Australian researchers have demonstrated an exciting new way to regenerate human tissue with stem cells.

The repair system mimics the method used by salamanders to regenerate limbs.

The significant advance means stem cell therapies for regenerating any human tissue damaged by injury, disease or ageing could be available within a few years.

The new technique has been used to reprogram bone and fat cells into induced multipotent stem cells (iMS) 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, “ says lead author of the landmark study, UNSW haematologist Associate Professor John Pimanda.

“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 several kinds of stem cells, including early-life embryonic stem (ES) cells, which can turn into every type of cell in the human body.

However, as we age these are replaced by adult stem cells, which can only generate specific kinds of tissues.

The new approach creates iMS cells, which are important because they can regenerate multiple tissue types.

“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,” Associate Professor Pimanda said.

Researchers extracted adult human fat cells and treated 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 also depends on the plasticity of differentiated cells, which can repair multiple tissue types, depending on which body part needs replacing.

“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,” said the study’s first author, Dr Vashe Chandrakanthan.

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

The experts say the next step will be to confirm that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice.

Then, further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand.

The latest study is available here, and the University of New South Wales has posted a video explaining the technique here.[ https://youtu.be/zAMCBNujzzw]

Dr Bryce Vissel, the Roth Fellow Head of Neurodegeneration Diseases Research Laboratory at the Garvan Institute of Medical Research, reflects on the breakthrough below.

“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,” he said.

“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.”