[An original, shorter version of this post first appeared at Lifenews.com!]

Turning a blind eye toward both good science and good ethics, the embryonic stem cell and cloning company, Advanced Cell Technology (ACT), has published a very preliminary online report regarding their first two patients injected with embryonic stem cell derivatives. The two patients, one who has age-related macular degeneration, the most common cause of blindness, and the other with a rare form of blindness called Stargardt’s disease, were injected with retinal cells made from human embryonic stem cells only 4 months before the report was submitted. This makes it far too early to know whether these embryonic stem cells will actually be safe or effective. In fact, it’s surprising that any reputable scientific journal would publish such very preliminary data, given the early stage of the clinical trial (which is supposed to last at least two years), the short period of time after the patients were injected, and the low numbers of patients and lack of controls.

Dr Martin Friedlander, Professor of Ophthalmology at Scripps Health in La Jolla, California pointed out the deficits and dangers of such early and incomplete reporting:

“To reach any conclusions on the safety or efficacy of two patients treated for four months without a control population for comparison is unreasonable. This is why anecdotal reports like this are not published. This falsely raises the hopes of millions of individuals suffering from these diseases.”

The paper published in the journal Lancet clearly reveals that the data are preliminary and uncertain. It mentions that one patient who showed improvement in her eye that was injected with the cells, also showed improvement in her eye that was NOT injected with the cells. The authors admit in the paper that there is a general lack of hard data:

“At present, we do not know if the transplanted cells have reduced immunogenicity or whether they will undergo rejection without immunosuppression in the long term. Similarly, we are uncertain at this point whether any of the visual gains we have recorded were due to the transplanted cells, the use of immunosuppressive drugs, or a placebo effect.”

First author Dr. Steven Schwartz has noted the likelihood of the placebo effect in several interviews. Dr. Schwartz conceded that it was “extremely unusual” for researchers to publish a study after treating only two patients out of a planned 24. But he said that was justified by the huge interest in the stem cells. ACT has been criticized in the past for overstating results, in part because it has been desperate to raise money to stay in business. The company’s stock rose 3.4 cents, or 23 percent, to 18 cents on Monday.

The safety of the patients is also still very much in question. Humans can take much longer to develop a tumor than lab mice, sometimes years. 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. The concern regarding potential tumor formation and need for continued surveillance was noted by Dr. Sheng Ding of the Gladstone Institute:

If just a few undifferentiated stem cells are injected, “you may not see [an effect] at all, or you may be able to see it over a much longer period of time. The 4-month follow-up received by the trial patients thus far is “very short in this regard, and I think the patients need a much, much longer-term follow up to make sure there’s no tumor cells.”

It is indeed surprising that this paper was published. The preliminary nature of the paper reinforces the image of ACT noted in a recent story in Nature:

“Since the late 1990s, ACT has gained a reputation as a renegade company, accused of overhyping results to raise attention and money. Critics say that the company has damaged the field more than once with its high-profile, controversial announcements, such as one describing the company’s attempts to clone a human embryo in 2001…”

The embryonic stem cells (line MA09, currently pending review for NIH approval of taxpayer funding) used for injections into patients in the current trials are part of another embarrassing moment for ACT. Their derivation was described in a 2006 paper in which ACT claimed that they arose from single blastomeres that had been removed from human embryos, without destroying the embryos. However, the embryos had indeed been destroyed cell by cell, leading to several “corrections” to their published information. In a subsequent 2008 paper they again claimed to have accomplished derivation of embryonic stem cells without destroying an embryo, creating what they termed their NED (“no embryo destruction”) lines, but their own published data showed only 80-85% of the embryos survived the laboratory manipulation, falsifying their claim.

There are certainly better alternatives to embryonic stem cells. Similar stem cells–iPS cells–can be derived without any use of embryos; their potential is noted in the accompanying published comment. In fact, ACT scientist Bob Lanza has already said that they are planning to use iPS cells in the future, which potentially could remove the need for immunosuppressive drugs and provide an ethically-derived source of cells. However, since iPS cells are pluripotent, with a penchant to grow and make lots of cells, they face the same practical problem of tumor formation as embryonic stem cells.

A practical, as well as ethical solution, would be the use of adult stem cells. Preliminary work has shown that retinal repair could be accomplished using adult stem cells from bone marrow, or possibly even adult stem cells from within the patient’s own eye. Adult stem cells from the patient’s own eye have already been used successfully to treat corneal blindness in people.

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A couple of weeks ago a paper was published in Nature Communications, describing how scientists at the University of Pittsburgh School of Medicine have shown that adult stem cells from the muscle of young mice can improve the health and extend the life of aged mice. While the story didn’t make big news at the time, the news is surfacing again, e.g., in a video report by Dr. Marc Siegel on Fox News. The video includes interviews with two of the scientists who did the study, Dr. Laura Niedernhofer and Dr. Johnny Huard. Dr. Siegel does a good job of discussing the key points of the study, including the point that these were not embryonic stem cells, but rather adult stem cells.

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Nature notes that the first brief has been filed in the appeal of the Sherley et al. v. Sebelius et al. case. Dr. James Sherley and Dr. Theresa Deisher have filed suit against HHS and NIH to stop federal taxpayer funding of human embryonic stem cell research. The initial appeals brief (Appellants’ Brief) was filed by attorneys for Drs. Sherley and Deisher.

The briefing schedule was set back in December, as well as the date for oral arguments in the appeal.

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A 30-year-old Baltimore man is now back home recuperating from surgery in Sweden that implanted an artificial trachea made with his own adult stem cells. Christopher Lyles was diagnosed with inoperable tracheal cancer. He found Italian Dr. Paolo Macchiarini, who is a Visiting Professor at the Karolinska Institute in Stockholm, Sweden, who has constructed and transplanted replacement tracheas, using the patient’s own bone marrow adult stem cells to build the new tissue. Lyles traveled to Sweden in November to have the surgery; he returned home this week with his new implanted trachea. In a telephone interview, Lyles said he was “feeling good”, and “just thankful for a second chance at life.” He was looking forward to watching his 4-year-old daughter grow up.

“He went home in very good shape,” said Dr. Macchiarini. Macchiarini said that Mr. Lyles adult stem cells were placed onto the synthetic windpipe scaffold and grown in a bioreactor for two days, then transplanted into his body after removal of his tumorous trachea. The cells continue to grow and differentiate after implantation into the patient. Macchiarini pointed out:

“We’re using the human body as a bioreactor to promote regeneration.”

Because his own adult stem cells were used, there was no need for drugs to prevent his body from rejecting the transplanted windpipe; use of anti-rejection drugs, which have numerous side-effects, is a common problem in transplants using donated organs.

This is the second synthetic trachea transplant. The first transplant occurred in June 2011, and the results of that first synthetic trachea transplant were published in The Lancet. Macchiarini had done eight previous artificial trachea transplants, using cadaveric trachea stripped of cells and then coated with the patient’s own adult stem cells. The synthetic tracheal scaffold was designed and built by a Columbus, Ohio company and the bioreactor used to initiate growth of the adult stem cells on the scaffold for two days was built by a Massachusetts company.

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NIH Director Francis Collins has approved four more human embryonic stem cell lines as eligible for federal taxpayer funding. The latest approval brings the total to 146. The four new lines are all from UCLA. The new lines, designated by the deriving lab as “UCLA 7″, “UCLA 8″, “UCLA 9″, and “UCLA 10″, join six previous UCLA lines approved by NIH for taxpayer funding–UCLA 1-3 approved April 27, 2010 and UCLA 4-6 approved February 3, 2011. All of the lines were apparently derived from human embryos after the new NIH guidelines went into effect in July 2009. NIH doesn’t provide details on the cells themselves or their derivation.

In the meantime, Adult Stem Cells continue to provide the gold standard for patient treatment, and the only stem cell type with published positive results at improving health and saving lives.

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Scientists at the University of Pittsburgh School of Medicine have shown that adult stem cells from muscle of young mice can improve the health and extend the life of aged mice. The research team tested aged mice that are a model of an aging disease called progeria; the condition leads to advanced early aging. The idea was that in aged mice, the adult stem cells may have lost their vitality, with problems in proliferation (growth) as well as differentiation into other tissue types. However, when cultured in the same lab dish as muscle adult stem cells from young mice, the stem cells from aged mice recovered their ability to grow and differentiate. When young adult stem cells were injected into the abdomens of aging mice with progeria, the mice lived two to three times longer than expected and were healthier than aging control mice. Instead of losing muscle mass and moving slowly, the animals grew as large as normal mice. The Pitt researchers found evidence that the young adult stem cells secret a growth factor that delays the aging process.

Senior investigator Dr. Johnny Huard suggested that human muscle-derived stem cells could be stored at an early age and used when people age, allowing some rejuvenation of tissues and slowing the aging process.

The study was published online in Nature Communications.

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“The Wonder of Life” is a beautiful 1-minute video from Youth Defence in Ireland.

Happy Christmas!

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Just in time for Christmas, NIH Director Francis Collins has approved more human embryonic stem cell lines for taxpayer funding, bringing the total number of hESC lines at the federal trough to 142. Today’s approval is not all that surprising–the four new lines, from the University of Queensland, were recommended for approval by the Stem Cell Working Group at the December 9, 2011 meeting of the Director’s Advisory Committee. The Stem Cell Working group had also voted not to approve six lines from China.

The four new hESC linies that have been approved are not for clinical use, however. Subsequent to the meeting and before the latest approvals, NIH also approved two other hESC lines, from Mt. Sinai Hospital in Canada. Those two lines are also restricted:

NIH-funded research with this line may only be conducted at Mount Sinai Hospital and “other Canadian laboratories affiliated with the Canadian Stem Cell Network for further research or potential clinical use.”

In the meantime, the current and future patient benefits of adult stem cells continue to be ignored.

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In case you missed it, the appeal that was filed in the federal embryonic stem cell lawsuit regarding taxpayer funding, Sherley and Deisher et al. v. Sebelius et al., is moving forward.

The briefing schedule runs through March 12, 2012, and oral arguments are scheduled for April 23, 2012.

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NIH Director Francis Collins has approved another human embryonic stem cell line for federal taxpayer funding. The line, HUES PGD 14, was added to the NIH registry today, bringing the total number of approved hESC lines to 136. The line was created by Harvard University from a female embryo, and according to the information provided on the NIH website: “The embryo from which this hESC line was derived was determined through preimplantation genetic diagnosis to be affected with Spinal Muscular Atrophy.” This highlights the point made by Dr. James Sherley and Dr. Theresa Deisher in the ongoing Sherley et al. v. Sebelius et al. case, that there is a continued demand for more embryo destruction and more hESC lines, and the current NIH guidelines continue to provide an incentive for more human embryo destruction.

Meanwhile, adult stem cells remain the gold standard for patient treatments. You can see some examples at Stem Cell Research Facts.

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Awarded to Daniel Shechtman for his discovery of quasicrystals. Quasicrystals are regular patterns of packed molecules, but patterns that never repeat themselves. The structure of molecules that Shechtman discovered in quasicrystals was considered impossible at the time of his discovery, 1982. Shechtman had to fight a fierce battle against established science to get his information published and accepted in the scientific community.

Daniel Shechtman’s discovery of the quasicrystal pattern was wrong according to accepted textbook science. But Shechtman concluded that the scientific community must be mistaken in its assumptions. When he told scientists about his discovery, he was faced with complete opposition, and some colleagues even resorted to ridicule. But he persevered, and the scientific community was eventually forced to reconsider their conception of the nature of solid matter.

The Nobel committee publishes more information for the public as well as detailed scientific information. The information for the public concludes with this:

An important lesson for science
Daniel Shechtman’s story is by no means unique. Over and over again in the history of science, researchers have been forced to do battle with established “truths”, which in hindsight have proven to be no more than mere assumptions. One of the fiercest critics of Daniel Shechtman and his quasicrystals was Linus Pauling, himself a Nobel Laureate on two occasions. This clearly shows that even our greatest scientists are not immune to getting stuck in convention. Keeping an open mind and daring to question established knowledge may in fact be a scientist’s most important character traits.

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Awarded to Saul Perlmutter, Brian P. Schmidt and Adam G. Riess “for the discovery of the accelerating expansion of the Universe through observations of distant supernovae”. The two teams of astrophysicists studied several dozen exploding stars, called supernovae, mapping the most distant ones, and reaching the conclusion based on their studies that the Universe is expanding at an ever-accelerating rate. According to the Nobel committee, their findings “have helped to unveil a Universe that to a large extent is unknown to science.”

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Awarded to Bruce A. Beutler, Jules A. Hoffmann, and Ralph M. Steinman for their discoveries related to how the immune system is activated to defend against invaders.

Beutler and Hoffmann discovered receptor proteins that can recognize bacteria and other microorganisms and activate innate immunity, the first step in the body’s immune response. Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body, as well as the stage where the immune system develops a “memory” against subsequent infections. Taken together, their insights have shown some of the key activating principles for the stages of immune response, and also mechanisms for disease treatment and prevention.

UPDATE

The Nobel prize announcement was bittersweet for the family and friends of Ralph Steinman. Steinman died just days before the Nobel committee’s announcement that he had won. He succumbed to pancreatic cancer, which he had battled for several years, including using the knowledge gained from his Nobel award-winning research. Steinman was honored at a ceremony at Rockefeller University on Monday. Although the Nobel prize is not typically awarded posthumously, the Nobel committee has announced that Dr. Steinman’s selection will stand since the committee did not learn of his death until after it had reached its decision.

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Adult stem cells are being used extensively in the veterinary world to treat various animals, including horses and dogs. Now add goats to that list of creatures great and small that have benefited from the practical success of adult stem cells. Cinnamon the Goat has apparently become the first goat treated with its own adult stem cells. The procedure was performed by Kentucky veterinarian Dr. Clark Slone. The goat had some fat tissue removed and adult stem cells isolated from the tissue, then re-injected to treat damaged ligaments and joints. The vet expects that Cinnamon will be moving well within a month.

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Yesterday NIH Director Francis Collins approved three more human embryonic stem cell lines for taxpayer funding, bringing the total to 135. It’s been about a month since the last approvals, and just over three months since the rush to approve a large number of lines. Two of the three new lines from Cedars-Sinai Medical Center appear to have chromosomal abnormalities, as well as to be from destruction of full siblings.

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Scientists have reversed the aging process for human adult stem cells. Researchers at the Buck Institute for Research on Aging and the Georgia Institute of Technology have shown in laboratory studies that they can turn back the clock on the aging of adult stem cells, which are responsible for maintenance and repair of old and damaged tissues in the body. Adult stem cells are also the gold standard for patient treatments, now being used for dozens of diseases in thousands of patients around the globe.

The modern “stem cell hypothesis of aging” suggests that living organisms are as old as their adult stem cells, which explains the decline in regenerative power of our tissues as we age. Most cells show aging by the shortening of DNA sequences called telomeres, on the ends of chromosomes. As a cell ages, the telomeres get shorter, similar to a fuse burning down. But adult stem cells tend to maintain these fuses, so the researchers hypothesized that these repair stem cells must age by a different mechanism. They found that as we and our adult stem cells age, 65% of the DNA damage in self-renewing adult stem cells occurred within small sections of DNA called “transposable elements” or “retrotransposons”. Co-author King Jordan said:

“Retrotransposons were previously thought to be non-functional and were even labeled as ‘junk DNA’, but accumulating evidence indicates these elements play an important role in genome regulation.”

Young adult stem cells were able to suppress the activity of these genetic elements and deal with DNA damage, but older adult stem cells were less able to suppress them. Senior author Victoria Lunyak said:

“By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture.”

Next steps will include validating the rejuvenation of adult stem cells in lab animals. The study is published in the journal Cell Cycle.

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An Israeli company is conducting a clinical trial using a patient’s own adult stem cells to treat ALS (Lou Gehrig’s disease.) The method using adult stem cells was developed by professors at Tel Aviv University. Cells are taken from a patient’s own bone marrow and differentiated in the lab into astrocytes, cells responsible for nurturing neurons in the brain. By releasing neurotrophic factors, which are proteins that can protect brain cells, the former bone marrow adult stem cells can protect and preserve brain cell function.

Prof. Daniel Offen, one of the developers of the technique, says he and his team bypassed the ethical and safety issues inherent in embryonic stem cells by using adult stem cells derived from a patient’s own bone marrow. In addition, he notes that because the original cells are drawn from the patients themselves, the body should have no adverse reactions.

The clinical trial has been started at Jerusalem’s Hadassah Medical Center, but could be expanding soon to Massachusetts General Hospital in collaboration with the University of Massachusetts Medical School.

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Stanford University is reporting that they have injected the fourth patient with embryonic stem cell-derived cells in Geron’s experiment on patients with a specific type of spinal cord injury.

Geron had previously announced the first and second patients, but not the third patient who was apparently injected in the last couple of months in Atlanta. Up to ten patients may be tested in the initial experiments. Patients will be monitored for 15 years because of the significant risk of tumor development. Scientists are still trying to overcome the cancerous potential of embryonic stem cells.

Adult stem cells have already successfully improved dozens of spinal cord injury patients, documented by peer-reviewed publications, and all without concerns for tumors, transplant rejection, or harm or destruction of the stem cell donor.

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Attorneys for Dr. James Sherley and Dr. Theresa Deisher have filed a Notice of Appeal in the Sherley et al. v. Sebelius et al. case. The appeal asks for the court to reverse the District Court’s ruling and stop federal taxpayer funding of human embryonic stem cell research, which relies on the destruction of human embryos. The U.S. District Court had reluctantly ruled against Dr. Sherley and Dr. Deisher in July. The next steps will be for the U.S. Court of Appeals to schedule submission of legal briefs and oral arguments in the case.

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Peyton Manning, quarterback for the Indianapolis Colts and four-time NFL MVP, apparently went to Europe to get an adult stem cell procedure on his neck, according to a report Sunday by Jay Glazer of Fox Sports. Manning has had three surgeries on his neck in the last 19 months, Little detail was available, but the information indicates that the procedure may have used adipose (fat) derived adult stem cells from Manning’s own body; this autologous procedure (using your own adult stem cells) bypasses any problems of transplant rejection and is relatively safe. Manning’s adult stem cells may have then been injected around the site of his problem vertebra in the neck, to assist healing and help with spinal disc fusion. In that respect, it sounds similar to the procedure that Texas Gov. Rick Perry received in Houston, Texas, for his back problem.

Glazer indicates in his report that Manning went to Europe for the adult stem cell procedure because it is not yet approved in the U.S. This may be true, since Europe is well ahead of the U.S. in current use of stem cells for actual patient treatments. ALL of those treatments involve adult stem cells, of course.

Glazer’s suggestion that only embryonic stem cell treatments are available in the U.S. is inaccurate, however. It’s true that the only three approved clinical trials experimenting with embryonic stem cells are in the U.S.; with a total of four patients known to have been injected with the dangerous embryonic stem cells, and no results as yet.

But there are actually over 2,200 FDA-approved adult stem cell clinical trials ongoing or completed, most of which in this list are in the U.S. That includes several adult stem cell trials using adult stem cells for spinal fusion, and even a couple of adipose-derived adult stem cell trials in Indianapolis. Maybe Peyton realized that only adult stem cells had real potential for safe and ethical treatment of patients. Hopefully, he will talk about his experience so more people understand the difference between embryonic and adult stem cells.

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