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العنوان
Role of Stem Cell Therapy for
Retinal Degeneration
المؤلف
Hussein Shaker El Markaby,Mohamed
هيئة الاعداد
باحث / Mohamed Hussein Shaker El Markaby
مشرف / Osama Salem
مشرف / Mohamed Moghazi
الموضوع
FUTURE of STEM IN RETINAL DEGENERATION.
تاريخ النشر
2008 .
عدد الصفحات
93.p؛
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب العيون
تاريخ الإجازة
1/1/2008
مكان الإجازة
جامعة عين شمس - كلية الطب - Ophthalmology
الفهرس
Only 14 pages are availabe for public view

from 94

from 94

Abstract

Confusingly there are many different cells encompassed by the term stem cell. Each has different properties, functions and living environments. Additionally, different stem cells exist at various time points during an individual’s lifespan, from conception to old age. This means that stem cells can be routinely found in embryos, fetuses and adults. All these stem cells have in common the capability to extensively multiply long-term, producing more identical stem cells - a process called self-renewal. Also, whilst stem cells themselves are unspecialized, they can produce cells, such as retinal photoreceptors or other characteristic cells of the body, which adopt specialized shapes and functions - such specialization is called differentiation.
Why might stem cells be useful for treating retinal degenerations?
In some retinal diseases, photoreceptor cells die due to an intrinsic abnormality and/or due to disruption or death of supportive cells in the retinal pigment epithelium. However some other parts of the body can cope with similar cell death. This is because other existing cells in the tissue can divide in a regulated way to create new cells that replenish the remaining stock. Unfortunately, this is not the case for mature retinal photoreceptors. This is why stem cells might be very handy, because some of them do have the capacity to divide and form new photoreceptors. It is therefore hoped that they might be harnessed in the future to replenish the ailing retina of its photoreceptors.
How might stem cells be used to treat retinal diseases?
They could be surgically transplanted into the eye or drugs could be developed to activate suitable populations of stem cells naturally present within the patient’s body. With respect to transplantation, stem cells may be triggered to partially or fully specialize into photoreceptors in the laboratory before being transplanted into the eye. Once in the retina it is hoped that the new retinal cells will mature and incorporate within the existing tissue. This process may be helped naturally by the degenerating retina, which emits signals into the local environment of the eye, to indicate its state of damage.
If the aim is to replace photoreceptors, why use stem cells? Wouldn’t it be better to transplant photoreceptors directly?
As some readers may be aware, there is ongoing research into the benefits of directly transplanting healthy photoreceptors taken from donor eyes. In fact, in animal models of retinal degeneration, such transplants have been observed to restore retinal structure somewhat. However even if this approach can be perfected and shown to significantly restore vision in humans, there is one major problem. Just as the number of people requiring donor hearts far exceeds the number of organs available for transplantation, it is likely that more patients would benefit from retinal cell transplantation than available quantities of donor eye tissue will support.
Unlike photoreceptor cells, stem cells can be helped to divide many times in the laboratory, thereby expanding the number of cells available for transplant and providing for the treatment of more patients. Stem cells can often be kept expanding for lengthy periods of time in the laboratory and they might therefore represent a renewable source of replacement cells. This is analogous to the description of wood as a renewable energy source. A well managed forest will grow enough new trees to replace those felled for use; a well managed stock of stem cells may grow enough new cells to replace those taken for transplantation.
In addition to this, it is possible that transplanted stem cells and the very immature photoreceptors they give rise to, might be able to integrate into their new host retina more easily and successfully than mature specialized cells. This is similar to the notion that, given time, a young child often integrates more easily into a new country than his/her older relatives. It is likely that optimal levels of cell specialization and maturation will need to be established for transplant and this could vary for different retinal diseases such as RP and ARMD.
Would there be any risks or side effects associated with stem cell therapy?
Of course it is not possible to fully anticipate side effects without actually testing procedures in humans. However as with any treatment there are potential risks involved:
During any transplantation procedure, there is the possibility of excessive surgical damage occurring to the eye.
As previously mentioned unspecialized stem cells, especially embryonic stem cells have the potential to cause tumours when transplanted.
As with any transplant procedure, there is always the possibility of the cells acting as vectors for infectious diseases. However this should be a minimal risk in most cases, as long as donor cells are properly screened prior to use one particular worry is that virtually all human embryonic stem cells have been grown in contact with a special type of mouse cell, which feeds the stem cells essential products. It is possible that such stem cells might carry animal viruses transferred from the mouse cells and these obviously must not be allowed to pass into humans. To avoid this, embryonic stem cells can be grown with special cells of human origin, which feed the stem cells with equivalent products to mouse cells. Another option is to grow embryonic stem cells with artificial alternatives to feeder cells.
What about gene therapy, will that be abandoned?
Definitely not. Many researchers still hold great hope that gene therapy will someday be effectively applied to a number of retinal degenerative diseases in humans. Despite their great potential, for the time being, stem cells are just another avenue of research and there are still many problems to be tackled, some of which have been pointed out in this article. What is more, stem cells and gene therapy may team up to make the ultimate disease busting combination. The ability of stem cells to self-renew is also helpful in this regard; stem cells can be genetically modified so that they make the specific product of choice (e.g. a photoreceptor survival-
Promoting factor) and because they self-renew they reduce the need for repeated cycles of gene therapy. Additionally stem cells often have the ability to zero in on specific sites within an organ. It may so happen that some of these sites are good tactical localities for targeted administration of therapeutic agents. For example in both RP and ARMD specific blood vessel abnormalities can arise, therefore retinal blood vessels represent one potentially good target site in some patients.
So should I be optimistic?
Yes! None of the problems facing stem cell research are insurmountable. They will however take time and money to solve. New findings turn up on a weekly basis in this field and more researchers are being attracted to work on stem cells all the time; progress will only accelerate in the coming months.

In Short
The good news is that the retina is one of the best targets for stem cell therapy in the human nervous system.
However restoring proper, sight-imparting function to the failing retina remains a formidable goal; stem cells are promising, not miraculous. It will be several years before stem cell therapy is used in human retinal dystrophy patients.