Around the world, scientists are conducting clinical trials to transform stem cells––which make endless copies of themselves––into other types of cells, such as lung, brain, heart, or muscle cells, and use the new cells to cure ailments ranging from diabetes to heart disease, according to a presentation by Professor Janet Rossant at the Royal Society Commonwealth Science Conference in Singapore. Rossant is a pioneer in the field of stem-cell research.
While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. Scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.
“There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants,” Rossant said.
Now a senior scientist at the Hospital for Sick Children in Toronto, Canada, she was the first to demonstrate the potential of stem cells in mice.
In the early 1990s, scientists believed that stem cells could become only certain types of cells and carry out limited functions. Based on her research and that of others, however, Rossant believed that they were capable of much more.
Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. “We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish,” she said.
“That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body,” she added.
When scientists learned how to remove stem cells from human embryos in 1998, however, controversy followed. Many lobbied against the cells’ use in medical research and treatment because of the moral implications of destroying even unwanted embryos to gain the cells.
In Canada, Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field.
In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.
While stem cells have been used for medical treatment––bone marrow transplants, for example, are a form of stem cell therapy––several challenges need to be overcome before they can be used more widely to treat diseases and injuries.
“We need to get better at turning stem cells into the fully mature cells that you need for therapy. That’s going to take more work. Another issue is that of scale-up. If you’re going to treat a patient, you need to be able to grow millions of cells,” Rossant said.
She added: “Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that’s also one of the scariest things about them, because that’s also how cancer works.
“Furthermore, because we need to genetically manipulate cells to get IPS cells, it’s very hard to know whether we’ve got completely normal cells at the end of the day. These are all issues that need to be resolved.”
Rossant noted that some scientists are working on making “failsafe” IPS cells, which have a built-in self-destruct option if they become dangerous. “Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration,” she said.
In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and to test drugs. “That’s the biggest use of IPS cells right now,” Rossant said.
At the Hospital for Sick Children, she has been using stem cells to study cystic fibrosis (CF), a frequently fatal genetic disorder that causes mucus to build up and clog some organs, such as the lungs. It affects primarily children and young adults.
The Hospital for Sick Children discovered the CFTR gene that, when mutated, causes CF. It was also the first to produce mature lung cells from stem cells, which can be used to study CF and to test drugs against it.
Further, Rossant and her team were able to turn skin cells from CF patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalizing treatment for each patient.
“Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug,” Rossant explained. “With our work, we can make sure that each patient gets the right drug at the right time.”
In 1998, Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These cells surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placental defects and pregnancy problems.
By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs’ efficacy and identify potential adverse effects, as well as develop personalized medications.
“There are still huge amounts of opportunities in pluripotent stem cells,” Rossant said.
Source: ResearchSEA; June 22, 2017.