Are stem cells the future for treating macular degeneration?
in Clinical Trials, Macular Degeneration, News
17 Apr 2015
Stem cells are undifferentiated biological cells that can grow indefinitely with an ability to turn into any type of cells in the body (this ability is called pluripotency).
Stem cell research, especially human embryonic stem cell research, holds great potential to treat many diseases such as cancer and diseases in central and peripheral nerve system. However, there are considerable ethical concerns around the use of human embryos.
In 2006, Prof. Shinya Yamanaka at Kyoto University in Japan, found a way to make induced pluripotent stem cells (iPS cells) by reprogramming the skin cells of adult mice with specific genomic factors (so called Yamanaka factors: OCT4, SOX2, KLF4, and c-MYC).
Shortly after the successful animal experiments, he successfully made human iPS cells from human adult skin cells and won a Nobel Prize in 2012 as a result.
iPS cells began a new era of stem cell research because they have many of the characteristics of embryonic stem cells whilst avoiding ethical concerns as the cells come from the patient.
This also means that they will not be rejected if they are grafted back for example as nerve cells into the brain or the retina.
In the future, iPS cells may be used to treat diseases in a variety of ways. They may be used to replace cells that have worn out.
Transplanting photoreceptors is something we hope to do in future, although we will also need to transplant retinal pigment epithelial cells to support the photoreceptors. It’s a bit tricky and we are certainly still several years away from clinical use.
Another potential clinical use of iPS cells is to replace genetically defective cells with freshly made cells where the genetic defect has been repaired.
The other use of iPS cells are to model disease in a dish in order to understand the disease better and potentially find new treatments. This is what we are doing.
One recent report that has moved the field forward more quickly than expected is that iPS cells can be induced by applying the right factors at the right time to actually assemble retinas in a dish.
Use of iPS cells in Macular Telangiectasia Type 2
We are using this cutting edge iPS cell technology in our laboratory to investigate potential causes and future treatments for macular degeneration. As we have written in previous editions of MaculaNews, we believe that a deficiency of Muller cells, the major supporting cells nurturing other neurons, may contribute to macular degeneration. If we can identify what this is we might find a better treatment.
In our laboratory, we are currently using iPS cells from patient skin biopsy samples to model macular degeneration in a dish.
We have obtained patient skin biopsy samples from Prof. Mark Gillies clinic and successfully reprogrammed them into iPS cells with Yamanaka factors in collaboration with an internationally recognized stem cell research group, Dr. Alice Pebay’s laboratory, at the Centre for Eye Research Australia in Melbourne.
Our goal is to differentiate patient derived iPS cells into retinal cups in the laboratory and isolate Muller cells from the retinal cups.
After this, we will study the Muller cells to understand what is wrong with them and how it might be fixed.
Figure 1*: shows how induced pluripotent cells are made from a patient’s skin biopsy and what they can be used for. Cells taken from the skin biopsy are grown in a dish. They are then turned into stem cells using “reprogramming factors”, which is a major scientific advance. If the cells are taken from patients with a disease caused by a single gene defect, this can be corrected and the cells can theoretically be put back into the body to replace the diseased cells. This is already starting for some diseases, but most macular diseases cannot yet be treated in this way because they are caused by a combination of many gene defects which are not yet completely understood. The other use is that the cells presumably have the same defect as the patient, because that is where they came from. So they can be studied in a dish and tested in various ways to find out what is causing the disease. This is what we are trying to do for macular disease. We also intend to develop the cells into the various cell types that make up the retina and put them back in the patient’s retina, but that is a long-term vision. *iPS cells derivation and its applications (http://www.eurostemcell.org/factsheet/ips-cells-and-reprogramming-turn-any-cell-body-stem-cell)
Figure 2: shows the progress we have made so far in making these iPC stem cells. (A) shows the cells grown from the skin biopsy of a patient with macular disease. They were reprogrammed to produce stem cells, which can be seen as little islands, each of which has grown from a single stem cell (B). These “clones” are grown up to produce a cell “line” which has come from a single stem cell (C). The middle row shows cells from one of our patients “stained” with coloured antibodies that detect the stem cell markers shown, demonstrating that they really are stem cells. In the third row are 2 stem cell clones from a second patient with macular disease that are positive for the same stem cell markers.