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EXPERT REACTION: Australian scientists develop ‘game changing’ stem cell repair system

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Stem cell therapies capable of regenerating any human tissue damaged by injury, disease or ageing could be available within a few years, following landmark research led by UNSW Australia researchers. The repair system, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and has the potential to transform current treatment approaches to regenerative medicine.

Journal/conference: Proceedings of the National Academy of Sciences

Organisation/s: The University of New South Wales

Media Release

From: The University of New South Wales

Stem cell therapies capable of regenerating any human tissue damaged by injury, disease or ageing could be available within a few years, following landmark research led by UNSW Australia researchers.

The repair system, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and has the potential to transform current treatment approaches to regenerative medicine.

The UNSW-led research has been published today in the Proceedings of the National Academy of Sciences journal.

Study lead author, haematologist and UNSW Associate Professor John Pimanda, said the new technique, which reprograms bone and fat cells into induced multipotent stem cells (iMS), has been successfully demonstrated in mice.

“This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation,” Associate Professor Pimanda said.

“We are currently assessing whether adult human fat cells reprogrammed into iMS cells can safely repair damaged tissue in mice, with human trials expected to begin in late 2017.”

There are different types of stem cells including embryonic stem (ES) cells, which during embryonic development generate every type of cell in the human body, and adult stem cells, which are tissue-specific. There are no adult stem cells that regenerate multiple tissue types.

“This technique is ground-breaking because iMS cells regenerate multiple tissue types,” Associate Professor Pimanda said.

“We have taken bone and fat cells, switched off their memory and converted them into stem cells so they can repair different cell types once they are put back inside the body.”

The technique developed by UNSW researchers involves extracting adult human fat cells and treating them with the compound 5-Azacytidine (AZA), along with platelet-derived growth factor-AB (PDGF-AB) for approximately two days. The cells are then treated with the growth factor alone for a further two-three weeks.

AZA is known to induce cell plasticity, which is crucial for reprogramming cells. The AZA compound relaxes the hard-wiring of the cell, which is expanded by the growth factor, transforming the bone and fat cells into iMS cells. When the stem cells are inserted into the damaged tissue site, they multiply, promoting growth and healing.

The new technique is similar to salamander limb regeneration, which is also dependent on the plasticity of differentiated cells, which can repair multiple tissue types, depending on which body part needs replacing.

The study’s first author, Dr Vashe Chandrakanthan, who developed the technology, said the new technique is an advance on other stem cell therapies being investigated, which have a number of deficiencies.

“Embryonic stem cells cannot be used to treat damaged tissues because of their tumour forming capacity. The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable,” Dr Chandrakanthan said.

“We believe we’ve overcome these issues with this new technique.”

Neurosurgeon and Conjoint Lecturer with UNSW’s Prince of Wales Clinical School, Dr Ralph Mobbs, will lead the human trials, once the safety and effectiveness of the technique using human cells in mice has been demonstrated.

“The therapy has enormous potential for treating back and neck pain, spinal disc injury, joint and muscle degeneration and could also speed up recovery following complex surgeries where bones and joints need to integrate with the body,” Dr Mobbs said.

Research shows that up to 20% of spinal implants either don’t heal or there is delayed healing. The rates are higher for smokers, older people and patients with diseases such diabetes or kidney disease.

“Spinal implants currently used to replace damaged or troubled discs don’t always weld with the adjacent bones, so by transplanting these reprogrammed stem cells, we hope to be able to better fuse these implants to the host bone,” Dr Mobbs said.

“This represents a potential huge leap forward for spinal and orthopaedic procedures.”

Along with confirming that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice, the researchers said further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand.

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor Martin Pera is Program Leader of Stem Cells Australia and Chair of Stem Cell Sciences at the University of Melbourne, Florey Neuroscience and Mental Health Institute and the Walter and Eliza Hall Institute of Medical Research

This study used 5-azacytidine, a cancer chemotherapy drug discovered many years ago, to modify the properties of stem cells derived from bone marrow or fat.  The observations are interesting, but the study does not demonstrate that these cells have properties similar to pluripotent stem cells derived from embryos or through reprogramming.  It will be some time before the therapeutic implications of this work become clear

Last updated: 03 Nov 2016 4:49pm
Dr Bryce Vissel is a Professor in the School of Clinical Medicine at UNSW and Director of the Centre for Neuroscience and Regenerative Medicine at St Vincent's Hospital Sydney  

This excellent research led by John Pimanda is world leadership by Australian scientists. The study, published in the prestigious journal PNAS, provides  a viable method for generating regenerative stem cells for repairing tissue and bone damage.

Importantly, the method developed by Vashe Chandrakanthan and team under John Pimanda’s leadership appears safe and therefore has real implications for repairing tissue and bone damage in humans. The work demonstrates again that Australian research has potential to bring outcomes for Australian’s health and economy, both by reducing burden of disease and by generating Australian intellectual property.  The next experiment, testing whether these regenerative stem cells can help humans is an urgent next step that the researchers must and will pursue."
 
In more detail:

"There has been much controversy over the use of fat-derived stem mesenchymal stem cells for treating a range of problems, mainly because it is unclear as to whether fat-derived stem mesenchymal stem cells are truly effective. This new study led by John Pimanda provides a major advance over such methods. The research demonstrates that it is possible to take mouse or human cells such as fat cells (adipocytes) or bone cells (osteocytes) and convert them into genuine regenerative stem cells that can effectively repair damaged tissue. 
 
The method developed by the team is an important and exciting advance, because it relies only on the use of two widely available chemical agents that are simply applied to the fat cells or bone cells to convert them to the regenerative stem cells. This avoids more complex and potentially more dangerous methods currently used to generate regenerative stem cells, often called induced pluripotent stem cells.  The exciting next experiment showed that the mouse bone derived stem cells can be transplanted back into damaged spine tissue and repairs damage to the bone, muscle and ligaments and even blood vessels in the spine. Most critically, unlike other stem cells, the regenerative stem cells did not form tumours or unwanted cell types, meaning that they are likely to be safe for use in humans.  It is very important now that the experiment is taken forward to testing in humans to see if this is safe and effective for treating human tissue injury. 
 
This research by many outstanding Australian scientists working together in close collaboration is exemplary and the next steps of establishing safety and efficacy in humans eagerly awaited.

Last updated: 03 Nov 2016 3:55pm

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    Stem cell therapies capable of regenerating any human tissue damaged by injury, disease or ageing could be available within a few years, following landmark research led by UNSW Australia researchers.

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