Researchers at University of New South Wales are developing ‘smart’ stem cells from human fat. The new, adaptive stem cells can lie dormant until needed, a new animal study using human cells shows.
The results of the animal study, which created human stem cells and tested their effectiveness in mice, were published online in Science Advances. If shown to be safe for human use, the stem cells (called induced multipotent stem cells, or iMS) could one day help mend anything from traumatic injuries to heart damage.
“The stem cells we’ve developed can adapt to their surroundings and repair a range of damaged tissues,” says haematologist John Pimanda, a professor at UNSW Medicine and Health, and co-senior author of the study.
The stem cells acted like chameleons
“To my knowledge, no one has made an adaptive human multipotent stem cell before. This is uncharted territory.”
The scientists created the iMS cells in a lab by exposing human fat cells to a compound mixture that caused the cells to lose their original identity. This process also erased ‘silencing marks’ – marks responsible for restricting cell identity.
They then injected the human iMS cells into mice where they initially stayed dormant. However, when the mice had an injury, the stem cells adapted to their surroundings and transformed into the tissue that needed repairing, be it muscle, bone, cartilage, or blood vessels.
“The stem cells acted like chameleons,” said lead author Dr Avani Yeola, a post-doctoral stem cell researcher in Prof Pimanda’s laboratory. Dr Yeola conducted this work as part of her doctoral thesis at UNSW Medicine and Health.
“They followed local cues to blend into the tissue that required healing.”
There are existing technologies to transform cells into stem cells, but they have key limitations: tissue-specific stem cells are inherently limited in the range of tissues they can create, and induced pluripotent stem (iPS) cells cannot be directly injected because they carry a risk of developing tumours. iPS cells also need extra treatment to generate specific cell types or tissues before use. More studies are needed to test how both iPS cells and tissues created by tissue-specific stem cells function in humans.
iMS cells, which are made from adult tissue, showed no sign of any unwanted tissue growth. They also adapted to a range of different tissue types in mice.
“These stem cells are unlike any others currently under evaluation in clinical trials,” says Dr Yeola. “They are made from a patient’s own cells, which reduces the risk of rejection.”
The study builds on the team’s 2016 study using mouse cells and is the next step before human-only trials. But there is still a long wait – and much more research to be done – to assess whether the cells are safe and successful in humans.
TOOLS OF REPROGRAMMING
The researchers reprogramed fat cells using two compounds: azacitidine, a drug used in blood cancer therapy; and a naturally occurring growth factor that stimulates cell growth and tissue repair.
The cells released their fat and lost their identity as a fat cell around three and a half weeks after treatment.
“This is a very simple technology,” says Dr Vashe Chandrakanthan, a senior research fellow at UNSW Medicine and Health and co-senior author of the study. Dr Chandrakanthan, who led the 2016 mouse study with Prof Pimanda, came up with the idea of creating iMS cells.
He said there are two main possibilities for potential clinical application.
“One idea is to take the patient’s fat cells, and put them into a machine where it incubates with this compound. When ready, these reprogrammed cells could be put into a vial, and then injected into the patient,” says Dr Chandrakanthan.
“Another option is to combine the two compounds into a simple mini-pump that could be installed in the body, like a pacemaker.”
This mini-pump could theoretically be put near the body part needing assistance (for example, the heart), where it could dispense regulated doses to create new stem cells.
Preclinical and clinical studies need to be done and Dr Chandrakanthan said if successful, a real-world delivery of this therapy could take anywhere up to 15 years.
“Successful medical research that achieves its final goal – that is, translating to routine clinical applicants and treatment – can often take many decades. There can be barriers, setbacks and failed experiments. It’s the nature of research… I will keep a lid on my excitement until we get this through to patients.”