Nav: Home

Advances in production of retinal cells for treating blindness

March 30, 2020

Researchers at Karolinska Institutet and St Erik Eye Hospital in Sweden have discovered a way to refine the production of retinal cells from embryonic stem cells for treating blindness in the elderly. Using the CRISPR/Cas9 gene editing, they have also managed to modify the cells so that they can hide from the immune system to prevent rejection. The studies are published in the scientific journals Nature Communications and Stem Cell Reports.

Age-related macular degeneration of the eye is the most common cause of blindness in the elderly. This loss of vision is caused by the death of the photoreceptors (the rods and cones) resulting from the degeneration and death of the underlying retinal pigment epithelial (RPE cells), which provide the rods and cones vital nourishment. A possible future treatment could be to transplant fresh RPE cells formed from embryonic stem cells.

Working with colleagues at St Erik Eye Hospital, researchers at Karolinska Institutet have now found specific markers on the surface of the RPE cells that can be used to isolate and purify these retinal cells. The results are published in Nature Communications.

"The finding has enabled us to develop a robust protocol that ensures that the differentiation of embryonic stem cells into RPE cells is effective and that there is no contamination of other cell types," says principal investigator Fredrik Lanner, researcher at the Department of Clinical Science, Intervention and Technology and the Ming Wai Lau Center for Reparative Medicine at Karolinska Institutet. "We've now begun the production of RPE cells in accordance with our new protocol for the first clinical study, which is planned for the coming years."

One obstacle when transplanting tissue generated from stem cells is the risk of rejection, which occurs if transplantation antigens of the donor and patient tissue differ. Research groups around the world are therefore working on creating what are known as universal cells, which ideally will not trigger an immune response.

In a study published in Stem Cell Reports the same group at Karolinska Institutet created embryonic stem cells able to hide from the immune system. Using CRISPR/Cas9 gene editing, they removed certain molecules, HLA class I and class II, which sit on the surface of the stem cells as a means by which the immune system can identify them as endogenous or not. The stem cells lacking these molecules were then differentiated into RPE cells.

The researchers have been able to show that the modified RPE cells retain their character, that no harmful mutations appear in the process and that the cells can avoid the immune system's T cells without activating other immune cells. The rejection response was also significantly less and more delayed than after the transplantation of regular RPE cells, the surfaces of which still possess HLA molecules.

"The research is still in an early stage, but this can be an important initial step towards creating universal RPE cells for the future treatment of age-related macular degeneration," says joint last author Anders Kvanta, adjunct professor at the Department of Clinical Neuroscience and consultant at St Erik Eye Hospital.
-end-
The study was financed by the Ming Wai Lau Centre for Reparative Medicine, the Knut and Alice Wallenberg Foundation, the Centre for Innovative Medicine, the Swedish Research Council, the Ragnar Söderberg Foundation, the Wallenberg Academy Fellows programme, the Swedish Foundation for Strategic Research, Region Stockholm (ALF funding), Karolinska Institutet, Ögonfonden, the Cronqvist Foundation, the Strategic Research Programme in Stem Cells and Regenerative Medicine, Crown Princess Margareta Foundation for the Visually Handicapped, the ARMEC Lindeberg Foundation, the Ulla and Ingemar Dahlberg Foundation and the King Gustaf V and Queen Victoria Foundation.

Publications:

"Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells". Alvaro Plaza Reyes, Sandra Petrus-Reurer, Sara Padrell Sánchez, Pankaj Kumar, Iyadh Douagi, Hammurabi Bartuma, Monica Aronsson, Sofie Westman, Emma Lardner, Helder André, Anna Falk, Emeline F. Nandrot, Anders Kvanta, Fredrik Lanner. Nature Communications, online 30 March 2020, doi: 10.1038/s41467-020-15326-5

"Generation of retinal pigment epithelial cells derived from human embryonic stem cells lacking human leukocyte antigen class I and II". Sandra Petrus-Reurer, Nerges Winblad, Pankaj Kumar, Laia Gorchs, Michael Chrobok, Arnika Kathleen Wagner, Hammurabi Bartuma, Emma Lardner, Monica Aronsson, Álvaro Plaza Reyes, Helder André, Evren Alici, Helen Kaipe, Anders Kvanta, Fredrik Lanner. Stem Cell Reports, online 19 March 2020, doi: 10.1016/j.stemcr.2020.02.006.

Karolinska Institutet

Related Stem Cells Articles:

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.