Induced Pluripotent Stem (iPS) Cells
Japanese researchers have found that a genetic mutation linked to schizophrenia changes the way brain cells develop and differentiate.
According to a report in today’s Guardian newspaper, the alteration of cell development in the brain changes the normal balance of neurons (nerve cells) and connective tissue in the brain (glia).…
Japanese researchers have found that a genetic mutation linked to schizophrenia changes the way brain cells develop and differentiate.
According to a report in today’s Guardian newspaper, the alteration of cell development in the brain changes the normal balance of neurons (nerve cells) and connective tissue in the brain (glia).
The researchers’ findings, published in Translational Psychiatry, suggest that abnormal neural differentiation leads to fewer neurons and more non-neuronal cells being produced during early stages of brain development, which could be contributing to the presence of the disease.
Dr. Manabu Toyoshima of Japan’s RIKEN Brain Science Institute extracted skin cells from two female schizophrenic patients and two healthy individuals, then reprogrammed them to generate induced pluripotent stem cells (iPS cells), which are like embryonic stem cells in that they have the capacity to differentiate into any cell type in the body.
In essence, the scientists found that the neurospheres (clusters of neural stem cells) derived from the IPS cells of the schizophrenic patients were smaller and produced fewer neurons but significantly more astrocytes — star shaped glial cells.
The findings could help scientists better understand the origins of schizophrenia, a common form of mental illness that affects about one in 100 people and, as the Guardian points out, “is known to be highly heritable, but is genetically complex.”
(This post is one of several addressing a single subject today in a blog carnival to mark the 10th anniversary of the discovery of induced pluripotent stem cells.…
(This post is one of several addressing a single subject today in a blog carnival to mark the 10th anniversary of the discovery of induced pluripotent stem cells. Please click here to read what other bloggers have to say.)
As summer holidays wind down, most parents are now too familiar with the following question: Are we there yet?
Any family trip to a campground, cottage or Nana’s house in Northport starts off with excitement for all concerned, what with getting up early, packing the car and hitting the road. For kids, though, it’s magical. Then, after about an hour of travelling, regardless what onboard entertainment you’ve arranged, boredom sets in. Two hours into the trip, they’re sure you’re never going to get them there.
Waiting for stem cell discoveries to turn into actual treatments is a lot like that, except that instead of hours, it’s decades. Instead of frustration, the feeling is desperation.
Consider the remarkable discovery, by Japan’s Dr. Shinya Yamanaka, that adult cells extracted from skin can be reprogrammed to an embryonic stem-cell-like state to reproduce any cell required for transplant or to repair organs and tissue. We first heard about these induced pluripotent stem cells (iPS cells) on August 25, 2006. A decade later, we’re still waiting for the Nobel Prize-winning work to turn into treatments.
People, especially those suffering from life-threatening diseases, want to know why we’re still waiting. Unlike bored children, they have far more riding on the answer to the Are we there yet? question. For them, it’s life and death.
At the Canadian Stem Cell Foundation hardly a day goes by that someone doesn’t contact us seeking a stem cell treatment for themselves or a loved one. Today, it was a 48-year-old Toronto man whose doctor had told him his ALS will kill him. At least we could point him in the direction of Dr. Eva Feldman at the University of Michigan, who is trying to get a Phase 2 clinical trial going on a stem cell treatment for ALS.
In all areas of medical research, the wheel turns slowly. It can take decades of lab work and clinical trials and hundreds of millions of dollars to bring new treatments to patients. Consider cervical cancer, the second most common cancer among women. In 1972, Germany’s Dr. Harald zur Hausen started working on the notion that the disease is caused by a virus. It took about 35 years — most of his career — for HPV vaccines to make it to market.
It’s even more complicated for stem cells, a relative newcomer to the scene. While their existence was proven in Canada by Drs. James Till and Ernest McCulloch in the early 1960s, the focus afterwards was on bone marrow stem cells for treating leukemia. Embryonic stem cells have only been in play since 1998. Realistically, iPS cells are still the new cells on the block.
Cell-based therapies represent a whole new way of thinking about treating diseases, and regenerative medicine is a disruptive technology. Unlike a vaccine or a drug, the actual therapy isn’t an easy thing to grasp for industry, whose commitment is crucial in moving things from the lab bench to the hospital bed.
What’s needed, then, is an innovative approach. We need to think bigger. That’s why our Foundation is championing the Canadian Stem Cell Strategy, a private/public partnership to deliver up to 10 new curative therapies to the clinic within 10 years. Crafted in consultation with 150 scientists, doctors, leaders from health charities, industry experts and philanthropists, it is backed by an in-depth KPMG study and endorsed by an international panel of experts.
The private sector is already at the table, pledging more than $350 million toward R&D — almost one-quarter of the $1.5-billion Strategy. Other industry partners, health charities and leading Canadian philanthropists are prepared to make major contributions upon demonstration of a federal commitment to the plan. We’re asking the Government of Canada, as part of its Innovation Agenda, to provide one-third, about $50 million annually over 10 years.
Are we there yet? Clearly not. But a coordinated national road map can get us there.
Japan believes regenerative medicine will grow from a $950-million domestic industry in 2020 to a $10 billion one by 2030, according to a report by Bloomberg News.…
Japan believes regenerative medicine will grow from a $950-million domestic industry in 2020 to a $10 billion one by 2030, according to a report by Bloomberg News.
And the Japanese expect to tap into a $120-billion global market over the same time span if regenerative medicine fulfills its potential to set off “a medical and industrial revolution.”
The Bloomberg report illustrates how Japan is building on Nobel Prize winner Dr. Shinya Yamanaka’s discovery of induced pluripotent stem cells (iPS cells) to help recharge its economy. The government has allocated $1 billion in funding and streamlined regulations to expedite the movement of research to the clinic. Meanwhile industrial heavyweights like Fujifilm and Hitachi Ltd. are moving away from fading product lines and diminishing markets to invest in new technology and products using Dr. Yamanaka’s discovery.
“Japan has taken a bold step,” Dr. Hardy TS Kagimoto, who heads the Healios KK biotech firm, told Bloomberg. “It’s been a while since our country has had innovative companies in a global industry that can help us maintain economic power, and we think regenerative medicine can be the one.’’
The powerful iPS cells are made by reprogramming adult skin cells back to an embryonic-like state, a process that circumvents ethical concerns over the use of embryonic stem cells. Beyond transplant purposes, the cells can be used to screen drugs, which Dr Yamanaka believes could “facilitate drug development tremendously.”
Drug regulators in Japan, Europe and U.S. are expected to release coordinated draft drug guidelines for the use of iPS cells in pre-clinical trials by the end of 2017, according to the article, which “could upend the entire market.”
Canada, where stem cells were discovered in the 1960s, is a leader in stem cell research and development but is at risk of losing ground. James Price, President and CEO of the Canadian Stem Cell Foundation (CSCF) recently authored an iPolitics article calling for a comprehensive national approach:
“In order to maintain our position as a global leader in the field that we discovered and pioneered, to help thousands of Canadians and their loved ones who are struggling with life-threatening conditions, and to transform the stem cell sector into a thriving industry built on of high-quality jobs that support families across the country, we need a truly national stem cell effort.”
The CSCF advocates for the Canadian Stem Cell Strategy, an innovative private-public partnership that is the product of consultations with 150 scientists, medical professionals, leaders from major health charities, industry experts and philanthropists. The goal of the Strategy is to deliver up to 10 new therapies in 10 years while helping to grow the Canadian economy and create 12,000 new jobs.
Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.…
Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s premier instalment, we interviewed Dr. Janet Rossant, Chief of Research and a Senior Scientist at The Hospital for Sick Children in Toronto and immediate past president of the International Society for Stem Cell Research. She provided the following highlights.
When I look broadly, I’m seeing a lot of excitement about being able to use stem cells to model human disease. Here in Toronto, we’ve made induced pluripotent stem (iPS) cells from patients with cystic fibrosis, cardiac diseases and autism. We’re beginning to use those cells to differentiate them into different cell types to study the diseases in a Petri dish. All of that is moving forward. We’re going to see more and more of that.
I think, though, that the area to watch is a little bit more than just taking iPS cells and growing them in a Petri dish in a flat culture but instead growing cells and making little organs or “organoids.” We’ve seen over the last year people making little organoids in a dish: gut organoids, stomach organoids. I’m expecting to see papers on lung organoids. This means we will be able to study diseases in new ways and use these organoids for doing drug screening.
We’re also seeing the first trials (by Viacyte, a California-based cell-therapy company) going forward with pancreatic progenitor cells for treating type 1 diabetes. We probably won’t get full results, because these are all Phase 1 trials, but we’re going to get some idea of the survival and effectiveness in a relatively short period of time. Canada will be one of the sites for that trial; Dr. James Shapiro (University of Alberta) is involved.
There have been good Canadian contributions to that. The Viacyte trial is done with pancreatic progenitors that will mature and make the right insulin producing cells. Other people feel you’d be better off starting with the insulin-producing cells and using those directly. A recent paper from Dr. Tim Kieffer (University of British Columbia) shows really good advances in generating functional beta cells. It gives you a lot of hope that this kind of trial, which is an early one, will be rapidly replaced by better trials and better cells. Dr. Cristina Nostro (University of Toronto) is also moving very fast at getting better and better pancreatic islet cells.
The technology that everybody is jumping on is genome editing. Now you can think not only about fixing people with stem cells, but you can think about fixing the genetic defects in people’s stem cells before you put them back. Certainly here at SickKids there are a number of people thinking in the very short-term mode about how they might translate that into gene therapy approaches to genetic diseases.
The expanded use of cell-based therapies — whether they are stem cells or other cells — is also having an impact. If we think about immunotherapy for cancer, we’re using either molecules or modified T-cells. We’re seeing cell-based therapies of all sorts coming forward.
We’re seeing expanded use of bone marrow transplantation for a wider range of autoimmune diseases.The trials that Dr. Harry Atkins (University of Ottawa) and others are doing on MS — those kinds of approaches are going to get more and more refined as we go forward.
Cardiac care is another area where we’re seeing clinical trials with many kinds of cells and molecules to treat heart disease. I think we’re going to see small incremental advances. A big advance has to come if we can actually fix the heart muscle. I know Dr. Gordon Keller (University of Toronto) and his colleagues are pushing very hard in that direction to try to move from cells in culture to bioengineered matrices of cells that you could think about using to replace damaged parts of the heart. Also, Dr. Michael Fehlings (University of Toronto) is very active in looking at a number of sources of cells that might be able to remyelenate axons in spinal cord repair.
These are all areas to watch in the future — the whole field is moving rapidly forward.
P.K Subban has done it. So has Mike Holmes. And Toronto’s infamous Mayor Rob Ford. Have you poured a bucket of ice water over your head to raise awareness — and funds — about ALS?…
P.K Subban has done it. So has Mike Holmes. And Toronto’s infamous Mayor Rob Ford. Have you poured a bucket of ice water over your head to raise awareness — and funds — about ALS? (more…)
News this week that Japanese and American scientists have found a third way to make pluripotent stem cells — a process that’s far simpler, faster and cheaper — is being heralded by some as a game-changing development in regenerative medicine.…
News this week that Japanese and American scientists have found a third way to make pluripotent stem cells — a process that’s far simpler, faster and cheaper — is being heralded by some as a game-changing development in regenerative medicine. Others say it may just be “a lab curiosity.”
Until now, there have been two main ways to create stem cells that are pluripotent (capable of producing any cell the body needs):
• harvesting them from embryos (embryonic stem cells), or
• reprogramming adult cells to function like embryonic stem cells (induced pluripotent stem cells).
Making embryonic stem cells has not been without controversy. And because creating induced pluripotent stem cells initially involved genetically altering things, there were concerns they could potentially cause tumours. While that problem apparently has been solved, the procedure is still a complex and costly one.
Now there is a third way — although, so far, it has only been done in animals. Researchers at the RIKEN Center for Developmental Biology in Japan and Brigham and Women’s Hospital and Harvard Medical School in the United States transformed blood cells from newborn mice into pluripotent cells called STAP cells. The technique involves stressing the cells by exposing them to trauma, low oxygen levels or mildly acidic solutions. Within days, the cells revert to an embryonic-stem-cell-like state. (A Boston Globe graphic illustrates the process beautifully. See it here.)
“It’s very simple to do,” Dr. Charles Vacanti of Brigham and Women’s Hospital in Boston, told the Associated Press after the two papers were published online Wednesday in Nature. “I think you could do this actually in a college lab.” Dr. Haruko Obokata of the RIKEN Center, said researchers are already at work to see if the technique can be replicated with human cells.
So, what to make of these new stem cells?
Dr. Chris Mason, chair of regenerative medicine bioprocessing at University College London, told Reuters that the approach was “the most simple, lowest-cost and quickest method” to generate pluripotent cells from mature cells. “If it works in man, this could be the game-changer that ultimately makes a wide range of cell therapies available using the patient’s own cells as starting material – the age of personalized medicine would have finally arrived.”
Others are more guarded. “Until you show it works in humans, it’s hard to know what the application is going to be,” the University of California’s Dr. William Lowry told AP. “For now, the question of whether it’s a lab curiosity or a big medical benefit; that’s still up in the air.”
To make sense of STAP, NewsDesk asked Dr. Janet Rossant (pictured above), Chief of Research and Senior Scientist at The Hospital for Sick Children for her assessment of this remarkable development.
“I don’t think it’s a game-changer,” says Dr. Rossant, President of the International Society for Stem Cell Research and one of the world’s leading embryonic stem cells scientists. “A game-changer means we’re all going to suddenly stop what we’re doing and do something else. It’s a surprising and intriguing observation, suggesting that somehow there is an intrinsic pluripotency program that is sitting there, waiting to be revealed if we stress the cells.”
She describes this as “one of those findings where you go, ‘Hmmm, that’s interesting.’ Of course, this is all mouse, so there is a need for further replication by other groups and further explanation of what the mechanism is. And, of course, extension to the human situation if this is going to have practical relevance. As it stands, I don’t see people are suddenly going to stop making induced pluripotent stem cells by the standard route. Because these cells, whatever they are, are not exactly identical to embryonic stem cells.”
The really important thing, according to Dr. Rossant, is that this discovery shows there “are multiple states of pluripotency out there” to be investigated. “We need to understand more about what we mean by the pluripotent state and whether it is a state that (cells) can fall back into.”
The true test of induced pluripotent stem cells, which were discovered in 2006 and earned Japan’s Dr. Shinya Yamanaka a Nobel Prize, was the fact other labs around the world could replicate the results. That will now be the challenge for STAP cells.
“It was a very surprising, intriguing result. It’s come from a reputable laboratory — RIKEN is one of the top developmental biology groups in the world,” says Dr. Rossant, who is a member of the Canadian Stem Cell Foundation’s Science Leadership Council.
“The question will be, ‘Is this a truly robust way of generating pluripotent stem cells?’ And only time will tell.”
Japan is moving forward with its plans to fast-track the use of induced pluripotent stem (iPS) cells to treat diseases — and revitalize its economy.…
Japan is moving forward with its plans to fast-track the use of induced pluripotent stem (iPS) cells to treat diseases — and revitalize its economy.
According to the Japan Times, the country last week officially passed a law “to promote safe and swift treatment using induced pluripotent stem (iPS) cells and other stem cells.” The legislation had previously received lower-house parliamentary approval.
As touched upon in an earlier post, Japanese scientists are now conducting world’s first human tests using iPS cells to treat age-related macular degeneration – the leading cause of vision loss in people over 50.
It’s no surprise they are first. Japan’s Dr. Shinya Yamanaka demonstrated how to create human iPs cells six years ago, inducing adult skin cells to become pluripotent (capable of differentiating into any cell the body needs). These cells function much like human embryonic stem cells but come without any controversy over destroying embryos to create them. The downside to iPS cells is a safety concern that the reprogrammed cells could potentially cause tumours to form. Researchers in Canada and around the world have been working on solutions to that.
Dr. Yamanaka won the 2012 Nobel Prize in Physiology or Medicine for his efforts. Throwing their support behind his work, Japan’s government recently announced it would invest more than $1 billion over the next 10 years in researching and developing iPS cells.
There is much more than national pride at stake, however. According to Bloomberg News, Prime Minister Shinzo Abe sees cellular regeneration as a key element of economic regeneration. His government, the report says, “estimates that stem cells’ potential to rejuvenate worn-out body parts or reverse degenerative diseases such as Alzheimer’s may yield $380 billion in sales by 2050.”
The macular degeneration trial involves just six patients using iPS cells generated from their own skin. It is a tiny study by any measure. But it represents a big step in the country’s efforts to develop a stake in that potential mega-billion-dollar market.