OOPS! Turns out those tired old useless hESC lines were… extremely valuable! They were, and are, the gold standard for human embryonic stem cells. They’re what almost every hESC scientist has studied. They’re thoroughly characterized and familiar cells.

Now, a number of scientists are realizing just how valuable are those well-characterized hESC lines. Despite the increased funding and many more lines from which to choose, many hESC scientists want… those tired old “Bush” lines. They are complaining that so far the new policy is more of a burden than a boon to their work. Some of the scientists say they’re stunned by the irony. Apparently ideology and desire trumped science.

According to Charles Murray at the University of Washington-Seattle

“The situation at the moment is worse than it was under the Bush administration. Because of this, we are going to waste a lot of time.”

Timothy Kamp at the University of Wisconsin says of the old hESC lines

“They are the main workhorses for many of our projects.”

Julie Baker of Stanford says

“It’s a huge setback because we’ve spent about six years studying the biology of that particular line. So they’ve just wasted millions of dollars and lots of resources, which just seems outrageous to me.”

This really shouldn’t come as a surprise. There were already rumblings early in the process about whether the old lines would be funded, with one researcher saying that the new Obama hESC policy had a “tremendously detrimental effect on our research.”

But there were also earlier warnings as well about the science. In April 2006, an article noted almost in passing that 85% of the world used the “Bush” approved lines, whether or not they got NIH funding. The preference was clearly for the best-characterized and most useful lines. Another paper published in October 2006 also found that most hESC researchers around the world used those lines, with a clear preference for three (H9, H1, H7) of the oldest lines originally derived by Thomson in 1998. (Note that (originally 78 lines were identified as “approved”, an effort to ensure that all possible cells were eligible for funding.) In August 2009 another paper repeated the point, showing the predominance of hESC research used just two of the original lines (H1, H9).

Recently, the first (H1) of the tired old lines was approved. But many scientists are still waiting for their favorite, most scientifically useful, line to be approved for federal taxpayer funded research. It remains to be seen whether NIH will propose another change in its so-called ethical guidelines, this time to focus on science rather than ideology. So far the focus has not been on the patients first and the adult stem cell research already helping thousands. Ideology may trump science again.

“From a scientific point of view, it’s making us re-evaluate the view of the stem cells that come from adults. It challenges the dogma that there is one type of stem cell.”

The study has significance for stem cell patient treatments as well. According to Goodell:

“People have been looking for purer and purer stem cell types. In doing that, they may not be getting all the stem cell types they need. Maybe in the clinic, it is better to have less pure types.”

“This study will have a major impact on the treatment of any blood-related disorder that requires a stem cell transplant.”

Previous work from Dr. Rafii’s lab had demonstrated that endothelial cells are not “passive conduits”
for delivery of oxygen and nutrients but also produce novel stem-cell-active growth factors.

The breakthrough promises broad clinical benefits, from bone marrow transplantation to therapies for heart, brain, skin and lungs. If the system continues to be validated, physicians could use any source of hematopoietic (blood-forming) stem cells, grow large numbers, and bank the adult stem cells for transplantation into patients.

The paper is published in the journal Cell Stem Cell.

A Brazil-Florida collaboration found that adult stem cells injected directly into the heart could relieve angina. The researchers used injection directly into the heart based on previous results showing higher uptake of cells administered in this way. All eight of the angina patients in the study benefitted. Lead author Dr. Nelson Americo Hossne, Jr. said:

“For our patients, angina symptom relief began as early as three months post-procedure with continuing improvement through the twelfth month and sustained improvement past 18 months. Symptom relief improved in all patients, suggesting that the effect is sustained, not transitory.”

The authors conclude that their results show the procedure to be safe and effective, and suggest neoangiogenesis, the stimulation of new blood vessel growth, as the main stem cell mechanism of action in these patients.

A separate published study by Chinese scientists suggests that a small protein called apelin, which affects the strength of muscle contraction, may play a role in adult stem cell repair of heart. Twenty patients experiencing severe heart failure were treated with their own bone marrow adult stem cells, while another twenty heart failure patients were treated with standard medications; both groups were compared against twenty healthy adults. All twenty of the heart failure patients treated with adult stem cells showed significant improvement in cardiac function within 21 days of treatment, while the standard medication patients showed no improvement. Interestingly, the adult stem cell-treated patients showed a large increase in levels of apelin, correlated with the improvement in cardiac function. They postulate that the secretion of apelin is induced by the grafted adult stem cells.

Both studies were published in the journal Cell Transplantation. Dr. Amit Patel of the University of Utah School of Medicine and an Editor of the journal said:

“Both studies demonstrate a possible mechanistic approach in a clinical trial either. These important findings further enhance the understanding of the use of bone marrow derived cell therapy for the treatment of cardiovascular disease.”

The study follows a previous report of successful adult stem cell treatment for leukemia that also appears to have controlled HIV infection in the patient. The doctors specifically used an adult stem cell donor whose cells lacked the CCR5 molecule.

A couple of examples of recently published studies.

In a paper published February 15, 2010, Oregon scientists showed that they could use bone marrow-derived adult stem cells to treat a rat model of retinitis pigmentosa. Visual function was significantly preserved in this study. An added benefit was that the cells could be easily grown in culture and administered intravenously; once injected, they traveled to the retina where they exerted their protective effect. The study highlights the possibility of using a patient’s own adult stem cells for treatment of retinitis, diabetic retinopathy, and macular degeneration.

A study by Canadian and Japanese researchers used human retinal stem cells that had been modified to increase their differentiation potential. When injected into the eyes of mice, the adult stem cells survived and differentiated into photoreceptors. Injected into a mutant mouse strain that lacks functional photoreceptors, the adult stem cells significantly improved visual function. The study was published online in the journal Stem Cells December 11, 2009.

In Louisville, they are close to initiating a clinical trial using adult stem cells for treatment of macular degeneration.

Looking at a different part of the eye, adult stem cells have already been used successfully in patients to treat corneal blindness.

There are other examples of real adult stem cell successes for visual repair if we want to go back further. And unlike “potential” embryonic stem cell experiments which rely on sacrificing some human beings, adult stem cell research doesn’t require destroying the cell donor, instead often using the patient’s own adult stem cells for the treatment. Real success and real science.

Wait a minute. Complication issues?

However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin.

I would hope that they’d eliminate the complications first, not just decrease the incidence. And just how many of the mice are represented by “some”?

The abstract in the journal Transplantation gives a bit more detail:

Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes.

So, a quarter of the mice showed improvement, but more than half showed complications including tumors…

So much for an embryonic success.

Then Jennifer signed up for an adult stem cell study run by Dr. Richard Burt, chief of the Division of Immunotherapy at Northwestern University Feinberg School of Medicine. Her adult stem cells were collected and she received chemotherapy to knock out the rogue immune cells attacking her nervous system. Shortly after, on April 1, 2005, Jennifer received a transplant of her own adult stem cells and her immune system, now rebooted, began to rebuild itself. The process was slow and grueling, but she has taken no medication for the disease since 2008. Today, almost five years since her transplant, she is nearly symptom-free.

“This is my life, a healthy life. Back to normal.”

Rick points out:

“It’s really important to us that people know (about the stem cell procedure), because we found out about this from watching TV. If we hadn’t seen that broadcast, she probably wouldn’t be here today.”

The Osmans have a website to tell Jennifer’s story and communicate with other CIDP patients. Jennifer is looking forward to updating the site on April 1, five years to the day that she received her adult stem cell transplant.

You can see a video of Amy Daniels (another of Burt’s patients) and her story of treatment for scleroderma, as well as other patient stories, at Stem Cell Research Facts.

Dr. Burt has performed the first adult stem cell transplants in the country, and sometimes in the world, for patients with many autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, Crohn’s disease, systemic lupus erythematosus, Type I (juvenile) diabetes, and of course CIDP. Burt said Northwestern has done about 350 of these transplants so far. A number of his clinical trials are currently ongoing, including one for CIDP. Dr. Burt says:

“When I first came up with this idea … people said, ‘Why are you wasting your time?’ I ended up following my passion, and it’s been fabulous. The amazing thing is, traditional medicine has just kind of come to a stop with these patients. What we’ve done is we’ve changed that.”

According to Burt, the treatment has come a long way, as Medicare and several insurance companies will now cover it.

Helen Thomas, 80, of Hastings, Michigan is one of those people. Helen’s painful circulatory problem in her leg meant she had trouble walking, rarely left home, and was facing amputation of her leg. But her physician, Kenneth Merriman of Hastings, asked around at a medical conference and found Dr. Randall Franz, who was doing a clinical trial at Grant Medical Center in Columbus, Ohio. Franz injected Helen’s own adult stem cells into her leg, causing new blood vessels to grow. Helen is now up and about, back to normal.

“It was a miracle. I’m walking, and I wouldn’t be walking without the stem cells. I have my leg. They saved my life. I told them they saved my life.”

Helen’s daughter Mary said:

“It’s just life-changing”

Initial patient results have been published in the Journal of Vascular Surgery.

HT: Andy McDonald