Tailoring embryonic stem cells to treat eye disease

Researcher Fredrik Lanner hopes that learning more about how human embryo cells are formed may help us understand the causes of infertility. His research is also central to the development of stem cell therapies for age-related macular degeneration (AMD) – an eye disease that affects nearly one-fifth of all people over the age of 65.

Fredrik Lanner

PhD Developmental Biology

Wallenberg Academy Fellow 2016

Institution:
Karolinska Institutet

Research field:
Development of human embryonic stem cells in the early embryo

“I’m mainly driven by a desire to understand how human biology works. But of course it would be fantastic if I could play a part in discovering something capable of curing diseases,” Lanner says.

He leads the way to the research team’s laboratories. Novum Research Park is right next door to Karolinska University Hospital in Huddinge, south of Stockholm. Here, Lanner and his colleagues are conducting basic research into human embryonic stem cells, which form during the first few days after an egg has been fertilized.

Their research is possible thanks to the availability of donated embryos from couples at the IVF clinic in the same building. Embryos not used for infertility treatment should be destroyed, but may instead be donated for research. This is where Lanner’s work comes into the picture.

­ “We study how the human embryo develops at molecular level during the first week, which can teach us more about the causes of infertility. We also want to learn more about how embryonic stem cells are created and regulated in the embryo. As a third line of inquiry, we are using the cells to develop a stem cell therapy for a serious eye disease – age-related macular degeneration.”

A five-year grant from the Knut and Alice Wallenberg Foundation will give Lanner the freedom to continue his multi-pronged approach.

“The grant gives us the courage to pursue our “broadside” approach, with three lines of research that complement one another to form a whole. Without funding from the Foundation, I think I would have been forced to prioritize much more harshly.”

“It’s great to have three lines of research – and it’s exciting to move from basic research to treating patients. But it’s also an enormous challenge.”

Gene map

When Lanner began studying biology at Stockholm University he had a passion for diving, and was interested in marine biology. But then his eyes were opened to developmental biology. Since then he has focused on ways of using embryonic stem cells to understand how the body is formed.

As a postdoc at the Hospital for Sick Children in Toronto, Canada, he was involved in the discovery of some important pieces in the puzzle of how the first cell types are created, and differentiate in mice.

“But when we tried to transfer our knowledge to humans, it was obvious that the fundamental mechanisms governing the human embryo are not the same as those in mouse embryos. To truly understand human development, we have to look inside the human embryo.”

During the early stages that Lanner is studying, the embryo is made up of no more than 200 cells, compared with a new-born baby, which has several hundred billion cells.

“We’ve established which genes are active during the first few days after fertilization. Now we want to see what happens from the time when stem cells differentiate to form three specific cell types up to the point at which the embryo normally is implanted in the womb.”

Lanner explains that those three cell types have to mature – differentiate – in the right way so they can then develop into the placenta, fetal membrane, and embryo in the pregnant woman. The research team is examining the genes that regulate the cell maturation process. To do so, they are using a tool called CRISPR, which is usually referred to as a “gene snipping” tool.

“CRISPR is faster, simpler, and maybe a thousand times more efficient than earlier technologies. We have just started work on optimizing the methodology.”

Treating AMD

For some years now, Lanner has been collaborating closely with eye surgeon Anders Kvanta at St Erik Eye Hospital. They are developing stem-cell treatment for macular degeneration, which is an age-related change in the macula lutea, also known as the “yellow spot” or fovea. This common eye disease leads to permanently impaired vision as pigmented epithelial cells in the retina begin to die.

“There are two types of macular degeneration – a wet form and a dry form. The wet form is treatable, but not the dry form, which is more common,” Lanner explains.

A stem cell bank is being established in an ultraclean laboratory at Novum. The bank consists of high-quality human embryonic stem cells for use in transplants, or as a basis for drugs. Among other things, the team is manufacturing retinal pigmented epithelial cells that have differentiated from embryonic stem cells on a special substrate.

“We hope that if we can transplant these cells in the patient at an early stage, we will be able to halt the loss of vision.”

Research involving human embryos is sensitive, and requires a number of ethical approvals. The team conducts an ongoing dialogue on ethical issues in the lab. Lanner elaborates:

“My view is that if we can use surplus embryos from IVF treatment to generate more knowledge, we may be able to help more couples to have children, or produce stem cells that can be used for medical purposes. If so, then I think that the research is ethically defensible.”

Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström