Not All Induced Pluripotent Stem Cells are Made Equal

Not All Induced Pluripotent Stem Cells are Made Equal

Wednesday, 03 December 2014

Mick Bhatia, Scientific Director, McMaster Stem

Cell and Cancer Research Institute, Canada

Research Chair in Human Stem Biology,

Professor, Department of Biochemistry and 
Biomedical Science, McMaster University.

Scientists at McMaster University have discovered that human stem cells made from adult donor cells "remember" where they came from and that's what they prefer to become again.

This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients.

Pluripotency is the ability stem cells have to turn into any one of the 226 cell types that make up the human body. The work challenges the previously accepted thought that any pluripotent human stem cell could be used to similarly generate the same amount of mature tissue cells.

This finding, published today in the prestigious science journal Nature Communications, will be used to further drug development at McMaster, and potentially improve transplants using human stem cell sources.

Human blood cells in a dish. Cells were

reprogrammed to stem cells from blood and were

10x more effective than using skin as a starting 
tissue. 

The study was led by Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell Biology and he is a professor in the Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine.

"It's like the stem cell we make wants to become a doctor like its grandpa or an artist like its great-grandma," said Bhatia.

"We've shown that human induced pluripotent stem cells, called iPSCs, have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states.”

"So, not all human iPSCs are made equal," Bhatia added.

"Moving forward, this means that iPSC generation from a specific tissue requiring regeneration is a better approach for future cellular therapies. Besides being faster and more cost-efficient in the development of stem cell therapy treatments, this provides a new opportunity for use of iPSCs in disease modelling and personalized drug discovery that was not appreciated before."

Neural cells generated from patient-specific stem 
cells. 

Small quantities of tissue would need to be harvested from the patient; for example, a few millilitres of blood or a small skin punch biopsy. From there, the harvested cells can be put into various stem cell states where they make copies of themselves indefinitely. The trickier part has been to get them out of copy function model and into differentiation mode to produce the cells needed for researchers to test drug therapies with no harm to patients, said Bhatia.

The McMaster Stem Cell and Cancer Research Institute is the only Canadian university team continuing to work exclusively with the more fragile human stem cells rather than mouse stem cells for its research, and that has furthered the work to future clinical impact. By contrast, the iPSCs of mice, which are widely used in stem cell research, have no memory, the authors note.

"So, if you only studied the mouse alone, you'd never uncover this opportunity," said Bhatia.

In a previous discovery, Bhatia and his team discovered how to make human blood from adult human skin. This meant that patients needing blood would be able to have blood created from a patch of their own skin to provide transfusions.

With these new findings, "our starting block has changed," said Bhatia, adding that now researchers "can make better tailored human stem cells for therapies because we've got a more efficient way of making higher quality and quantity of cells. For example, our team has shown that the stem cells that come from blood in the first place make blood 10 times better."

Source: McMaster University

Contact: Veronica McGuire

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Umbilical Cord Blood, at the Cutting Edge of Today’s Medicine

“Saving Grace”

From: Al Jazeera America’s TECHKNOW Presents

Thursday, 17 July 2014

This Saturday, July 19th at 7:30 pm ET/4:30 pm PT, Al Jazeera America’s “TechKnow” shows us one of the most exiting areas of medical research – how umbilical cord blood is being used to treat brain disease and injury.

Dr. Joanne Kurtzberg. Credit: Al Jazeera.

“Techknow” host and mechanical engineer Dr. Shini Somara takes us inside Duke Children’s Hospital, where a team of doctors is treating young Grace Matthews, an infant with hydrocephalus, or water on the brain, characterized by the tell-tale swelling of the baby’s head.  We go behind-the-scenes on the high-tech experimental treatments, as doctors infuse Grace with stem cells from her own umbilical cord, and we meet another young patient who experienced “miraculous” progress from the use of umbilical cord stem cells.

The medical equivalent of gold, we’re just at the tip of understanding how stem cells from cord blood, harvested at the time of birth, can be used to help the brain regenerate and heal from injuries and damage.

“I personally believe cell therapy, and regenerative medicine, is going to be the next big advance in medicine, and that cells like cord blood are going to drive that forward,” reports Dr. Joanne Kurtzberg, Chief of the Division of Pediatric Blood and Marrow Transplantation at Duke University Medical Center in Durham, North Carolina.

The program is airing Saturday, July 19th at 7:30PET/4:30P PT;

Repeats 10:30P ET/7:30P PT

Find Al Jazeera America near you: www.aljazeera.com/getajam

About Al Jazeera America’s “TechKnow”:

Al Jazeera America’s “TechKnow” is a half hour documentary show that airs weekly on Saturdays at 7:30 pm ET/4:30 pm PT.  A show about innovations that can change lives, “TechKnow” explores the intersection of hardware and humanity in a unique way – it’s a show about science, by scientists. “TechKnow” rotating cast of hosts includes mechanical engineer Dr. Shini Somara, molecular neuroscientist Dr. Crystal Dilworth, entolomologist Phil Torres, biologist Marita Davison, engineer Kosta Grammatis, science writer Kyle Hill, former CIA operative and analyst Lindsay Moran, neuroscientist Rachelle Oldmixon and neurobiologist Cara Santa Maria.

Source: Al Jazeera America’s “TechKnow”

Contact: Jocelyn Austin, Director, Publicity

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Stem Cells Enable Personalised Treatment for Bleeding Disorder

Stem Cells Enable Personalised Treatment for Bleeding Disorder

Friday, 05 April 2013

Scientists have shed light on a common bleeding disorder by growing and analysing stem cells from patients' blood to discover the cause of the disease in individual patients.

The technique may enable doctors to prescribe more effective treatments according to the defects identified in patients' cells.

In future, this approach could go much further: these same cells could be grown, manipulated, and applied as treatments for diseases of the heart, blood and circulation, including heart attacks and haemophilia.

The study focused on von Willebrand disease (vWD), which is estimated to affect 1 in 100 people and can cause excessive, sometimes life-threatening bleeding. vWD is caused by a deficiency of von Willebrand factor (vWF), a blood component involved in making blood clot. vWF is produced by endothelial cells, which line the inside of every blood vessel in our body. Unfortunately, they are difficult to study because taking biopsies from patients is invasive and unpleasant.

A group led by Dr Anna Randi at the National Heart and Lung Institute,Imperial College London used a new approach to investigate the disease. Dr Richard Starke, a British Heart Foundation Intermediate Fellow and lead author of the study, took routine blood samples from eight patients with vWD, extracted stem cells called endothelial progenitor cells, and grew them in the lab to yield large numbers of endothelial cells.

By testing these cells, they were able to analyse each patient's disease in unprecedented detail. In some patients, the scientists found new types of defect, which may enable them to recommend improved treatments. Professor Mike Laffan, a collaborator in the study and in charge of patients with VWD at Hammersmith Hospital in West London, is looking to apply these findings to reduce severe bleeding in these patients.

Dr Randi believes that endothelial progenitor cells could become an invaluable resource for testing new drugs for vWD and other diseases.

"We will be able to test the effects of a range of compounds in the patients' own cells, before giving the drugs to the patients themselves," she said.

This approach could have impact far beyond vWD. Endothelial cells derived from blood could also be isolated and reinjected into someone recovering from a heart attack, to help them grow new blood vessels and repair the injured heart tissue. Dr Starke says this approach avoids the main problem with transplant therapies, in which the immune system tries to destroy the foreign material.

"The patients would receive their own cells, so they wouldn't face the problems of rejection," he said.

Work is well underway towards achieving this goal, but blood-derived endothelial cells are only now being explored.

"There are already many studies where patients have been injected with stem cells to see whether damage to the heart could be repaired, and there are some promising results," says Dr Randi.

"The door is open to such treatments, and our studies are a step towards identifying the right cells to use."

The group's previous research has already thrown up pointers for potential new treatments. Aside from producing vWF to form clots, endothelial cells are responsible for forming new blood vessels. In their last paper, the group showed that vWF is actually needed to build healthy blood vessels. Some patients with vWD suffer severe bleeding from the gut because defects in vWF cause their blood vessels to develop abnormally.

"There are drugs already being used in other diseases which target abnormal blood vessel, that could be useful to stop bleeding in some vWD patients," says Randi.

"Nobody would have thought of using them to treat vWD, but by testing them on the patient's own endothelial cells, in the laboratory, we can find out if these drugs work before giving them to the patient."

Scientists are now interested in the possibility of using endothelial cells as a treatment in themselves. For instance, haemophilia, the hereditary bleeding disorder which affected Queen Victoria's family, might one day be treated by taking these cells from a patient and replacing the gene that causes the disease, then putting them back into the patient.

Funding for the study came from the British Heart Foundation, the Medical Research Council and the National Institute for Health Research, Imperial Biomedical Research Centre.

Source: Imperial College London 

Contact: Sam Wong

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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