A new animal study using human cells shows that these new adaptive stem cells can remain dormant until needed.
A new study led by the University of New South Wales in Sydney shows that a new type of stem cell – that is, a cell with regenerative capabilities – could be closer on the horizon.
Stem cells (called induced pluripotent stem cells, or iMS) can be made from easily accessible human cells – in this case, lipids – and reprogrammed to function as stem cells.
The results of the animal study, which created human stem cells and tested their efficacy in mice, have been published online at Science advances Today – and while the results are encouraging, more research and testing is needed before any potential translation of human treatments.
“The stem cells that we developed can adapt to their surroundings and repair a host of damaged tissues,” says hematologist John Bimanda, professor at the University of New South Wales of Medicine and Health and co-author of the study.
To my knowledge, no one has ever made a human pluripotent adaptive stem cell. This is uncharted territory. “
Scientists created iMS cells in the laboratory by exposing human fat cells to a mixture of a compound that caused the cells to lose their original identity. This process also erased “gagging marks” – the markers responsible for restricting cell identity.
Researchers injected human iMS cells into mice where they initially remained dormant. But when mice suffered an injury, the stem cells adapted to their surroundings and turned into tissues that needed repair, be it muscle, bone, cartilage, or blood vessels.
“The stem cells behaved like a chameleon,” says lead author Dr. Avani Yola, a postdoctoral stem cell researcher in Professor Bemanda’s lab. Dr Yola conducted this work as part of her PhD thesis in Medicine and Health at the University of New South Wales.
“They have followed local signals to integrate into tissues that require healing.”
Current technologies for converting cells into stem cells do exist, but they have major limitations: Tissue-specific stem cells are inherently limited in the range of tissues they can create, and pluripotent stem cells (iPS) cannot be injected directly because they carry the risk of developing tumors. IPS cells also need additional treatment to create specific cell or tissue types before use. Further studies are needed to test how both stem cells and tissues created by tissue-specific stem cells function in humans.
The iMS cells, made from adult tissue, showed no sign of any unwanted tissue growth. It also adapted a range of different tissue types in mice.
“These stem cells are different from any other cells currently being evaluated in clinical trials,” says Dr. Yola.
“They are made from the patient’s cells, which reduces the risk of rejection.”
The study is based on the team’s 2016 study using mouse cells and is the next step before only human trials. But there is still a long wait – and more research to be done – to assess whether the cells are safe and successful in humans.
If iMS cells prove safe for human use, they could one day help repair anything from traumatic injuries to heart damage.
“This is another step forward in the field of stem cell therapy,” says Dr. Yola.
Simple yet powerful technology
Every human cell – be it a heart cell or a brain cell – shares the same DNA content. Cells look and act differently because they use different parts of their DNA.
The parts of DNA that cells don’t use are usually closed by natural modifications.
“The idea behind our approach was to reverse these adjustments,” says Professor Bimanda.
“We wanted cells to have the option to use this piece of DNA if there was a signal from outside the cell.”
Researchers reprogrammed the fat cells with two compounds: azacitidine, a drug used to treat leukemia. It is a natural growth factor that stimulates cell growth and tissue repair.
The cells released their lipids and lost their identity as a fat cell after about three and a half weeks of treatment.
“This is a very simple technique,” says Dr. Vashi Chandrakanthan, a senior research fellow at the University of New South Wales of Medicine and Health and co-author of the study. Dr Chandrakanthan, who led the 2016 mouse study with Professor Bimanda, came up with the idea to create iMS cells.
He says there are two main possibilities for a potential clinical application.
One idea is to take a patient’s fat cells and place them in a machine where they are incubated with this compound. When ready, these reprogrammed cells can be placed in a vial and then injected into the patient, ”Dr. Chandrakanthan says.
“Another option is to combine the two compounds into a simple, small pump that can fit into the body, such as a pacemaker.”
Theoretically, this small pump could be placed near the part of the body that needs help (for example, the heart), where it could dispense regulated doses to create new stem cells.
I look forward
While the results are encouraging, the researchers recognize that a potential translation of human treatments remains elusive.
“Safety is our foremost concern,” says Professor Bimanda.
“Preclinical studies and clinical trials have yet to be done, and we need to make sure that we can produce these cells in a safe condition.”
“Industry partners can bring expertise in producing clinical-grade iMS cells and designing and conducting clinical trials,” he says. This will help move this research to the next stage.
Dr Chandrakanthan says that if future studies are successful, introducing this treatment in the real world could take up to 15 years.
Dr. There can be roadblocks, setbacks, and failed experiences. It is the nature of research.
“Although these results are very exciting, I will maintain my enthusiasm until we reach patients.”