[University of New South Wales]
Scientists took one step closer to mimicking the biology of animals such as salamanders, which can regenerate entire limbs, through the creation of an induced multipotent stem (iMS) cell. It is conceivable that this new development could be used to repair everything from spinal discs to bone fractures and has the potential to transform current treatment approaches to regenerative medicine.
Researchers at the University of New South Wales (UNSW) demonstrated in mice that they could reprogram bone and fat cells into iMS cells. These findings were published recently in Proceedings of the National Academy of Science in an article entitled “PDGF-AB and 5-Azacytidine Induce Conversion of Somatic Cells into Tissue-Regenerative Multipotent Stem Cells.”
“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,” explained senior study author John Pimanda, M.D., Ph.D., associate professor at UNSW. “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 numerous types of stem cells, such as 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. Before the current study, there were no adult stem cells that could regenerate multiple tissue types.
“This technique is ground-breaking because iMS cells regenerate multiple tissue types,” Dr. Pimanda noted. “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 UNSW investigators developed the technique by 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 2 days. The cells are then treated with the growth factor alone for a further 2–3 weeks.
AZA has been shown previously to induce cell plasticity—a crucial step in 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. This method represents 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 tumor-forming capacity,” remarked lead study author Vashe Chandrakanthan, Ph.D., senior lecturer at UNSW. “The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable. We believe we've overcome these issues with this new technique.”
Ralph Mobbs, M.D., neurosurgeon and conjoint lecturer with UNSW's Prince of Wales Clinical School and co-author on the current study added that, “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.”
“Spinal implants currently used to replace damaged or troubled discs don't always weld with the adjacent bones,” continued Dr. Mobbs, who will lead the human trials once the safety and effectiveness of the technique have been demonstrated. “So, by transplanting these reprogrammed stem cells, we hope to be able to better fuse these implants to the host bone. This represents a potentially huge leap forward for spinal and orthopedic procedures.”
Along with confirming that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice, the researchers stated that further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand.