Stem Cells

02
Dec 2015
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Dr. Sheila Singh

Solving the Christopher mystery

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Dr. Sheila Singh is driven to know why one Christopher died when the other thrived.

About 20 years ago, while in her third year of a residency rotation and working in pediatric neurosurgery at Toronto’s SickKids Hospital, Dr.…

Dr. Sheila Singh is driven to know why one Christopher died when the other thrived.

About 20 years ago, while in her third year of a residency rotation and working in pediatric neurosurgery at Toronto’s SickKids Hospital, Dr. Singh was assigned two five-year-old boys. Both were named Christopher. Both had medulloblastoma, the most common kind of childhood brain tumour.

“I took care of them hour to hour, day to day. They both got the same surgery, the same chemo, the same radiation. In all clinical ways, the tumours were identical.  One Christopher did very well and was cured. The other died. I had this huge epiphany in that moment:  I realized that even if I did neurosurgery for the rest of my life, I would never figure out why one Christopher survived and one died.”

Dr. Singh realized that, along with being a brain surgeon, she needed to understand the molecular and cellular biology of brain tumours.  She entered the Surgeon Scientist Program at the University of Toronto where, while still a PhD student working in Dr. Peter Dirks’ lab, she was lead author on the 2004 Nature paper that identified human brain tumour initiating cells.

Since returning to her native Hamilton in 2007, Dr. Singh has worked as a pediatric neurosurgeon at McMaster Children’s Hospital while doing complementary research with Mac’s Stem Cell and Cancer Research Institute.

“There’s a bridge that connects the Children’s Hospital on the fourth floor to where my lab is and I go back and forth.  When I have a whole week of clinical work, where I’m covering emergency operations on call and doing clinics, you see everything that the children go through.  When I go back to the lab, I’m filled with clinical questions: Why did this happen to this child? It’s gratifying to have this research lab where I can bring questions to a useful end.”

In her research, Dr. Singh uses preclinical mouse models of brain cancer to improve treatments for her patients.

“We’ve developed ways of adapting the therapies that we use on children for immune-deficient mice. We transplant the human tumours into the mice and treat them with the exact same chemotherapy or radiation protocols that the children get. So I can profile — in a personalized medicine way — what’s going on with each child’s tumour. That’s the aim of these preclinical models: to model what’s going on in the patient in a faster, higher-throughput way. I’m hoping that one day we will have a model that will allow us to feed back to the patient:  ‘You have this cell population that’s going to escape radiation, so you are going to need this added drug to help you with your therapy.’”

Another approach is to take a sample of the child’s tumour cells and test the use of various compounds to defeat them. “We have a compound screening and drug screening program at the Institute.  So we can take the patient’s cells and screen them against libraries of thousands and thousands of compounds. Theoretically, we can find something that will work better as a therapy.”

Regardless of the approach, hers is the opposite of ivory tower, research-for-research-sake activity.  It is all patient-driven.

“You see a lot of things in pediatric neurosurgery and all of them — good and bad — inspire my research.  And every person who works with me has a direct connection to the ‘Why?’ of research.  Very often patients and their families will come for a tour of the lab and my people get to meet them.  There is a real connection. People in my lab work twice as hard because they have that direct motivation.”

On a personal level, doing research has made her a more patient person.

“Surgeons — we’re activists. We like to say, ‘OK, we’ll take that tumour out and you’ll feel better.’ But research requires long-term thinking.  Research forces me to be patient, have vision and plan in the long term. I’m not a patient person, but I’m learning.”

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04
Nov 2015
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cellCAN official

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Montreal event aims to separate stem cell myths from realities

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When it comes to stem cells and regenerative medicine, how can you tell the difference between fiction and reality?

Remarkable advances in stem cell research have led to sensational claims — especially from private clinics offering miraculous cures for a myriad of diseases. …

When it comes to stem cells and regenerative medicine, how can you tell the difference between fiction and reality?

Remarkable advances in stem cell research have led to sensational claims — especially from private clinics offering miraculous cures for a myriad of diseases.  But what’s the real story?

Our colleagues at CellCAN Regenerative Medicine and Cell Therapy Network hope to clear the air this week with an Information Day on Cell Therapy. The Thursday, Nov. 5th session at Montreal’s La Grande Place, complexe Desjardins – 150, Ste-Catherine West, runs from 10 a.m. to 4 p.m. with a panel discussion at noon.

CellCAN has developed an app for event participants to view to our Foundation’s Toward Treatments summaries of the state of stem cell research into 19 diseases.  You can find them here.

Organizers say the goal of the day is to distinguish “myths from the realities, and embrace the true potential of stem cells” so that “more Canadians benefit from this revolutionary medicine.”

 

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01
Oct 2015
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George Canyon, left, and David Prowten with Encaptra device

Canada AM highlights ‘closest thing to diabetes cure’

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This morning on Canada AM, country music star George Canyon and David Prowten, president of Juvenile Diabetes Research Foundation (JDRF) talked about their great hopes for a new stem cell device that could free diabetics from daily insulin injections. 

This morning on Canada AM, country music star George Canyon and David Prowten, president of Juvenile Diabetes Research Foundation (JDRF) talked about their great hopes for a new stem cell device that could free diabetics from daily insulin injections. 

Mr. Canyon, who has had type 1 diabetes since age 14, called the  device “the closest thing to a cure that I have ever seen … This is going to change the lives of 300,000 type 1 diabetics in Canada.”

Mr. Prowten, holding up the four-centimetre-long device, described it as “a big step forward.”

The Encaptra device, developed by a California-based biotechnology company called ViaCyte Inc. with help from the University of Alberta’s Dr. James Shapiro, has been featured in this space before.

Dr. Shapiro received Health Canada’s approval earlier this year to conduct a Phase1/2 clinical trial of the  stem cell-derived islet replacement treatment for diabetes.  It involves inserting the device, which is loaded with pancreatic progenitor cells, under the patient’s skin where new blood vessels grow around it and the body’s immune system doesn’t try to destroy it, enabling regulation of blood glucose levels. The Edmonton-based trial, supported by Alberta Innovates – Health Solutions and JDRF, follows one ViaCyte began last year in San Diego.

According to the Canada AM report, the first patient has now received the device. The early stage testing will be to see if the device is safe and is well tolerated. Within a year to 18 months scientists should learn if it actually works.  If it does,

“This could give me 10 to 12 months at a time of not really having diabetes, being able to go a day without testing, and taking insulin, Mr. Canyon said. “This is Disney World, right here.”

The report shows how close Canadian stem cell researchers are to delivering bold new therapies for a number of life-threatening conditions including, heart disease, cancer and Multiple Sclerosis. And it provides one more reason for telling politicians who are currently seeking your vote that you support the Canadian Stem Cell Strategy & Action Plan to bring more clinical trials to Canada. Take a minute to show your support here.

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15
Sep 2015
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Take the 2-minute test for Type 2 diabetes

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Are you at risk of having pre-diabetes or Type 2 diabetes?

According to the Canadian Diabetes Association (CDA), Type 2 diabetes occurs when the body can’t properly process insulin (called insulin insensitivity) or does not make enough insulin so that sugar builds up in the blood instead of being used as energy.…

Are you at risk of having pre-diabetes or Type 2 diabetes?

According to the Canadian Diabetes Association (CDA), Type 2 diabetes occurs when the body can’t properly process insulin (called insulin insensitivity) or does not make enough insulin so that sugar builds up in the blood instead of being used as energy. About 90% of people with diabetes have Type 2. It is more typical in adults, but children can be affected too.

The CDA has developed an online quiz for Canadians to see if they are at risk. Currently more than 9 million people in this country either have the disease or are in pre-diabetes. You can find out in just two minutes.  Click here to take the test.

Canada is a global leader in diabetes research. Almost 100 years ago, Frederick Banting and Charles Best discovered insulin and gave diabetics around the world the chance to live full lives. Now, Canadian stem cell researchers are working on ways to make those daily insulin injections a thing of the past via stem cell transplants.  The Canadian Stem Cell Strategy & Action Plan will help make it happen.  Click here to tell your federal candidates that you support the Action Plan — and that they should, too.

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27
Aug 2015
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Dr. Bernard Thébaud

Neonatal expert believes stem cells will revolutionize medicine

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 Dr. Bernard Thébaud believes that stem cells can help the tiniest of babies breathe easier. And now he has a grant to help make that happen.…

 Dr. Bernard Thébaud believes that stem cells can help the tiniest of babies breathe easier. And now he has a grant to help make that happen.

As Ottawa South News reported this month, Dr. Thébaud’s team is among 22 at the Ottawa Hospital awarded more than $28 million through a new grant offered by the Canadian Institutes of Health Research, the federal government’s health research funding agency. His team received $3.2 million.

“It’s a unique opportunity because instead of classical funding for three to five years for one project, it’s three projects for seven years,” Thébaud told the publication. “It gives you the peace of mind to work and get the job done.”

Dr. Thébaud’s six full-time researchers are working to translate stem-cell research into clinical treatments that can save lives. They have published papers showing that mesenchymal stem cells from umbilical cords could be used to treat bronchopulmonary dysplasia, or BPD, a disease that affects about 10,000 premature babies in North America every year.  These newborns receive oxygen via machines to help them survive. However this also damages their lungs and impedes development.

“We are one of the very few labs in the world that is banking on the therapeutic potential of these stem cells that may likely revolutionize medicine,” he told the publication.

Within 18 months, Dr. Thébaud plans to conduct a pilot study with up to 20 newborns to show that the stem cell therapy is feasible. If the results are positive, he will launch a randomized control trial, leading to the development of a new treatment.

His team is also investigating the use of another type of cord-blood stem cells, endothelial progenitor cells, to stimulate blood vessel growth and overall lung growth.

“It’s not about doing the science for the science’s sake,” he told the Ottawa South News. “It’s about driving the science and medication into the clinic.”

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17
Aug 2015
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Jeff Biernaskie Screen Captuer

Jeff Biernaskie

Researchers ask burn survivors: ‘What would make life better?’

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When Dr. Jeff Biernaskie and his University of Calgary Skin Regeneration Team set to work to build better skin grafts with stem cells, they wanted to talk to those with the most at stake: burn injury survivors.…

When Dr. Jeff Biernaskie and his University of Calgary Skin Regeneration Team set to work to build better skin grafts with stem cells, they wanted to talk to those with the most at stake: burn injury survivors.

“I came into this without the experience of working with patients,” says Dr. Biernaskie, an assistant professor in stem cell biology. “So I got together with a burn physician Dr. Vincent Gabriel, to ask, ‘What are the deficiencies somebody faces when they’ve had a burn and a skin graft?’ We wanted to ask them, ’What would make your quality of life better?’”

The team is conducting patient surveys to find out how burn survivors feel about their grafts, what their expectations are and how their priorities change over time.  They are also asking how burn survivors feel about stem cell transplants to regenerate dermal tissue — the thick layer under the epidermis that contains blood capillaries, nerve endings, sweat glands and hair follicles.

“It’s a different kind of pain in the beginning than it is later — often chronic itch is more problematic than pain in the long term” says Dr. Biernaskie. “A year later, you also may have limitations on mobility because of scarring.  So you may have a very different perspective on what you’d be willing to accept in terms of the risks — for example, the risk of aberrant growth, which might require additional surgeries — or the potential of failure of the stem cell transplant.

“These are real concerns, but by talking to patients living with skin grafts, our goal is to identify their most critical deficiencies and then design therapies to address those, so that any potential shortcomings are outweighed by the potential gains in function.”

The survey findings will help guide the Skin Regeneration Team as they move closer to conducting clinical trials on human patients. Right now, they are transplanting human dermal stem cells into skin-grafted mice, and seeing positive results.

“We’re seeing the cells respond in the appropriate ways, spreading out across the area of the graft.  What’s impressive to me is to see that the cells actually move up into the skin graft and interact with the epidermal cells, repopulating parts of the graft that may have been deficient. By regenerating new dermis, we hope that we can positively affect the function of the overlying epidermis, which otherwise is typically quite fragile after split thickness skin grafting. The cells are starting to secrete a lot of the collagens and the other factors needed to remodel that skin.”

They hope to be testing the stem cell transplants in larger animals such as pigs, which have skin more similar to that of humans, within two years.

“We want to look at the innervation (interaction with the nerves) of the graft, vascularity of the graft, as well as the histological (anatomical) functions of the graft.  All these things need to be looked at to see how much of an impact we’re having.”

Ultimately, the goal is to use the burn patient’s own skin cells to create millions of dermal stem cells that can be used for transplant, an autologous procedure that limits the risk of rejection and the need for immunosuppression drugs.

The team has cell biologists working on characterization of adult dermal stem cells — drawing them out of skin from an adult human and understanding the biology behind them.  They are also working with bioengineers to explore how to expand the cells using bioreactors to rapidly generate the large numbers of cells needed.

“We want to develop an autologous cell-based therapy to regenerate the dermis — that’s really our goal,” says Dr. Biernaskie. “I’m optimistic.  We can readily get the cells out from a patient, we’re able to grow them up from relatively small numbers of starting cells and we’re working on different matrices and scaffolds to improve survival and integration once they’re grafted in.”

He is even more optimistic about using stem cells to treat chronic skin wounds.

“Think of elderly patients with chronic wounds who are having their dressing changed every three days or so. That’s a lot of nursing costs, and bandages.  And it’s grueling for the patients. If you could take a biopsy, grow up a few hundred millions of cells, and then repopulate a chronic wound in order to get it to close and re-epithelialize, that would really have an impact on quality of life — and on the associated health care costs. That’s something we’re going to look at.”

The work being done by the Skin Regeneration Team is supported by Alberta Innovates Health Solutions and the Calgary Firefighters Burn Treatment Society.

Current care for burn injuries:
The current standard care for deep burns is split thickness skin grafting, which involves taking epidermis (outer) and part of the dermis (inner) layers of skin from elsewhere on the patient’s body and then grafting it onto the burn site.  Short term, the process is painful. Long term, additional grafts are often needed and the transplanted skin tends to scar, which can severely limit mobility, and are extremely fragile, leading to frequent wounds.  Also, the grafted skin is devoid of dermal appendages, such as sweat glands and hair follicles.

The potential stem cell solution:
Researchers hope stem cells drawn from the patient’s healthy skin can be coaxed to create millions of precursor cells than can be seeded into the dermal layer of the burn wound to generate new skin tissue that will fully integrate with the epidermal layer and help to grow new dermal appendages. The hope is that this regenerated tissue will be less prone to scarring and bleeding and provide better overall function.

[Find out more about stem cells and wound healing here.]

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13
Aug 2015
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Dr. Ivar Mendez

A stem cell solution to Parkinson’s?

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Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  …

Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  Walking becomes a stiff-limbed shuffle.

While drugs such as levodopa and dopamine agonists have greatly enhanced quality of life for Parkinson’s patients, their effectiveness diminishes over time. Deep brain stimulation has also proved helpful, but it does not slow the pace of neurodegeneration.

Stem cell transplants, however, may offer a longer-lasting solution.

“I think Parkinson’s is going to be the first neurological condition where stem cell therapy will be used widely,” says Dr. Ivar Mendez, Unified Head of the Department of Surgery at the University of Saskatchewan.  “We’re looking at transplanting one cell type. So we can direct the stem cells to become that type of cell — a Group A9 dopaminergic neuron.”

Transplanting cells into the brains of Parkinson’s patients in the hope of restoring dopamine neurotransmission is nothing new: it’s been going on for more than 25 years.  The results, according to a 2013 report in The Lancet, “have been variable and, thus, the merits of this approach have been both questioned and championed.”

The variation in results has been attributed to, among other things, the use of different strategies or protocols for transplanting the cells.  A key Canadian contribution to solving that problem is the Halifax Protocol for injecting cells into the human brain. Developed by Dr. Mendez, who was then at Dalhousie University, in collaboration with researchers from Toronto, Montreal and Calgary, the Halifax Protocol is regarded as the gold standard for effective brain repair using cell implantation.

“We developed the methodology for clinical transplantation,” says Dr. Mendez.  “When reviewers looked at all the grafts of all the patients who have been transplanted across the world, it was felt that ours did the best, in large part because of the methodology we developed.”

Dr. Mendez is working with fellow Parkinson’s stem cell pioneer Dr. Ole Isacson of Harvard to use induced pluripotent stem cells created from skin tissue to make dopamine-generating cells that, once transplanted, will integrate into the brain circuitry and restore motor function.

The process is autologous, meaning the stem cells come from the patient themselves, so no immunosuppression therapy is required. As well, researchers have come up with ways to generate the millions of cells required and have developed processes to make those cells robust enough to do the job.  So far, tests with large animals have shown positive results.

“We are continuing to work with animal models until we’re ready to start on a clinical trial, which should go ahead probably in the next two to three years,” says Dr. Mendez. “But I’m always concerned not to build unnecessary expectations among people affected by the disease.”

Other research centres are also working on a stem cell solution to Parkinson’s, with clinical trials using fetal cells currently underway in the United Kingdom.

“We’re very enthusiastic,” says Dr. Mendez. “Resolving the issue on a long-term basis, that is really the attraction. If one cell deteriorates or degenerates with time, can we actually replace that cell and reconstruct the circuitry? If we can, it’s a one-shot procedure. You do it only once and then the transplant will integrate into the host.”

Such a solution, however, could still be many years away.  Researchers need to be sure the cells they inject will do the intended job, without causing additional problems or perhaps generating tumours.

“We’re quite advanced in terms of realistically looking at a clinical trial,” says Dr. Mendez. “But we have to make sure that the preclinical scientific evidence is solid to ensure success”

[Find out more about stem cells and Parkinson’s here.] 

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10
Aug 2015
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Dr. Andy Becker

Andy Becker: stem cell pioneer and ‘amazing’ researcher

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Dr. Andy Becker, one of the true pioneers of stem cell science, has died in Toronto at age 80.

Dr.…

Dr. Andy Becker, one of the true pioneers of stem cell science, has died in Toronto at age 80.

Dr. Becker was the lead author of the 1963 paper, published in Nature, that definitively demonstrated the existence of stem cells. Using chromosomal markers, he retraced their steps after they had generated the three types of precursor cells needed to make blood.

“It was a key contribution to our early experimental investigations of stem cells,”Dr. Jim Till, who was Dr. Becker’s PhD  advisor at the time, wrote via email. “His combination of talent and persistence was what was needed to complete this challenging and innovative research. I’m still amazed at what he accomplished. I doubt if anyone else, at that time, could have succeeded in the way that Andy did.”

Dr. Becker worked closely with Drs. Ernest McCulloch and Till who, in 1961, had successfully shown that single cells drawn from bone marrow could produce colony-forming units containing the precursor cells required to make white blood cells, red blood cells and platelets. That paper laid the foundation for stem cell science.

A third Till & McCulloch paper — also published in 1963 but with Dr. Lou Siminovitch as lead author –proved that stem cells not only differentiate into new cells but also have the capacity to self-renew in order to keep the process going throughout our lifetimes. Combined, the three papers essentially defined stem cells and set the stage for regenerative medicine.

Dr. Becker’s paper proved just how tenacious a researcher he  could be. The chromosomal marker method was nothing if not painstakingly frustrating, given the rudimentary technology available at the time. In the University of Toronto Press book Dreams & Due Diligence, Dr. Becker’s wife, Prof. Clelia Ganoza, explains that he had a “killer instinct” for research, which meant that “the goal is the important issue and the obstacles to overcome are just needed lessons towards this end.”

As the Toronto Star obituary explains, Dr. Becker, who was also a medical doctor, not only did seminal work with stem cells but contributed greatly to the development of recombinant DNA technology.

Here at the Canadian Stem Cell Foundation, our hearts go out to Dr. Becker’s family, especially Prof. Ganoza, his wife of 47 years.

 

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26
Jun 2015
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Colon cancer: stem cells could lead to new target for treatment

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Canadian researchers have identified a new stem cell population in the colon linked to tumor growth. Their findings, published in Cell Stem Cell, could lead to new treatment approaches.…

Canadian researchers have identified a new stem cell population in the colon linked to tumor growth. Their findings, published in Cell Stem Cell, could lead to new treatment approaches.

Colorectal cancer is the third most common cancer and the second most common cause of death in Canada. On average, 423 Canadians are diagnosed with this type of cancer every week.

There are two kinds of stem cells in the intestine: a rapidly recycling one called Lgr5+ and a second slower one. Researchers at the Lawson Health Research Institute in London, Ontario have identified the second stem cell in the colon, one that is long-lived and radiation resistant. They also found that this new stem cell population not only gives rise to tumors in the colon, but also helps sustain and support the growth of the cancer.

According to Dr. Samuel Asfaha, a clinician-scientist at Lawson Institute and an assistant professor of medicine at the Schulich School of Medicine & Dentistry at Western University, the identification of the cellular origin of colorectal cancer is critical to understanding how cancer arises and identifying new targets for treatments.

“These findings are exciting as we have identified an important new target for cancer therapy. It is also proof that more than one stem cell can give rise to and sustain tumors, telling us that our cancer therapy needs to target more than one stem cell pool.” said Dr. Asfaha in a press release.

Until now, physicians believed that radiation therapy was effective. “With this new information, we now know this is not always true and we must find new forms of therapy to target the disease,” said Dr. Asfaha.

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28
May 2015
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Hitting a nerve: researchers turn blood into neural cells

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Stem cell researchers from McMaster University have found a way to turn human blood cells into neural cells, opening the door to new approaches to understanding and treating pain.…

Stem cell researchers from McMaster University have found a way to turn human blood cells into neural cells, opening the door to new approaches to understanding and treating pain.

The patented technique, described in a paper published in Cell Reports, involves extracting stem cells from blood and converting them into neural cells — like those found in the brain and the nervous system — over about a month.

“No one has ever done this with adult blood, to make this repertoire of neural cells, “Dr. Mick Bhatia, Director of McMaster University’s Stem Cell and Cancer Research Institute, told CTV News.

Dr. Bhatia and his team started working on the project after successfully converting skin cells into blood a few years ago. The researchers thought it would be useful to be able to make other kinds of cells from blood because it is easily accessible, regenerates on its own, and the resulting cells can be personalized.

“And so with this technology, blood could become a building block for neural cells,” Dr. Bhatia explained in CTV’s report.

The findings could lead to treatment advances for those suffering with chronic pain or nerve diseases. The researchers are  hopeful that one day it will be possible to take a blood sample from a patient and quickly produce a million nerve cells. They could then study those cells to better understand why certain people feel pain or why others experience numbness.

New pain medications that would specifically target neural cells, rather than just block the perception of pain, might also be developed thanks to the novel technique.”Pain is really poorly understood right now, and the drugs available are not well characterized,” Dr. Bhatia said in the CTV news report. “Most are narcotics and opioids that are addictive and they’re not very specific to the cells you’re trying to target.”

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