US Military & Regenerative Medicine

2DBEE37E-50C6-4DE5-B306-66FCAE86485D.jpgMcGowan Institute for Regenerative Medicine affiliate member David Baer, PhD, Director of Surgical Research, U.S. Army Medical Research and Materiel Command’s Institute of Surgical Research (ISR), Ft. Sam Houston, TX, and his colleagues there in the last few years have looked into about two dozen hemostatic dressings for use on the battlefield. The Pentagon medical officials announced recently that two new first-aid products are being sent into the combat theater and they could save more service members’ lives.

Test results from the ISR showed Combat Gauze field bandages and WoundStat granules both demonstrated marked improvements over what’s currently used in the field, Army Col. (Dr.) Paul Cordts of the Army surgeon general’s office said.

Excessive blood loss is the No. 1 killer on the battleground, Dr. Cordts, a surgeon, said. Both products can stop bleeding quickly in wounds where tourniquets can’t be used, he said. Combat Gauze uses kaolin, a fine, white clay, to stop bleeding, he said, and WoundStat granules react with blood to form a barrier, preventing more bleeding.

More than 92 percent of troops wounded in Iraq and Afghanistan survive their injuries in combat, the highest percentage of any war, according to U.S. Army Medical Department officials. Army Master Sgt. Horace Tyson, a combat medic, said he attributes the high number of people being saved to the advanced tools medics have, such as dressings that stop or slow blood flow from wounds.

Although the new hemostatic dressings are promising great improvements, Dr. Baer said it doesn’t mean officials aren’t still looking for the next line of products that could offer even more improvements. ISR scientists will continue their efforts for even more cutting-edge products to save lives, he said.

The new dressings are expected not only to save more lives, but also to bring significant cost savings to the government, Dr. Cordts said. Combat Gauze is less than $30 per dressing, compared to the currently used HemCon bandage, which uses chitosan from shrimp shells to stop blood and costs $88 per bandage. WoundStat also is less expensive than the QuikClot granules it replaces.

After many years of more or less ignoring the topic, big pharmaceutical companies (revenue in excess of $3 billion) finally are paying attention to stem cells as vehicles of drug testing and future regenerative medicine therapies. The pioneering and highly risky stem cell field has been so far mostly the domain of academic laboratories and small biotech companies.

Pfizer’s growing and various interests in stem cells

Research

Pfizer Inc. is one of the biggest research-based pharmaceutical company and ranks number one in the world in sales. The company opened a “regenerative medicine unit” in Cambridge, Mass. last year and now moves to the other Cambridge, U.K. to open another similar shop around November. On the other hand Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company. The growing interest can be partly explained by the role that induced pluripotent stem cells can play in drug testing and the first uses will probably be in early-stage safety testing. The risk-taking in the new and unknown field is especially interesting considering the tough times in the pharma industry.

These cells will be tremendous in drug discovery,” an R&D exec told Reuters. “They will help us understand personalized medicine, genetic variation, ethnic populations, what biomarkers to follow.” John McNeish will run Pfizer’s U.S. unit, which will focus on heart disease and diabetes. In November, the company plans to open a standalone regenerative medicine unit in Cambridge, United Kingdom, to focus on research in ophthalmology and diseases of the central nervous system. McNeish said the overall operation will eventually have 50 to 60 scientists working on stem cell therapies, and they are working with academic researchers and smaller biotech companies.

Abstract:

Pfizer Inc. is one of the biggest research-based pharmaceutical company and ranks number one in the world in sales. The company opened a “regenerative medicine unit” in Cambridge, Mass. last year and now moves to the other Cambridge, U.K. to open another similar shop around November. On the other hand Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company. The growing interest can be partly explained by the role that induced pluripotent stem cells can play in drug testing and the first uses will probably be in early-stage safety testing. The risk-taking in the new and unknown field is especially interesting considering the tough times in the pharma industry.

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GlaxoSmithKline collaborates with the Harvard Stem Cell Institute

Research

GlaxoSmithKline, the world’s second-biggest pharmaceutical company and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement.

GSK’s investment, one of the largest by a pharmaceutical company in stem cell science, will support innovative research at Harvard University and in at least four Harvard-affiliated hospitals in the areas of neuroscience, heart disease, cancer, diabetes, musculoskeletal diseases and obesity. In addition, GSK will fund an annual grant, which supports early stage research in stem cell biology, as part of HSCI’s seed grant program “GSK believes stem cell science has great potential to aid the discovery of new medicines by improving the screening, identification and development of new compounds. We have carefully chosen the Boston biomedical community to collaborate with on this important venture. It has the highest concentration of leading stem cell scientists, and the Harvard Stem Cell Institute is the epicentre of that community,” said Patrick Vallance, Head of Drug Discovery at GSK.

Abstract:

GlaxoSmithKline, the world’s second-biggest pharmaceutical company and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement.

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Big pharma has begun cooperating with both academia and startups by investing several millions of dollars in regenerative medicine. Some signs of the upcoming trend: GlaxoSmithKline and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement while Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company.

Stem Cells for Safer Medicines, or SC4SM, [a collaboration to develop stem cells for safety testing of new drugs through a public-private partnership and an independent not-for-profit company], is backed by 3 European big pharmas, GlaxoSmithKline, AstraZeneca and Roche. More involvement, could mean in-house research labs. Pfizer now has its “regenerative medicine unit” in Cambridge, Mass. with the plans to open another similar shop in Cambridge, England, by late 2008.

Regenerative Medicine

Methods on the cusp of profoundly impacting their field, areas in which methodological developments are needed and updates on some of last year’s picks for Methods to Watch: here is our (subjective) selection for this year.

induced pluripotency

Methods to reprogram somatic cells to pluripotency have improved and will improve further; more biological studies of these cells are forthcoming.

When, a year ago, we picked induced pluripotent (iPS) stem cells as an area worth watching, it had only recently been demonstrated that the basic approach—expressing a defined set of factors in somatic cells to render them pluripotent—worked in humans.

The potential of this system, for understanding early development, as a research model for disease, or even in future applications in the clinic, was apparent, but several questions remained. There has since been progress in many directions, in work from several labs. By starting with different cell types, or by using small molecules, the efficiency of reprogramming has been improved up to 100-fold and has allowed iPS cells to be generated without one or more of the reprogramming factors. Screens for small molecules that can improve the results even further will doubtless continue.

The range of cell types that have been rendered pluripotent has also increased and now includes pancreatic beta cells, neural stem cells and human keratinocytes, among others. Human iPS cells have in addition been generated by reprogramming somatic cells from individuals affected with genetic disease. And recently, transient expression of the reprogramming factors has been used to generate mouse iPS cells, circumventing problems that can result from viral integration into the genome.

In addition to further technical improvement, continued studies of iPS stem cell biology, whether at the level of gene expression, epigenetics or differentiation, will be critical for harnessing their full potential. This is still an area worth watching, we bet. Natalie de Souza

Synthetic life

After constructing a synthetic genome, the challenge is to prove its functionality. A major long-term goal of synthetic biology is to design a living organism with a minimal, redundancy-free genome, custom made for certain functions. The short term challenge lies in assembling a whole genome, nonessential genes and all, from raw chemicals.

In 2008, technical breakthroughs were achieved for genome assembly. J. Craig Venter and colleagues used an in vitro recombination strategy to recombine oligonucleotide cassettes of 24 kb into larger modules and then moved to yeast for the final recombination steps to obtain the 582.9 kb genome of Mycoplasma genitalium (Science 319, 1215–1220; 2008).

Similarly, the group led by Mitsuhiro Itaya assembled the 134.5 kb genome of rice chloroplasts with an in vivo recombination strategy in which domino clones of 4–6 kb are assembled in Bacillus subtilis (Nat. Methods 5, 41–43; 2008). Testing these synthetic genomes for functionality will be the next step on the path to synthetic life.

The Venter group had shown previously that they can swap the entire natural genome of M. mycoides for that of M. capricolum, and they are now looking to transplant the synthetic M. genitalium genome into M. capriolum— an endeavor not without technical challenges. It remains to be seen whether the synthetic genome assembled in yeast, and consequently not protected against bacterial restriction nucleases, will replicate and indeed encode a living bacterium.

Another aspect that will need optimizing is codon usage. The genomic fragments should be nontoxic for the host within which they assemble. The completed genome, however, has to be transplanted into a final recipient that will translate the genetic code into functional proteins.

Understandably, this prospect of custom-building life raises concerns and, like any technology, it can evoke horror scenarios, but it also holds tremendous promise for both understanding biology and harnessing its power for technology and medicine. Nicole Rusk

McGowan Institute for Regenerative Medicine

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from Pitt Research Efforts

McGowan Institute for Regenerative Medicine congratulates its faculty members—Marco Zenati, MD (pictured top), Patrick Kochanek, MD (middle), and Dennis McNamara, MD (bottom)—for their 2008 research technology transfer efforts. As reported by the University Times, three start-up companies based on innovations developed at Pitt were created in fiscal year 2008, bringing the total number of start-ups to 69 since Pitt’s Office of Technology Management (OTM) opened in 1996.

The start-ups created in 2008 all were based in the health sciences. They are:

· Cardiorobotics, Inc., which is developing robotic probes for use in minimally invasive cardiac and other surgeries. Marco Zenati, professor of surgery, is a company co-founder and chairs its scientific advisory board.

· EPR-Technologies, Inc., which uses new emergency hypothermia procedures to put trauma victims into temporary suspended animation until treatment can be obtained. The process and equipment were developed by Patrick Kochanek, Xianren Wu and William Stezoski, all of the Department of Critical Care Medicine, and Samuel Tisherman of the Department of Surgery.

· Prevencio, LLC, which was formed to utilize discoveries by William LaFramboise of the Department of Pathology and Oscar Marroquin, Dennis McNamara, and Suresh Mulukutla of the Department of Medicine. The researchers developed a series of protein signatures detectable in body fluids that can reveal signs of vascular disease.

Marc Malandro, associate vice chancellor for Technology Management and Commercialization, stated that OTM is “excited to see a growing number of innovators participating in this process, suggesting that technology commercialization continues to play a growing role as part of the University’s overall goal to see products developed from its research benefit society.”

By Steven S. Clark, December 2008 – As Wisconsin observed the 10-year anniversary of James Thomson’s embryonic stem (ES) cell discovery, some wonder whether the ensuing controversy over the destruction of human embryos has been worthwhile. In those 10 years, no therapies have come from the discovery, so were opponents correct that this research was not only unethical, but also irrelevant?

While there have been no headline-grabbing ES-based therapies, the technology is surely changing the way that medicine is practiced. This was illustrated by recent events in Madison, including the World Stem Cell Summit in September and a more recent celebration of the ten-year anniversary of Thomson’s discovery put on by the Wisconsin Academy of Arts and Sciences.

The anniversary event featured keynote talks by Thomson, the University of Wisconsin-Madison professor cellular biologist, and Michael West, CEO of BioTime, Inc. and founder of Geron, a West Coast stem cell company.

Thomson sounded his usual cautionary note, saying it will be very difficult to use ES cells to directly treat disease. But he also said that even if they never make it into the clinic, ES cells would profoundly affect the future of medicine because they provide laboratory access to human tissues that had been inaccessible before. This allows scientists to see what goes wrong with the specific cell types that cause Parkinson’s and cardiovascular diseases, diabetes, and other maladies. This, Thomson said, will lead to the development of new drugs and therapies to treat and prevent such diseases.

Thomson also explained that the different cell types that can be derived from ES cells enable researchers to directly test new drugs on different human tissues. He suggested that this will both dramatically reduce the number of animals used in drug and toxicity testing and allow more precise assessment of new drug efficacy and toxicity.

This was put into perspective at the Stem Cell Summit by John McNeish, head of Pfizer’s regenerative medicine efforts. He said that 10 to 16 percent of all new drugs fail during Phase I clinical trials alone due to cardiotoxicity. Many more drugs fail due to liver, kidney, and other organ-specific toxicities.

Overall, about 92 percent of new drugs that enter clinical trials fail due to lack of efficacy or to toxicity, according to the Food and Drug Administration. This means that potential drug toxicity is inefficiently measured in current animal models, making drug makers gamble early on that their new drugs won’t show organ-specific toxicity – a gamble they lose nine times out of 10.

ES cell technology therefore promises to provide tissues on which to test and eliminate potentially toxic drugs much earlier in the development pipeline, potentially saving billions in drug development costs, according to the FDA.

ES cell-derived research tools enter the marketplace

Thomson and others from UW-Madison founded Cellular Dynamics International to grow different tissues from ES cells. According to Tim Kamp, a UW-Madison cardiologist and CDI co-founder, the company now sells heart cells to Roche and Covance for drug testing purposes. CDI grows the heart cells in-house and then sells them as research tools. Thus, they retain control of the ES cells and the developmental process, while providing a renewable stream of cellular tools that researchers can purchase.

At this time, CDI only markets heart cells, Kamp said. But, according to Chris Kendrick-Parker, CDI’s chief commercial officer, the company either has agreements with or is talking to the “all of the top 20 pharma companies” to provide cells for toxicity testing.

Besides CDI, Geron, and San Francisco’s VistaGen Therapeutics also use ES cells to produce cells from the heart, pancreas, liver, and other organs for similar purposes. The European company Cellartis provides AstraZeneca with ESC-derived liver cells for toxicity testing, but only at very low numbers that are not useful for high-throughput-screening of new drugs. Cellartis also provides Pfizer with embryonic cells to test for birth defects.

Clearly, ES cells as drug testing and research tools is a growing international market. At the Stem Cell Summit, Pfizer stem cell expert John Hambor said this market currently stands at $1.5 billion and is predicted to grow 20 percent annually in the foreseeable future.

Clinical trials on the horizon?

Michael West is more optimistic than Thomson that ES cell-based therapies soon will happen. He cited the very high interest in the technology shown by several biotech and pharmaceutical companies as the driving force that soon will propel ES cells into the clinic.

Some biotechs already are pushing hard to begin clinical trials of ES cell-based therapies. For instance, last spring Geron submitted an Investigational New Drug (IND) application to the FDA for permission to undertake the first ES cell clinical trial to treat spinal cord injuries. According to the company, the trial had been in the works for four years, but the FDA issued a clinical hold because they have not yet established safety and efficacy guidelines for ES cell-based therapies. According to an article last May in the science journal Nature, there also is speculation that President Bush’s objection to ES cell research helped force the FDA to put the trial on hold.

Geron also is planning ES cell clinical trials for heart disease, while Advanced Cell Technology in Los Angeles is poised to submit an IND to use these cells to treat macular degeneration. San Diego’s Novocell, with funding from Johnson & Johnson, is preparing for ES cell clinical trials to treat diabetes.

After 10 years…

So, 10 years after Thomson’s discovery, ES cells are just now entering the market as research tools for drug and toxicity testing and clinical trials loom on the horizon. At this point, the holdup is so the FDA can figure out how to monitor the trials.

Furthermore, with the Obama administration, political constraints on the FDA to approve ES cell-based trials will likely be removed next year.

Regenerative Medicine Conference

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The 8th Annual McGowan Institute for Regenerative Medicine Scientific Retreat is set to take place on March 9-11, 2009 at Nemacolin Woodlands Resort. An informal mixer will occur on the evening of March 8, 2009. Under the leadership of Dr. William Wagner, the program committee is planning an exciting group of speakers and topics. The program will include distinguished guest speakers, a poster session, and potential external partners and collaborators, so there will be multiple opportunities for networking and collaboration. The registration deadline is February 15, 2009 (or sooner; no reservations will be accepted once the reservation quota is filled.)

Regenerative Medicine

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A story of three strong women who took control of their own destiny – Nelly van Iwaarden (75) and her two daughters Francien (55) and Anneke.

XCell-Center, Cologne, Summer/Fall 2008 — Anneke was born 43 years ago with severe cerebral haemorrhages. Her diagnosis: cerebral palsy (CP). CP sufferers are subject to apoplexies which lead to paralysis of the arms and legs, seizures and the loss of control of almost all muscles.

At five years of age, Anneke was put in a home for the disabled by the Dutch authorities. Thirty years later she fled from there, travelling twenty kilometres in a wheelchair back to her family. Her clenched muscles had given her back a double-S shape, her left arm was fixed at a strange angle behind her head and her body was twisted to the right and forwards. Her elbow joints and inguinal abdominal region were raw and openly bleeding. Anneke had uncontrolled saliva discharge. She couldn’t sit up by herself in a chair or turn in bed. She wet the bed every night. All accompanied by an incredible pain in her oppressed body.

Her sister Francien and mother Nelly built a fantastic handicapped accessible home with the inheritance from Anneke’s father, who had died in 1999, and searched desperately for ways to help Anneke. The doctors had already given up on the young woman a long time ago. Francien came across an article in a magazine about stem cell treatment in the XCell-Center.

Our specialists didn’t want to get the family’s hopes up too high in the beginning. However, following an in-depth examination, a joint decision was made to inject Anneke’s own adult stem cells into her spinal canal.

Francien: “24 hours later, there wasn’t any saliva running out of Anneke’s mouth anymore”. Then everything happened in rapid succession: her left arm loosened; she could sit up straight again; her arm joint opened up; she could move her legs. Every day an improvement.

Today, following her third stem cell treatment, Anneke can laugh again and take part in family life. She can sit up straight by herself in her wheelchair, read again (after 17 years of not reading), write and knit. She can turn around in the bed herself and go to the toilet with help from her sister. Following the stem cell therapy, she can even maintain an upright posture again and has been able to stand for the first time in her life. Several times a day, she exercises her leg muscles while standing on an electric vibrating plate and she trains her arms and fingers using dumbbells.

Francien: “Our motto is practice, practice and more practice.” And Nelly, Anneke’s mother, adds with a smile: “We haven’t let things get us down. The exercises have only been made possible by the stem cell treatment and all three of us have seen an incredible enhancement in our quality of life.”

Regenerative medicine at stanford
A Conversation With Renee A. Reijo Pera

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Alex di Suvero for The New York Times
‘In my lab, we’re using stem cell research to look for ways to make fertility treatments safer and more rational.’ – Renee A. Reijo Pera

As director of Stanford’s Center for Human Embryonic Stem Cell Research and Education, Renee A. Reijo Pera, 49, a professor of obstetrics and gynecology, works at ground zero of the controversy over human embryonic stem cells. She uses human embryos to create new cells that will eventually be coaxed into becoming eggs and sperm. In other research, she has also identified one of the first genes associated with human infertility. The questions and answers below are edited from a two-hour conversation and a subsequent telephone interview.

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Alex di Suvero for The New York Times

GROWTH OPERATION An incubator with petri dishes

for stem cell research.

By CLAUDIA DREIFUS

Published: December 15, 2008

Q. WHY ARE YOU TRYING TO CREATE HUMAN EGGS AND SPERM?

A. Because in doing so, we may find the answer to disorders like Down syndrome and some neurodegenerative diseases that develop in the egg, sperm or embryo. It’s our hypothesis that if you don’t treat your DNA right in the first day or two of life, you could end up with diseases and conditions. So by learning what nature does and repeating it in a Petri dish, we hope to find out what has gone wrong — and then, eventually, how to correct it.

Q. HOW FAR HAVE YOU GOTTEN IN THIS QUEST?

A. We’re about halfway there, though I’m not sure if we’ve completed the easy or hard half. In a dish, we’ve gotten stem cells to make meiotic germ cells, the cells that give rise to eggs and sperm. What we haven’t been able to do yet is to figure out which supplements should be fed to the cells to get them to become germ cells capable of making embryos. Optimistically, we are three to five years from being able to do that.

Q. IN SPEECHES, YOU SAY THAT STEM CELL RESEARCH SHOULD BE THOUGHT OF AS A WOMEN’S HEALTH ISSUE. WHY?

A. Because in my lab, we’re using stem cell research to look for ways to make fertility treatments safer and more rational.

Considering all the heartbreak and expense of infertility treatments, this sort of research is something I believe women have a big stake in defending.

Right now, we don’t fully know what a healthy embryo in a Petri dish looks like. Because of this, I.V.F. clinics often insert multiple embryos into women to try to increase the odds of a successful implantation. Patients frequently have multiple births or devastating miscarriages. Half the time, the embryos don’t make it. If we could figure out what a healthy embryo looked like and what the best media was to grow it in, we’d cut down on that.

Q. WHEN GEORGE BUSH ISSUED HIS AUGUST 2001 PROHIBITION AGAINST FEDERAL FINANCING OF NEW STEM CELL RESEARCH, WHAT DID YOU THINK?

A. First, I was stunned that a president was talking about biological science at all! After I caught my breath on that, I was grateful he didn’t order an outright ban on all research in this area.

As you may recall, his order banned federal funding for new stem cell lines, but permitted work on older colonies of stem cells, derived by embryos — “lines” — already in existence. Of those he permitted, there were supposed to be something like 60 or 70 lines, though reports are there are actually only about 20 lines one can work on. I believe there are really only 11 that grow well.

There’s been bad news and good news. Surprisingly, because scientists were limited to working with these very few lines, we’ve learned a lot about this one small group of embryonic stem cells. We’ve learned a lot about the genetics of these lines, and we are able to make comparisons between them. This might not have happened if researchers had been using all kinds of different lines from all over the place. The bad news was that the available lines turned out to be, generally, of poor quality — many were grown in a medium that contained animal products. For studying human reproduction at the level we are, you wouldn’t want to use them. The bottom line is: Although we have improved our methods to make embryonic stem cells, we’re still limited to using these poor-quality stem cell lines, which are not valuable for learning about human embryonic development.

We hope in the future we’ll be able to study newer lines made under less restrictive conditions. I hope there will be a change in policy.

Q. WELL, THEN, WHAT DO YOU USE IN YOUR LABORATORY NOW?

A. Our lab isn’t federally funded. We get our money from the $3 billion California stem cell initiative. We make our own stem cells from embryos donated by I.V.F. families.

Q. DO YOU HAVE MORAL QUALMS ABOUT USING HUMAN EMBRYOS IN YOUR RESEARCH?

A. I can’t say I do. And I’ve really searched myself about this. I grew up a deeply religious Christian — I’d go off into the woods and sing hymns. My sister is an Evangelical. I’m sure there have been moments in my life when I haven’t been a model Christian, but my work on embryonic stem cells isn’t one of them.

Think about it: we study embryos donated by couples who finished their I.V.F. treatments. They would be destroyed anyway. Nationally, the clinics discard about 400,000 unused embryos every year — and yet few people consider I.V.F. clinics “immoral.” Stem cell researchers use about 10,000 of those about-to-be-discarded embryos. And in learning from them, we are getting information that we can get nowhere else, that will make mothers and babies healthier.

There are people who believe that we when use embryos for research at all, our society becomes hardened. I’ve searched myself on that and I don’t think I’m hardened. I can honestly say I still get goose bumps when I see embryos develop. You hope you are humble enough to take in the information and not change your course.

If there was truly a substitute that was better for understanding human development than embryo research, that is what I’d do. But there isn’t. That’s where the data is. I think that it is not good to throw human embryos away — without studying them.

“My condition after 1 year of stem cell treatment” – Story of Mr. Wolf, a patient with Parkinson’s disease

Summer/Fall 2007 to 2008

The facts about my therapy experiences.

1st treatment

On July 26, 2007, I received an implantation of 10 million stem cell units at the

XCell-Center in Cologne, Germany

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After this treatment, I slowly phased out the following medication over a period of 4 weeks:

Amantadine 200/100 3 x daily

Levocomp 100/50 3 x daily

Cabaseril 1 mg 2 x daily

Levodopa/Carbidopa 200/50 Retard 2 x daily

Acilect 1 mg 1 x daily

Comtesse 200 3 x daily

Total:
14 tablets daily

Cost:
771.77 € / month
12 months = 9,261.24 €

Afterwards, I had no pain and had stopped taking any medication.

The symptoms typical of Parkinson’s disease, which had been causing my condition to decline unstoppably with all the attendant consequences, had vanished.

· No slight tremor.

· No back pain.

· The feeling of having painful, leaden legs disappeared.

· No dyskinesia (powerful twitching) in my legs at night.

· The feeling of dizziness when getting up and climbing stairs disappeared.

The urge to go to the toilet 3-4 x a night decreased to just once a night or not at all.
It again became a pleasure to do one hour of sport every day: cross-country running (jogging) and walking (hiking), cycling, skiing, playing tennis, and most recently motorcycling.

Recently I have found that I am rolling my feet more and more to cushion the impact when running.
Because I no longer have side-effects from the medication, I can now easily drive a car without feeling tired.
The same applies to my newly acquired motorbike.

I also no longer suffer from dizziness after car/motorbike trips, which means I can now undertake longer journeys, also with other means of transport.

Cleaning my teeth and buttoning my shirt is becoming easier all the time.

I can also say that fresh water – and not only this – again tastes fresh.

As a follow-up

i.e. after the 1st treatment on July 26, 2007, I went for tests at the Neurological Clinic in Saarbrücken on January 28th, 2008. Please consult the report on my website

http://www.wolf-sb.de/PersoenlicherBrief.html

The test report does not indicate that the stem cell therapy had negative results.

Moreover, a psychological test revealed,

Quote:…Compared to Parkinson patients, Mr. WOLF actually gave a performance which could not be bettered.

2nd treatment

Another 10 million stem cells on February 22, 2008

After the 2nd treatment on February 22, 2008, I went to Munich on March 28, 2008 for more tests; see the report on my website.

The neurological tests showed,

quote:…The stem cell therapy had gratifying, very positive results, as it was followed by the relief of all symptoms.

I can now only confirm that Mr. Wolf’s condition is exceptionally good, with only very slight signs of the Parkinson symptoms of speech inhibition and freezing.

As regards the 2 symptoms I still have, I can only agree with the finding in the last line and confirm it without reservation.

As regards the subject of research using adult stem cells, I have corresponded in writing with people including reputable scientists from organizations such as the FRAUNHOFER Institute.
As a rule, their answers are:

1. It has not been sufficiently tested.

2. Therapy with adult stem cells generates tumors.

3. Total rejection.

My answer, in part from experience:

1. How can it be tested if it is rejected out of hand?

2. Even doctors/professors don’t know everything. Therapy with adult stem cells does not generate tumors (see /news/stem-cells-and-tumor-risk.aspx ).

3. Because they are sponsored by the pharmaceutical industry and haven’t undergone further training.

The fact is:

· Sick people hope, o n l y the XCell-Center helps!

· The leading doctors and the management responsible for stem cell therapy in the XCell Center do not guarantee the successful treatment of any patient.

· Even though I still have 2 mild symptoms, the elimination of all others has significantly improved my quality of life.

· I personally am very satisfied with the treatment and the result.

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Regenerative Medicine Treatment Process

XCell-Center, Cologne, Germany

The entire process of our stem cell treatment

Patients initially apply for treatment by e-mail or phone. We then explain what stem cell therapy could mean for them and the requirements that have to be met before they can undergo therapy. The next step involves the patient sending his or her medical records (diagnosis and recent blood tests) to the XCell Center. A multidisciplinary team then reviews the patient’s medical status and decides whether stem cell therapy will be possible and appropriate.

If stem cell therapy is an option, a detailed treatment plan is prepared and the patient is informed of the costs of treatment, which vary depending on the type of treatment necessary. Once the patient has consented to the treatment plan and costs, an appointment is scheduled for bone marrow extraction. Please note that this is a surgical procedure, so it is important that patients do not take any blood-thinning medication in the ten days prior to the appointment. It is necessary for the patient to consult their own doctor before discontinuing this type of medication.

The treatment procedure

1. Bone marrow extraction

2. Isolation, analysis and concentration of the stem cells in the laboratory

3. Stem cell implantation

4. Postoperative care

The entire procedure is performed in compliance with the principles of “Good Manufacturing Practice” and in accordance with the latest technological and medical standards. The risks associated with adult stem cell therapy are low. They are no different from the risks normally associated with surgical procedures. The therapy involves the use of the patient’s own cells, so the risk of rejection –as there would be in a cell or organ transplant procedure– is almost nil.

Patients travelling from abroad to Cologne for stem cell therapy are met by an XCell Center employee at the airport or train station and accompanied to their hotel or to the institute. Generally, our patients do not require round-the-clock care, so they stay in a hotel for the duration of their treatment. The transfers from the hotel to the institute and back are organized by the XCell Center.

Bone marrow extraction

Bone marrow is extracted from the hip bone by one of our physicians. This procedure normally takes around 30 minutes. First, local anesthetic is administered to the area of skin where the puncture will be made. Then, a thin needle is used to extract around 150-200 ml of bone marrow. The injection of local anesthetic can be slightly painful, but the patient barely feels the extraction of bone marrow. Once the bone marrow has been extracted, the patient may return to his or her hotel.

Another method of stem cell extraction involves the mobilization of bone marrow stem cells with the assistance of growth factors. The growth factors are injected into the patient and cause the stem cells from the bone marrow to enter the bloodstream. Stem cells can then be isolated from a blood sample. The XCell Center uses this method less frequently, though in some cases it is a good alternative to bone marrow collection.

Isolation, analysis and concentration of the stem cells in the laboratory

The quality and quantity of the stem cells contained in the collected bone marrow are tested in one of our laboratories. First, the stem cells are isolated. Then a chromatographical procedure is used to separate them from the red and white blood corpuscles and plasma. The sample is tested under sterile conditions so that the stem cells which will be administered to the patient cannot be contaminated with viruses, bacteria or fungi. The sample is also tested for the presence of viral markers such as HIV, hepatitis B and C and cytomegalia. The entire process is documented and the concentrated stem cells are not released for administration until all quality criteria have been satisfied.

The cleaned stem cells are counted and vitality checks are made. If there are enough vital stem cells, i.e. more than two million CD34+ cells with over 80 percent vitality, the stem cell concentrate is approved for patient administration. The cells are stored in liquid nitrogen at -196 degrees Celsius until it is time for them to be used.

Stem cell implantation

The method of stem cell implantation depends on the patient’s condition. There are four different ways of administering stem cells:

· Intravenous administration

· Administration via catheter using angiography

· Administration via lumbar puncture

· Direct injection into the target area by way of surgery

To treat diabetic feet, the stem cell concentrate can be injected directly into the diseased tissue.

Intravenous administration

Intravenous administration is the most straightforward method. It is used if the cells have to be distributed throughout the entire body. One disadvantage of this method is that the concentration of cells arriving at the target organ is relatively low. This is why intravenous administration is generally combined with other methods. It is suitable for patients with vascular diseases, strokes, spinal cord injuries, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease.

Angiography

Angiography facilitates the direct administration of stem cells to the target organ. A catheter is inserted into the femoral artery under local anesthetic. A radiologist is on hand to ensure that the catheter is pushed forward precisely to the target organ – e.g. liver, heart or pancreas – where the stem cells are to be delivered. This procedure takes around one and a half hours. After angiography, the patient is monitored at the clinic for several hours before returning home. Angiography is used when patients have diabetes mellitus in order to deliver the stem cells straight to the pancreas, or for patients who have had a cardiac arrest or suffer from cardiac insufficiency (weak heart).

Lumbar puncture

The stem cells can also be administered by lumbar puncture into the cerebrospinal fluid in patients with neurological diseases such as Alzheimer’s or multiple sclerosis. They are injected between the vertebra at the lumbar vertebra level. There is no spinal cord here, so it cannot be damaged through the treatment. The spinal canal contains cerebrospinal fluid. Since cerebrospinal fluid circulates, the stem cells are transported directly to the damaged tissue in the spinal cord or brain. Lumbar puncture is performed under local anesthetic.

Lumbar puncture is also suitable for patients who cannot undergo angiography as a result of a blocked artery or patients who are at a high risk of hemorrhaging. This method of application is very safe. Adverse effects such as headaches and nausea may occur, but are only temporary.

Surgery

Direct injection of the stem cell concentrate into the diseased tissue facilitates the administration of the maximum concentration of cells. Depending on the region being treated, surgery can involve a general anesthetic and a several-day stay at the institute.

When treating a spinal cord injury, a laminectomy is performed under general anesthetic. This involves opening the affected vertebra and the dura. The stem cells are then injected directly into the damaged tissue with a small needle. The dura and vertebra are then closed and the operation is finished. Patients usually have to stay in the clinic for two to three days after this operation.

The treatment of a stroke patient involves the administration of the stem cells directly into the affected region of the brain. The procedure is performed under local anesthetic via a tiny hole in the skull. A neuro-navigation system then guides a catheter into the infarcted area. It calculates the precise route to the target area, which minimizes the risk of damaged blood vessels. After the procedure, the wound is closed and after only a few days it is invisible. The patient remains in the clinic overnight for monitoring, and is then discharged on the following day.

Information about the risks of surgery

A surgical procedure is always associated with certain risks and side-effects. These include risks relating to the anesthetic and infections, complications when the wound is healing and temporary post-surgical pain. In rare cases, temporary epileptic seizures may occur after brain surgery. Bleeding can also occur on rare occasions. The XCell-Center minimizes surgical risks by using state-of-the-art medical equipment and ensuring strict adherence to hygiene regulations.

Postoperative care

The majority of patients is not negatively affected by stem cell therapy and can normally leave the XCell-Center a few hours after the implantation procedure. Patients who undergo surgery usually stay for one, two or three days in the clinic.

There is a 24-hour patient hotline in case patients have any queries after they have been discharged. The patients also stay in contact with their physician or a patient consultant by telephone or e-mail so that the XCell-Center can monitor their progress. For example, this enables the modification of insulin dosage after stem cell therapy, and the institute is able to provide patients with recommendations for their further rehabilitation.

Adult stem cells

Undifferentiated cells (these include the various types of multipotent and unipotent stem cells), found in a differentiated tissue of the developed, adult organism. These cells can renew themselves and differentiate (with certain limitations) to give rise to all the specialized cell types of the tissue they derive from. Adult stem cells can be found in bone marrow or in the umbilical cord blood of newborn babies.

Bone marrow stem cell

Multipotent stem cells from bone marrow; types include haematopoietic stem cells and mesenchymal stem cells.

CD34-positive cells

CD34 refers to a special molecular structure that can be found on the surface of haematopoietic stem cells. With the help of this marker, the haematopoietic precursors can be differentiated from other precursors. CD is the abbreviation of “cluster of differentiation”.

Cell-based therapies

See: Regenerative medicine

Clone

To generate identical copies of a molecule, cell, or organism.

Cord blood stem cells

The vessels of the umbilical cord during and shortly after delivery contain stem cells. These stem cells are in the blood at the time of delivery, because they move from the liver, where blood formation takes place during foetal life, to the bone marrow, where blood is made after birth. Umbilical cord stem cells are similar to the stem cells that reside in bone marrow, and can be used for the treatment of leukaemia and other diseases of the blood.

Differentiation

The process whereby an undifferentiated embryonic cell acquires the features of a specialized cell such as the liver, brain, heart or muscle cell.

Embryo

The product of a fertilized egg. This term extends from the time of fertilization (zygote) until it becomes a foetus, which in the human is approximately eight weeks later.

Good Manufacturing Practice

“Good manufacturing practice” (GMP) is a part of quality management. It guarantees that products are constantly produced and checked according to the highest quality standards underlying the licence documents or the product specification. Good manufacturing practice is concerned with production as well as quality control. A company gets a manufacturing licence if all stages of production and control are carried out in accordance with the basic rules of good manufacturing practice.

Haematopoietic stem cell

Precursor of mature blood cells

In vitro

Latin for “in glass”. Names processes that take place or are done in a laboratory dish, test tubes or other artificial environments.

Mesenchymal stem cells

Also known as bone marrow stromal cells. Mixed group of cells from the non-blood-forming section of bone marrow. Mesenchymal stem cells are capable of growth and differentiation into a number of different cell types.

Multipotent

The ability of an individual stem cell to develop into only a limited range of cell types. In general, adult stem cells are multipotent. Also see pluripotent and totipotent.

Plasticity

The ability of stem cells from a particular type of tissue to give rise to cell types of another type of tissue.

Pluripotent

The ability of an individual stem cell to develop into numerous other types of cells. In general, embryonic stem cells are pluripotent.

Regenerative medicine

A treatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cell populations.

Stem cells

Cells with the ability to divide for indefinite periods in culture and to give rise to specialized cells.

Tissue Engineering

Tissue Engineering refers to the production of tissue constructions from endogenous somatic cells. Stem cells or other differentiated somatic cells are used for the construction. In this way, tissue (such as skin or cartilage) can be grown outside the body and then transplanted to the patient.

Totipotent

Type of cell that can form an entire organism. The zygote (a fertilized egg) and the first four cells produced by its cleavage are totipotent.

Unipotent

Usually applied to cells in adult organisms that are capable of differentiating along only one lineage.

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Skin transformed into stem cells

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Japanese researchers created pluripotent cells

Human skin cells have been reprogrammed by two groups of scientists to mimic embryonic stem cells with the potential to become any tissue in the body.

The breakthrough promises a plentiful new source of cells for use in research into new treatments for many diseases.

Crucially, it could mean that such research is no longer dependent on using cells from human embryos, which has proved highly controversial.

The US and Japanese studies feature in the journals Science and Cell.

Until now only cells taken from embryos were thought to have an unlimited capacity to become any of the 220 types of cell in the human body – a so-called pluripotent state.

But campaigners have objected to their use on the grounds that it is unethical to destroy embryos in the name of science.

In the US only limited use of embryonic stem cells is allowed by scientists receiving public funding.

The Japanese team used a chemical cocktail containing just four gene-controlling proteins to transform adult human fibroblasts – skin cells that are easy to obtain and grow in culture – into a pluripotent state.

The cells created were similar, but not identical, to embryonic stem cells, and the researchers used them to produce brain and heart tissue.

After 12 days in the laboratory clumps of cells grown to mimic heart muscle tissue started beating.

The US team, from the University of Wisconsin-Madison, achieved the same effect by using a slightly different combination of chemicals.

They have created eight new stem cell lines for potential use in research.

Cloning superceded

Using skin cells should mean that treatments could be personalised for individual patients, minimising the risk of rejection.

Not only does the new technique remove the need to create embryos in the lab, it is also more simple, and more precisely controlled than current cloning technology.

Professor Ian Wilmut, of the University of Edinburgh, who led the team which created Dolly the sheep in 1996, has said it represents a significant advance.

However, the researchers have warned more work is needed to refine the process, and ensure its safety.

At present both techniques rely on viruses to introduce new material into the cells, which carries a potential risk of contamination.

Researcher Professor James Thomson said: “The induced cells do all the things embryonic stem cells do.

“It’s going to completely change the field.”

Dr Shinya Yamanaka, of Kyoto University, a member of the Japanese research team, said: “These cells should be extremely useful in understanding disease mechanisms and screening effective and safe drugs.”

Positive reaction

Professor Azim Surani, of the University of Cambridge, said the research should allow scientists to create a large range of human stem cell types, which could prove invaluable in studying disease.

He said: “It is relatively easy to grow an entire plant from a small cutting, something that seems inconceivable in humans.

“Yet this study brings us tantalisingly close to using skin cells to grow many different types of human tissues.

Dr Lyle Armstrong, of the International Centre For Life at the University of Newcastle Upon Tyne, called the studies a “major development”.

He said: “Although it is early days for this technique it may well prove to be every bit as significant as the first derivation of human embryonic stem cells nine years ago.”

Professor Robin Lovell-Badge, of the Medical Research Council’s National Institute For Medical Research, said the work was exciting, but work was required to end the reliance on viruses, and to tease out why two different techniques produced similar results.

Josephine Quintavalle, of Comment on Reproductive Ethics, said: “News that embryonic stem cells can be created successfully from human cells without cloning, without using human embryos or human eggs, or without getting involved in the creation of animal-human embryos, is most warmly welcomed.

“We congratulate these world-class scientists who have had the courage to state their change of tack so cogently.

“For once we have better science coinciding with better ethics.”

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