong? Is it because these are experiments on human beings, that manipulate humans? Is any human life valuable, are all humans valuable? Worth pondering in terms of what we deem wrong or unethical.

Mobilized Adult Stem Cell Procedure Shown Safe for Donors

by David Prentice

August 17, 2011

A study by University of Minnesota Medical School researchers shows that mobilizing adult stem cells from bone marrow is safe for the adult stem cell donors. Many people are familiar with “bone marrow transplants”, which are actually “adult stem cell transplants”, though it wasn’t until the 1990’s that the first human adult stem cell was successfully isolated and purified. Bone marrow adult stem cell donors provide a lifesaving donation of cells for people with various cancers, anemias, and a growing number of other conditions. Collecting the lifesaving adult stem cells directly from bone marrow is a surgical outpatient procedure. But the adult stem cells can also be collected from peripheral blood. Donors can be given a protein growth factor/drug called granulocyte colonystimulating factor (GCSF; also called filgrastim or Neupogen). This stimulates adult stem cells to move out of the bone marrow and into the blood stream, a process called mobilization. Once in the blood, large doses of adult stem cells can be collected safely and without surgery by a process called apheresis, avoiding bone marrow harvest in the operating room.

Since 2003, over 70% of “bone marrow” or “stem cell” donors have been asked to donate mobilized cells from peripheral blood (Peripheral Blood Stem Cells, PBSC.). Donor adult stem cells are used in a little less than half of the over 50,000 adult stem cell transplants done every year. Previously, there had been some concern that high doses of G-CSF given to donors might result in abnormalities in donors’ cells.

The current study, which was published in the journal Blood, shows that it is unlikely that the mobilization procedure puts healthy stem cell donors at risk for later development of cell abnormalities. Dr. Jeffrey McCullough, senior author on the study, said:

Furthermore, our data support the conclusion that GCSF does not induce chromosomal instability through the PBSC mobilization process and remains a safe therapy for healthy stem cell donors.”

Adult stem cells remain the gold standard for actual patient treatments.

Coffee and Chocolate to Prevent Sunburn

by David Prentice

August 17, 2011

Two basic food groups—caffeine and chocolate—may also be useful in preventing sunburn.

Rutgers scientists have published evidence that caffeine guards against certain skin cancers by inhibiting a protein enzyme in the skin, known as ATR. They believe that it might be feasible to apply caffeine directly to the skin to help prevent damaging UV light from causing skin cancer.

In a separate announcement, Canadian scientists said they will begin a study to determine whether chocolate can prevent sunburn. Previous research in Germany and Britain found that chemicals in chocolate called polyphenols increase blood flow close to the skin, which helps protect against ultraviolet rays, but those studies were too small in scale to be conclusive. The new study will enlist larger numbers of volunteers, who will be fed chocolate and then exposed to UV light in a laboratory, and their skin then checked for sun damage. A control group will be given a placebo. I’d hate to be in the control group and get fake chocolate.

Scientists Try to Decrease Dangerous Tumors from Embryonic Stem Cells

by David Prentice

August 17, 2011

Stanford scientists have published a report in which they tried to decrease the tumor propensity of embryonic stem cells. One of the chief characteristics of embryonic stem cells is that they like to grow—and grow, and grow, often leading to tumors. Previous research has shown that as few as two growing embryonic stem cells among millions of injected cells can lead to tumors, even if the cells are supposedly pre-differentiated.

In trying to get around the inherent danger of embryonic stem cells, the scientists developed an antibody against a previously unidentified antigen (stage-specific embryonic antigen-5, or SSEA-5) that is highly and specifically expressed on all human pluripotent stem cells—embryonic stem cells which require destruction of young human life, and induced pluripotent stem cells (iPS cells) that are produced by adding genes to normal skin cells, without the use of embryos, eggs, or cloning.

Their hope was that the antibody could be used to identify and separate the lethal tumor-causing cells from a population of embryonic stem cells. The anit-SSEA-5 bound to embryonic stem cells, as well as to the inner cell mass of early human embryos, the group of cells from which embryonic stem cell lines are derived after destruction of the embryo. Their next step was to try to use the antibody to remove tumor-forming cells from cultures of embryonic stem cells. According to senior author Micha Drukker:

Commonly used differentiation protocols for embryonic stem and iPS cells often give rise to mixed cultures of cells. Because even a single undifferentiated cell harbors the ability to become a teratoma, we sought to develop a way to remove these cells before transplantation.”

When the scientists injected human embryonic stem cells recognized by the anti-SSEA-5 antibody into mice, rapidly-growing tumors formed in 7 out of 7 mice injected. When they injected cells that were not recognized by the anti-SSEA-5 antibody, tumors formed in 3 of 11 mice injected. Combining the anti-SSEA-5 antibody with two other commercial antibodies decreased tumor growth, although they did see some smaller, less-diverse tumorous growths. The authors also only measured the incidence of tumors detected after the relatively short time of 912 weeks; longer periods of time would be required to see all tumors that arise from the embryonic stem cells.

First author Chad Tang noted that this was a “proof of concept” study, and that different combinations of antibodies may be required for embryonic stem cell cultures developing into different types of cells. It’s also unlikely that the antibody technique would remove cells that had ceased growing and were supposedly differentiated, but resumed growth later. Certainly these results from a single small study will need to be confirmed with published data from other labs.

Stanford University has filed for patent protection for the use of these monoclonal antibody-based protocols to remove tumor-forming pluripotent stem cells from a cell mixture.

Two companies have begun experiments with patients, injecting embryonic stem cell derivatives into eyes and into spinal cords. It’s far too early to tell whether any tumor problems may develop, though at least one of the companies has promised to follow patients for 15 years because of the tumor concerns inherent with embryonic stem cells. The fact that neither ACT nor Geron provided definitive published proof that they can control tumor formation is a significant concern, even among proponents of embryonic stem cells.

Direct Conversion of Skin to Nerve and Other Tissues, Without Stem Cells

by David Prentice

August 17, 2011

(part of this information was originally posted at Lifenews.com)

A passel of scientific papers have recently reported the direct conversion of skin cells to nerve cells, without going through an intervening stem cell step.

You’ve Got a Lot of Nerve

No fewer than seven studies published in the last three months have shown different methods for directly converting ordinary skin cells into types of nerve cells.

The direct conversion technique, also called direct reprogramming, builds on the reprogramming work of Dr. Shinya Yamanaka. In 2006, Dr. Yamanaka announced his groundbreaking technique of adding four genes to a normal cell, reprogramming it to act like an embryonic stem cell, yet without use of embryos, eggs, or cloning. The newly-reprogrammed stem cell, termed an induced pluripotent stem cell (iPS cell), was first developed in mice, and then the same technique was shown to work with human cells in 2007. Yamanaka’s iPS cell method bypasses the ethical problems of embryonic stem cells. However, the iPS cells still need to be differentiated into specialized cell types for tissues, and still show the same practical problems of a tendency to form tumors, as seen with embryonic stem cells.

The even newer technique of direct conversion skips the stem cell intermediary, directly transforming one specialized cell type into another specialized cell type.

In late July, researchers at the Gladstone Institute led by Dr. Sheng Ding published details of an efficient method to turn human adult skin cells directly into functional brain cells. The technique, published in the journal Cell Stem Cell, uses two specific genes in combination with a small strand of genetic material called a microRNA; adding the three components to normal human skin cells converts the cells into nerve cells. The newly-formed nerve cells are functional, able to fire signals and form connections with other nerve cells.

An earlier publication by this group in May showed that mouse fibroblasts could be directly converted to neural stem cells, using a transient treatment with Yamanaka gene factors. The brief exposure to the gene factors produced neural stem cells that could be grown further in numbers in cell culture and then specialized to various types of nerve cells.

In early August, a collaboration of New York scientists showed that they could directly convert skin cells from Alzheimer’s patients into neurons, bypassing stem cells. The process they developed, published in the journal Cell, uses a set of three-five genes normally expressed in brain; the genes were introduced into fibroblast cells (generic connective tissue and skin cells) and the cells were grown in the presence of nerve-stimulatory factors. Within three weeks, the skin cells looked and acted like neuronal cells. When made from normal healthy adult skin cells, the new nerve cells could send and receive signals, just like normal neurons. Furthermore, when placed into the brains of developing mice, the converted nerve cells were able to connect with the existing nervous system circuitry. The researchers also converted skin cells from Alzheimer’s disease patients into nerve cells, and observed abnormalities in the converted nerve cells similar to those seen in Alzheimer’s brain cells. They hope to use the converted cells to study details of the disease and potentially to test therapeutic drugs.

In mid-August, the journal Nature published three separate papers describing methods for direct conversion of normal skin cells into nerve cells.

In one paper (Pang et al.), a group of Stanford researchers showed that forced expression of three-four genes could directly convert human iPS cells and human skin cells into functioning nerve cells, complete with functional connections to other nerve cells. They note that their method may provide patient-specific human neurons for lab-based modeling of disease and possibly future applications in regenerative medicine.” The paper had been previously published online in May.

A second group of Stanford scientists (Yoo et al.) took a different route, showing that small molecules called microRNA could nudge human skin cells into become neurons. While microRNA usually is involved in turning off expression of specific genes in a cell, in this case two specific microRNA molecules were sufficient to convince human skin cells to turn directly into nerve cells, and the efficiency could be enhanced by adding a few other genes associated with nerve development.

A third paper (Caiazzo et al.) published by an Italian group showed that mouse as well as human skin cells could be directly converted to functional dopaminergic neurons, using expression of three specific nerve-associated genes. Dopaminergic neurons are the type of nerves lost during Parkinson’s disease. The researchers found that they could produce this type of nerve from both healthy donors and Parkinsons disease patients. The technique could have significance for studying Parkinson’s disease in the laboratory, as well as possible treatments.

Similar results were reported by a Swedish group in June. They found that they could directly convert human fibroblasts into nerve cells by adding three genes normally associated with nerves, and could specifically produce dopaminergic neurons by including two specific additional genes. Research leader Dr. Malin Parmar said he was surprised at how receptive the fibroblasts were to new instructions:

We didn’t really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions.”

The Swedish team noted that using the direct conversion technique to bypass stem cells avoided the ethical problems inherent with embryonic stem cells, as well as the tendency of embryonic stem cells to form tumors. The paper was published in the journal Proceedings of the National Academy of Sciences.

You’ve Got Heart, and Liver too

Beyond all the papers aimed at forming nerve cells, there have been a few other papers using the direct conversion technique to form other tissues as well.

In July, researchers at the University of Pennsylvania converted brain cells and skin cells into heart cells. As they detailed in the paper published in the Proceedings of the National Academy of Sciences, they injected messenger RNAs (mRNAs) extracted from heart cells into brain astrocytes or fibroblast cells, which resulted in direct conversion of the cells into heart cells (cardiomyocytes), without any stem cell intermediate.

Earlier in the year, the Sheng Ding laboratory published a different method for directly converting mouse skin cells into cardiomyocytes, essentially by short-circuiting the usual reprogramming strategy used to make iPS cells. The technique used the standard set of four genes usually used to make iPS cells, but cut short the exposure time and then placed the cells in conditions conducive to heart cell formation.

In July, Japanese researchers showed that specific combinations of transcription factors that control gene expression can convert mouse fibroblasts into hepatocytes (liver cells) in the lab. Not only did the converted cells resemble liver cells when examined in the laboratory, but they also could form mature liver cells and repair liver damage when transplanted into mice.

Previously, direct conversion had been used to make human blood cells, as well as mouse neurons, cardiomyocytes, and insulin-secreting cells.

The direct conversion technique provides a powerful, yet ethical, technique to produce various specialized cells in the lab.

Adult stem cells remain the gold standard for actual patient treatments.

This Little Light of Mine Stimulates Heart Repair by Adult Stem Cells

by David Prentice

August 17, 2011

Numerous previous studies have shown that adult stem cells can facilitate repair of damaged heart muscle. Now an Israeli team has developed a method to stimulate bone marrow adult stem cells to increase their ability to help restore heart function.

The new method uses laser-treated bone marrow adult stem cells to help restore heart function. The technique using low-level laser light is called “shining”. In the mouse study to show the technique’s effectiveness, the team shone laser light directly on bone marrow, and then tracked the bone marrow adult stem cells and the repair of the mouse hearts after treatment. They found that when the laser light was applied to bone marrow cells a few hours after a heart attack, heart scarring could be reduced by up to 80 percent. Mice that received the shining treatment also showed a significantly higher concentration of adult stem cells in the injured heart compared to mice that had not been treated with the laser light.

According to senior author Prof. Uri Oron:

After we stimulate the cells with the laser and enhance their proliferation in the bone marrow, it’s likely that more cells will migrate into the bloodstream. The cells that eventually reach the heart secrete growth factors to a higher extent, and new blood vessel formation is encouraged.”

Prof. Oron sees this as a way to make cell therapy simpler. Since there is no need to remove stem cells from the body, this treatment stimulates a whole variety of stem cells to help heal the body. Prof. Oron believes this method could also be beneficial for repair of other organs such as the kidney or the liver. He and his colleagues have also done a series of studies to show that the technique is safe, and are ready to begin clinical trials soon.

The study was recently reported in the journal Lasers in Surgery and Medicine.

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