Thursday, October 16, 2008
Thu Oct 16, 5:47 PM
By The Canadian Press
TORONTO - Canadian and Japanese stem cell researchers are joining forces in a bid to more quickly translate scientific discoveries from the lab into treatments for people with such diseases as autism and cystic fibrosis.
The University of Toronto and Japan's Kyoto University signed a research-sharing agreement in Tokyo on Thursday that will bring together world-renowned stem cell researchers in Toronto with the Japanese lab of Dr. Shinya Yamanaka.
Yamanaka shook the science world last year by converting normal adult cells into embryonic-like stem cells.
Embryonic stem cells have the ability to differentiate into any type of tissue in the body, from heart and liver to brain and skin. But the idea of harvesting stem cells from human embryos is ethically contentious.
Yamanaka's discovery would allow scientists to get around restrictions regarding generation of stem cells from embryos, meaning research should move at a faster pace.
"Shinya Yamanaka and his team have developed some of the world's most important technology in stem cell research, and the team at U of T is among the best at differentiating cells to produce innovative therapies," Bill Stanford, associate director at the university's Institute for Biomaterials and Biomedical Engineering, said in a statement.
"Together, we'll share patient samples, technologies and protocols to get basic science to the clinic much faster."
The collaboration should greatly speed up development of drug therapies, said Stanford, who believes cell-replacement therapy also will be a reality in the not-too-distant future.
"We are already known as one of the best places in the world for stem cell research because of our genetic diversity, unique medical system and concentration of top-notch scientists ... and it will certainly bolster home-grown opportunities for commercialization."
By TIM MARTIN, Associated Press Writer Tim Martin, Associated Press Writer Mon Oct 13, 4:56 am ET
LANSING, Mich. – Michigan voters will be thrust into the crossroads of science, ethics and religion next month when they decide whether to loosen the state's restrictions on embryonic stem cell research.
Supporters of the ballot measure say it could put Michigan researchers at the forefront of an emerging science that might help discover cures for spinal cord injuries, diabetes, Alzheimer's and a host of other illnesses.
Opponents say the research is unethical because it involves the use and destruction of human embryos. The groups Michigan Catholic Conference and Right to Life of Michigan are among the proposal's opponents.
Many scientists believe embryonic stem cell research holds more promise for medical breakthroughs than less controversial adult stem or umbilical cord blood research. Embryonic stem cells are more versatile.
"Maybe not in my lifetime, but eventually, the majority of therapies and cures will be coming from genetic therapy," said Joe Schwarz, 70, a doctor and former Republican congressman from Michigan who chairs the pro-ballot CureMichigan campaign.
Michigan's current stem cell laws are among the nation's most restrictive. Some embryonic stem cell research is allowed in Michigan, but only on stem cell lines already established by researchers in other states.
The stem cell measure, on the ballot as Proposal 2, would change state law to allow people to donate embryos left over from fertility treatments. Those embryos, not suitable for implantation, would otherwise be thrown away as medical waste.
An opposition group says the proposal would take away Michigan lawmakers' ability to regulate the emerging discipline.
"There are a lot of reasons to vote 'no' on this, and one is that it would lead to unregulated research," said David Doyle, a spokesman for an opposition group called Michigan Citizens Against Unrestricted Science and Experimentation.
Supporters counter that research using human embryos is regulated by federal law. And the proposal spells out some other limitations that would be specific to Michigan.
The embryos would have to be donated. Buying or selling human embryos for the research would be illegal. Stem cells couldn't be taken from embryos more than 14 days after cell division begins.
The measure takes on added significance because of possible upcoming changes to federal law.
President Bush restricted the use of federal money going to embryonic stem cell research. But both Republican John McCain and Democrat Barack Obama have said they support relaxing federal restrictions.
That could result in more grant money and life sciences jobs in states prepared to capitalize on the changes. California, for example, already plans to invest $3 billion on the research.
A study done for the Michigan Prospect, a Lansing-area think tank with several Democratic directors, suggests that even a 1 percent boost in biotech employment from stem cell research would lead to more than 400 new biotech jobs, not counting potential spinoff jobs. It estimates a 5 percent boost in biotech employment would bring more than 2,000 jobs.
Stem cell ballot battles are relatively rare in other states.
In 2006, Missouri voters approved an amendment protecting stem cell research by a narrow margin, 51 percent to 49 percent. Efforts to undo the proposal began almost immediately, although the counterproposals did not make the 2008 ballot.
In Florida, two competing stem cell proposals failed to make the ballot this year. One proposal would have banned state funding of embryonic stem cell research, while the other would have required the state to provide $20 million a year for such research.
On the Net:
Pro ballot: http://www.curemichigan.com
Wednesday, October 15, 2008
Fri Oct 10, 5:46 pm ET
WASHINGTON (Reuters) – Japanese researchers who invented a way to make powerful stem cells out of ordinary cells say they have now found a safer way to do it.
Shinya Yamanaka of Kyoto University in Japan and colleagues invented a new way to transform ordinary cells into embryonic-like stem cells called iPS cells, using a ring of genetic material called a plasmid.
Working in mice, they generated induced pluripotent stem cells, or iPS cells, and said they believe the method can work in people, too, and is an important step toward a new field called regenerative medicine.
Stem cells are the body's master cells, giving rise to all the tissues, organs and blood. Embryonic stem cells are considered the most powerful kinds of stem cells, as they have the potential to give rise to any type of tissue.
But they are difficult to make, requiring the use of an embryo or cloning technology. Many people also object to their use, and several countries, including the United States, limit funding for such experiments.
In the past year, several teams of scientists have reported finding a handful of genes that can transform ordinary skin cells into iPS cells, which look and act like embryonic stem cells.
To get these genes into the cells, they have had to use retroviruses, which integrate their own genetic material into the cells they infect. This can be dangerous and can cause tumors and perhaps other effects.
Last month U.S. researchers did the same thing using a harmless virus called an adenovirus, but the method was not efficient -- and introducing any virus into the body can pose risks.
Yamanaka's team tried several different methods but eventually looped three of the genes needed into one plasmid and the fourth into another, and transplanted these into cells from a mouse embryo.
The mouse embryonic cells reverted to a stem-like state and began behaving like embryonic stem cells.
Yamanaka's team said the method was also not as efficient as using retroviruses but said they plan to try their method using human cells.
If it works, some day doctors may be able to make tailor-made transplants to treat diseases in people by removing a few cells, transforming them in the lab and transplanting the new tissue or organs back in.
Copyright © 2008 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.
Copyright © 2008 Yahoo! Inc. All rights reserved.
Tuesday, October 14, 2008
LOU GEHRIG’S DISEASE DEMONSTRATION!TUESDAY, NOVEMBER 11, 200810AM to 4PM U.S. Capitol Building West Front Lawn (handicapped accessible), WASHINGTON ,
LOU GEHRIG’S DISEASE DEMONSTRATION!
TUESDAY, NOVEMBER 11, 2008
10AM to 4PM
U.S. Capitol Building West Front Lawn (handicapped accessible), WASHINGTON , D.C.
ALS Patients Protest Legal Dispute Preventing Access to Life-Saving Drug
GENENTECH-TERCICA*-INSMED: RELEASE IPLEX NOW!
Support patients with Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease) now by joining our demonstration to force Genentech, Tercica and Insmed to resolve their legal dispute and release IPLEX to provide symptom relief for this horrible disease. We are calling on all persons with ALS, caregivers, friends, family, media and others to join us in protesting this devastating travesty of justice.
IPLEX is a biomedical pharmaceutical that reduces the symptoms for ALS patients and provides significant relief and improvements, a previously unheard-of achievement although not specifically developed for that purpose. Despite that, on March 7, 2007, a settlement agreement between Genentech, Tercica and Insmed removed IPLEX from ALS patients in the US and throughout the world, with the exception of Italian ALS patients, a cruel settlement exclusion. While Italian ALS patients benefit from IPLEX, the rest of the ALS world suffers debilitation, deprivation and death.
IPLEX is an improved version of Increlex, a drug originally intended to improve severe short growth stature. While both drugs accomplish that to a greater or lesser degree, only IPLEX signif icantly improves the quality of life for ALS patients. Despite that, persons with ALS lost access to IPLEX and are offered Increlex. After many months of usage, it is clear that IPLEX is the only drug that offers the greatest possible benefit to ALS patients. Nevertheless, it remains unavailable due to the greed of Genentech, Tercica and Insmed, all of whom agreed to this immoral settlement agreement in the name of corporate and personal profit.
Attempts to procure IPLEX have failed, despite continuous contact with the CEO’s of all three corporations, media, judiciary, attorneys, Senators, Representatives and other government officials. Each blames or points to the other. No one takes responsibility for this travesty.
Public demonstration is now the only recourse left to the ALS community.
ALS robs its victims of all voluntary muscles, sentencing its victims to what is called “a brief life in a glass coffin” and death within 2 to 4 years. IPLEX is the only drug yet developed that significantly slows and in some cases reverses this devastating disease.
Our hope is this demonstration will alert the public, our congress and the media to help force Genentech, Tercica and Insmed to release IPLEX. Join us in this critical effort. Help make IPLEX available to ALS patients to improve the quality of their lives, for however long that is.
Scientific and demonstration activity details are attached. For further information, please contact:
Andrea Reimers, RN
Sunday, October 12, 2008
10/10/2008TAIZHOU, Jiangsu, CHINA, Oct. 10 /Xinhua-PRNewswire/ -- Beike Biotechnology Co. Ltd., ( http://www.beikebiotech.com/ ) a global leader in stem cell research and treatment through evidence-based medicine, announced today it has signed eight separate mutual cooperation agreements with some of China and the world's most outstanding stem cell research organizations. As part of the agreements, Beike has also established a "Stem Cell Expert Advisory Committee" and a separate "Data and Safety Monitoring Board (DSMB)" to oversee future Beike-sponsored research.The eight accords, initially discussed at the recently completed 2008 China Stem Cell Technology Forum held at China Medical City, will deepen Beike's leadership in providing safe, effective, and cutting-edge stem cell treatments to patients from all over the world. The eight organizations that will share resources, research information, and best practices with Beike Biotech are: AELCELL of Stanford, California, Nanjing Medical University, the China Medical City, Hua Zhong Technical University, the University of Texas Health Science Center at Houston, Jiangsu People's Hospital, the No. 2 Hospital of Nanjing Medical University, and the Wu Hu City No. 2 People's Hospital in Anhui, China. These mutual cooperation agreements vastly increase Beike's ability to incorporate real-time research information into its network, bolstering Beike's position as the Asian leader and one of the world's foremost biotechnology companies providing stem cell solutions for a range of ailments.Dr. Sean Hu, the Chairman of Beike Biotech, stated, "Beike realizes there is definitely strength in numbers when it comes to discovering the latest and best stem cell technologies that will effectively fight a range of terrible diseases. Therefore, we are extremely enthusiastic to be cooperating with eight of the world's leading stem cell research centers, so that together we can more rapidly bring effective treatments to those who need it today."On the sidelines of the Forum, Beike also sought out a number of highly respected doctors from China and abroad to serve on a newly established "Data and Safety Monitoring Board (DSMB)" that will oversee Beike-sponsored stem cell research. The DSMB, which is Chaired by Dr. Li Zhanquan of China's Liaoning People's Hospital and includes Dr. Geng Yongjian of the University of Texas Medical School, will operate in line with the spirits of the Declaration of Helsinki, the Council of International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects, and Guidelines for Good Clinical Practice from the World Health Organization (WHO) and The International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. Members of the DSMB will review data protocols and enforce stringent, international safety standards for specific clinical trials Beike plans to conduct this year.Additionally, a "Stem Cell Expert Advisory Committee" was established from among China's top science institutions to provide advice to Beike on ethical issues covering basic and clinical stem cell research, as well scrutinize clinical trial project teams for sound data monitoring and best safety practices. The five rotating Members of the Stem Cell Expert Advisory Committee, which initially include Dr. Wang Zhonggao of the prestigious Chinese Academy of Sciences and Dr. Chen Hao Zhu of the China Engineering Academy, will provide guidance on ethical issues and scrutinize clinical trials for safety monitoring, also adhering to all international protocols stated above such as Helsinki, CIOMS, WHO, and ICH.Dr. Sean Hu further said, "We at Beike are committed to providing clarity and resonance in the newly unfolding stem cell research and treatment fields. We seek to set the global standard, demonstrating that everything we do is genuine, safe, and of world-class quality. This is why we will continue to increase transparency, welcoming international standard oversight systems which will serve to make the Beike team and our services even better."About Beike Biotechnology Company LimitedBeike is a biotechnology company founded in July 2005 with capital from Beijing University, Hong Kong University of Science and Technology and Shenzhen City Hall. That year it commercialized stem cell technology that had been in research since 1999. The research and clinical work comes from collaborations with leading institutions in China including Tsinghua University, Beijing University, Hong Kong University of Science and Technology, No. 3 Army Medical University, Zhongshan Medical University, Guiyang Medical College and Zhengzhou University. Over 250 patients each month are treated with Beike's stem cells in leading hospitals throughout China. Patient experiences from treatments can be found at Stem Cell China News ( http://www.stemcellschina.com/ ).
Thursday, October 9, 2008
Wed Oct 8, 1:59 AM ET
The University of Minnesota has concluded that falsified data were used in a 2001 article published by one of its researchers on adult stem cells. The school is asking that the article be retracted.
The conclusion follows an 18-month investigation into research published by stem-cell expert Dr. Catherine Verfaillie. The investigation clears Verfaillie of misconduct but points to a former graduate student, Dr. Morayma Reyes, who is now an assistant professor at the University of Washington.
The university blames Verfaillie for "inadequate training and oversight," and says it has asked for a retraction of the published article, which appeared in the journal Blood.
Reyes said it was an honest error and there was no intent to deceive.
The study was one of a series that Verfaillie published, suggesting that adult stem cells could be used as an alternative to embryonic stem cells in medical research.
Her research received international attention because of political and ethical controversies over research involving embryonic stem cells. A panel of experts concluded that four images used in the Blood paper were intentionally altered, according to Tim Mulcahy, the university's vice president of research.
Verfaillie, who now lives in Belgium, could not be reached for comment, the Star Tribune reported.
Reyes, who responded to questions by e-mail, said the correction in the journal Blood is warranted. However, she denied falsifying data.
She said the university panel said she falsified data by adjusting brightness and contrast in scientific images included in the article. At the time the research was done, that was an accepted practice but it has since changed, she said. The panel judged her on the newer standard.
Reyes said the errors occurred because of "inexperience, poor training and lack of clear standards" on the handling of digital images. "I regret very much these errors and never had the intention to deceive," she said.
But Reyes also said they in no way altered the conclusions of the paper, and the research has since been successfully reproduced by other scientists.
Mulcahy said it's not clear how, or if, the discovery will affect the underlying findings of the research. "That's an issue that ultimately the scientific community will have to resolve for itself," he said.
Tuesday, October 7, 2008
By Devon Williams(EP News)--Across the country and around the world, adult stem cells are showing promise for a variety of diseases.Researchers at the University of Wisconsin have injected a rat with modified bone-marrow stem cells to strengthen its muscles and their connecting nerves. Scientists are hopeful this will provide treatment for Lou Gehrig’s disease, which currently has no cure.Researchers at Texas A&M have discovered that bone-marrow stem cells injected into the brains of mice can repair stroke damage. They also demonstrated that adult stem cells can help prevent brain damage.“Stroke is the third leading cause of death in the U.S. ,” said David Prentice, senior fellow for life sciences at the Family Research Council. “This result, and the mechanism uncovered for adult stem cells, could lead to significant treatments not only for stroke and other brain disorders, but also for diseases and injuries to other tissues throughout the body.”And in Kyoto , Japan , researchers have discovered that adult stem cells present in the brains of mice continue to produce new brain cells that are important for memory and learning. The discovery may be able to help human patients who suffer from memory loss.
Sunday, October 5, 2008
Dear Brothers and Sisters,
We are asking for your assistance in this David vs. Goliath battle against the forces that have denied PALS (patients with ALS) access to the therapeutic Iplex.
Team Iplex has decided to bring our case to Washington, DC. We are in the process of organizing & coordinating a peaceful demonstration to protest and create awareness of this particular travesty of justice. We have decided to expose the triumvirate of Genentech/Tercica/Insmed and their official & immoral philosophy of profits over human life.
What we are asking is that you join us on our 11/11/08 peaceful protest in Washington, DC. As we all know, there is strength in numbers. With your help and involvement, we will be able to apply the very much needed pressure, which will once and for all, gain the release access of Iplex into the hands of PALS.
After several attempts to get straight answers out of the principals in this patent dispute, we have slowly come to the realization that the triumvirate of Genentech/Tercica/Insmed does not care about our right to live. We believe the time to stop sitting by silently has come to an end.
What we will be demanding is that all three - Genentech/Tercica and Insmed - come to the table and develop an immediate agreement to facilitate a release of Iplex. All we want is the same opportunity that Genentech/Tercica/Ismed has given to PALS in Italy.
Better said, we want the same opportunity and chance at life as those that are dying and suffering from ALS in Italy. End of story!
The bottom line is that we can't continue to stand around waiting. Not with ALS!!! We've already tried asking; that simply doesn't work. It's time to start demanding our right to life, our right to a therapeutic. What Team Iplex is proposing has already been done successfully by Italian PALS. I say if we come up short in our mission, we try again in six months. The only way we can possibly lose is by giving up. Brothers and Sisters, how on earth do we possibly expect different results from the same methods? So at least for two or three days, let's get off the ALS forums and get together in Washington, DC. What have we got to lose?
Please help our effort to help ALL PALS obtain a therapeutic.
Please Contact One of the Team Leaders about the Details.
Andrea Vaughn, California
Debbie IPLEX, New Jersey
Eddie Esparza, Chicago
Eric Fox, Michigan veterans)
Guy IPLEX Chicagoland)
John Citron IPLEX
Kathy T work IPLEX
Steve Byer, Wisconsin)
Virginia Schoenfeld, Military Liaison)
A placebo-controlled trial of insulin-like growth ...[Neurology. 1998] - PubMed Result.url (284b), Allow IPLEX to be distributed to ALS patients.url (201b), ALS patient denied access to drug.url (305b),
ALSTDI Forum - IPLEX- letter from italian forum.url (251b),
Beneficial effects of intrathecal IGF-1 administra...[Neurol Res. 2005] - PubMed Result.url (286b),
chicagoreader.comfeaturesstoriesourtown080717.url (287b), Director Eva L. Feldman, M.D., Ph.D..url (197b),
Effects of Insulin-Like Growth Factor-1Binding Protein-3 Complex on Muscle Atrophy in Rats.url (213b),
Efficacy and safety of mecasermin rinfabate. [Expert Opin Biol Ther. 2006] - PubMed Result.url (250b),
Glycosaminoglycans co-administration enhance insul...[Int J Dev Neurosci. 2000 Jul-Aug] - PubMed Result.url (566b),
Growth factor stimulates rapid extension of key motor neurons in brain.url (296b), Growth of spinal nerves is improved [Archive] - CareCure Forums.url (277b),
IGF-1 Role Adds to Understanding of Nerve Cell Development and, Perhaps, Repair.url (221b), IGF-I specifically enhances axon outgrowth of corticospinal motor neurons - Nature Neuroscience.url (274b),
Insmed Presents Positive IPLEX(TM) Data At ENDO 2006 - Health - redOrbit.url (418b), Insmed Provides Update On IPLEX(TM) Expanded Access Program In Italy For The Treatment Of Amyotrophic Lateral Sclerosis.url (4KB),
Insmed reports positive results for Iplex in HARS - Pharmaceutical Business Review.url (327b), Insulin-like growth factor delivery across the blo...[Chemotherapy. 2006] - PubMed Result.url (286b),
Insulin-Like Growth Factor System in Amyotrophic Lateral Sclerosis.url (332b),
Insulin-like growth factor-I for the treatment of amyotrophic lateral sclerosis - Amyotrophic Lateral Sclerosis.url (354b),
Iplex (Mecasermin Rinfabate [rDNA origin] Injection) clinical pharmacology - prescription drugs and medications at RxList.url (259b),
Ipsen, an innovation driven international specialty pharmaceutical group.url (363b),
MyotonicDystrophy Message Hello Its me im back.url (316b),
Recombinant human insulin-like growth factor I (rh...[Cochrane Database Syst Rev. 2002] - PubMed Result.url (286b),
Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosismotor neuron disease..url (686b),
Retrograde viral delivery of IGF-1 prolongs surviv...[Science. 2003] - PubMed Result.url (286b), Retrograde Viral Delivery of IGF-1 Prolongs Survival in a Mouse ALS Model -- Kaspar et al. 301 (5634) 839 -- Science.url (272b),
rhIGF-IrhIGFBP-3) In Myotonic Dystrophy.url (377b),
Statement Regarding Requests to Make IPLEX.url (177b),
Team Iplex Web Site - Give-Us-Iplex.Blog.com.url (2KB),
Tercica — On the Horizon.url (199b),
The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain -- Russo et al. 26 (7) 916 -- Endocrine Reviews.url (211b),
Therapeutic benefit of intrathecal injection of in...[J Neurol Sci. 2005] - PubMed Result.url (608b), Translated version of http--www.carlobruno.it-.url (850b), www.indestructiblefilm.com.url (171b),
Yahoo! Message Boards - Insmed Incorporated - Physician Request for a Single Patient IND for Compassionate or Emergency Use.url (598b),
Yahoo! Message Boards - Insmed Incorporated - Re Class-action lawsuit ......url (444b)
Thursday, October 2, 2008
We are excited to let you know that The ALS Association achieved another victory in Washington this week when the President signed into law the FY 2009 Department of Defense Appropriations bill. For the first time, Congress included $5 million in the bill to fund the ALS Research Program (ALSRP) at DOD! We now have a congressionally established program at the DOD that is dedicated solely to ALS research. It is the only ALS specific program at the DOD and is the only program focused on translational research with the goal of finding new treatments for ALS. This is an especially significant victory not only because very few funding bills even passed Congress this year, but also because we overcame a significant amount of competition for scarce federal dollars. The $5 million we secured will be available to ALS researchers across the country. Moreover, the collaboration facilitated by the ALSRP and the additional dollars will provide the ALS community with greater opportunities to develop meaningful treatments. Funding Continues Critical Partnership with DODWhile this is the first time Congress has ever provided funding for the ALSRP, the program was initially developed last year when The Association partnered with DOD to bring new focus to their ALS research portfolio, which we originally helped to start more than five years ago. Dr. Lucie Bruijn, The Association's Sr. Vice President of Research and Development, and Ellyn Phillips, President of the Greater Philadelphia Chapter and Chair of the Association's Board of Trustees Advocacy Committee, served on the ALSRP peer review committee and the program itself was modeled after our TREAT ALS program. Additionally, we successfully worked with the DOD earlier this year to nominate ALS Association Trustee Diane Winokur as a patient/family representative advising the ALSRP on the impact research proposals may have on patients and families.We look forward to continuing our strong partnership with DOD in 2009 to advance ALS research and find a treatment. Thank You!This achievement is the result of the efforts of ALS Association Chapters, PALS, families and military veterans to reach out to Congress and tell the ALS story. It also demonstrates the effectiveness of our strategic outreach, which began when the President released his budget last February and continued through Advocacy Day and the rest of the year.
For the third time in the past two weeks, we have succeeded in accomplishing one of our top priorities. Passage of the ALS Registry Act, implementation of historic new regulations for veterans with ALS, and now funding for ALS research could not have been accomplished without the active involvement of the entire ALS community. THANK YOU!!
Join the Roll Call of Veterans!Veterans with ALS have continued to play an important role in our advocacy efforts. If you are a veteran or know a veteran with ALS, please join the Roll Call of Veterans on our website, here: http://alsa.capwiz.com/alsa/mlm/verify/. Learn how you can help us to continue to advance critical issues that will benefit veterans and the entire ALS community.
If you have any questions, please contact us at email@example.com or 1-877-444-ALSA. Thank You!
Wednesday, October 1, 2008
Researchers Report Stem Cell Advance
By Jeffrey Perkel HealthDay Reporter
Thu Sep 25, 11:47 PM ET
THURSDAY, Sept. 25 (HealthDay News) -- Researchers report that they have sidestepped a major technical hurdle in the generation of pluripotent stem cells from adult cells.
A team of Boston scientists developed a way to generate induced pluripotent stem cells (iPS) -- which are functionally similar to embryonic stem cells, but which can be produced from adult cells, rather than via the creation or destruction of an embryo -- more safely than ever.
Should the findings, which involved mouse cells, be repeated with humans, they could pave the way for using iPS to delve into the biology of a wide range of genetic diseases. Longer term, they could lead to patient-specific stem-cell therapies.
"I think it's a really important, landmark study," said Kevin Eggan, an assistant professor of Stem Cell and Regenerative Biology and an assistant investigator of the Stowers Medical Institute at Harvard University. He was not involved in the study.
The results were published in the Sept. 25 online edition of Science.
Shinya Yamanaka, of Kyoto University, Japan, first demonstrated in 2006 that adult mouse cells -- for instance, skin cells -- could be reprogrammed into something akin to an embryonic stem cell by the introduction of four specific genes. According to the lead author of this latest study, Matthias Stadtfeld, that "was like a gigantic, essentially quantum leap for biology." The following year, Yamanaka and James Thomson, of the University of Wisconsin, Madison, demonstrated the same approach could create human iPS cells.
Normally, the four genes -- all of which can induce cancer if left unchecked -- are delivered using retroviruses, which integrate their viral DNA into the cells' chromosomes; the worry is that these random insertions will introduce mutations into the cells that would alter their behavior, thus minimizing the cells' potential usefulness as research tools. Should these cells ever be used to generate tissues that were transplanted into human patients, researchers fear they could inadvertently lead to cancer.
Konrad Hochedlinger, of Massachusetts General Hospital and the Harvard Stem Cell Institute, his postdoctoral fellow Stadtfeld, and their colleagues circumvented this problem by delivering the genes using adenoviruses instead, which do not insert their viral DNA into a cell's chromosomes. iPS cells generated by this new approach appear indistinguishable from other iPS cells, carry some of the molecular hallmarks of embryonic stem cells, and can form multiple cell types when transplanted into mice (that is, they are pluripotent).
"My conclusion is that viral integration is not necessary for reprogramming to a pluripotent state, which is an important step toward safer patient-specific iPS cells, if it can be translated into humans," said Stadtfeld.
Human iPS cells have several potential applications. On a research level, they may be used to study how particular genetic defects lead to disease. Pharmaceutical companies might be able to use these cells to design drugs that alter, circumvent or repair these behaviors. Ultimately, iPS cells could be used clinically to develop patient-specific transplants, for instance, of genetically repaired neurons in patients with neurodegenerative diseases.
Before any of that can happen, however, this new method must be optimized. Only about one in 1 million skin cells actually developed into an iPS by Stadtfeld's method, compared to one in 10,000 using retroviruses. Using liver cells (hepatocytes), the efficiency was about one in 50,000 -- better, but still worse than with retroviruses.
"For this to be translated into humans, we have to find ways to make the process more efficient and properly make it work in cell types which are more easily accessible than hepatocytes, such as skin cells, for example," said Stadtfeld.
Dr. Rudolf Jaenisch, of the Whitehead Institute and Massachusetts Institute of Technology, who studies iPS cells, called the findings "clearly an advance."
"They show that, although very inefficiently, they can get iPS cells, which apparently don't have any genetic alterations," he said.
Though he praised the study, Eggan noted several caveats. First, though adenoviruses do not normally integrate their DNA into the host cell's chromosomes, sometimes they do. "There's always going to be this lingering possibility that it can happen in some cases," he said.
Yet Eggan also said that, given the success of this study, researchers may ultimately find that they can reprogram adult cells into iPS cells without using viruses at all, for instance, with chemicals or by delivering pure RNAs instead.
"All sorts of things like this become more of a reality due to the success of this experiment," he said.
Eggan's second caveat was that, despite their apparent similarity, iPS cells are not embryonic stem cells. It remains an open question as to whether the two are functionally equivalent.
"There are a variety of fundamental issues which haven't been well addressed about the equivalence of iPS and embryonic stem cells," he said, "I cannot say that strongly enough."
For instance, no one has yet been able to grow a mouse from a single iPS cell -- what Eggan calls the "gold standard" assay of embryonic stem cell pluripotency -- and not for lack of trying, he said.
Questions aside, Stadtfeld said he anticipates no problems translating these findings to human cells, aside from the fact that human embryonic stem cell culture is inherently trickier than its murine counterpart.
"I believe it will be a technical hurdle, but I would expect people would take the hurdle in the next half-year or year -- probably half-year," he said. Then he added, "I think maybe people have taken the hurdle already. It's possible."
For more about stem cells, visit the National Institutes of Health.