Use of stem cells derived from Wharton’s jelly in Retinitis Pigmentosa Treatment

Retinitis Pigmentosa otherwise tapetoretinal degeneration of the retina is a rare disease, occurring with a frequency 1 out of 4000 births. In Poland there is about 15,000 people suffer from it although no accurate statistics are available.
The essence of the disease is the disappearance of photoreceptors that is, cells capable of processing visual signals into electrical signals transmitted to the brain. There are two types of photoreceptors – rod cells and cone cell. Atrophy starts with rod cells, which are responsible for seeing at dusk and in the dark. As more cells die, patients’ vision narrows up to maintaining the island of central vison consisting mainly of cone cells. Cone cells are photoreceptors responsible for the ability to see details, colors, enabling us to read and perform precise activities. In the majority of patients with Retinitis Pigmentosa cone cells start to die in a later age, with an exception of one type of a Retinitis Pigmentosa otherwise called Rod – Cone Dystrophy where cone cells die first and later rod cells.
In Retinitis Pigmentosa, beside the photoreceptors atrophy, we encounter subcapsular cataract in 39-72% of the cases, and in 30% of the cases a hearing impairment not connected to the Usher Syndrome.
Due to the nature of the disease, the first difficulties appear in childhood, especially at dusk and at night. Parents notice that with a little light a child cannot find certain objects or perform certain tasks. For example a child cannot find a way to the bathroom at night in a strange place.
The most severe form of Retinitis Pigmentosa is Leber’s congenital amaurosis, in which both types of photoreceptors – cone cells and rod cells are attacked simultaneously.
Ways of inheriting
Retinitis Pigmentosa is a group of genetically transmitted diseases, although there are sporadic cases where no one of the ancestors was ill before. Retinitis Pigmentosa can rarely be part of syndromes that is situations in which the eye symptoms are accompanied by other diseases. The syndromes most often accompanied by Retinitis Pigmentosa is the Usher Syndrome (eye symptoms co-occur with partial hearing loss), the Bardet–Biedl syndrome and the Refsum disease.
There are 4 ways of inheritance and all of them may occur in Retinitis Pigmentosa:
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- Autosomal dominant, ADRP, where regardless of the genetic material of the other person 100% children will be affected.
- Autosomal recessive, ARRP, where there are 50% risk that the child will become ill.
- Linked to X chromosome, XLRP and two-hybrid, where the women are the carriers and mostly men get ill. It is believed that about 20% of women can nevertheless get sick, although the disease has a milder course than with men.
- Mitochondrial and non-genetic, so called sporadic – in those cases it is difficult to define the percentage in which the disease is transferred onto the offspring. Retinitis Pigmentosa is a first case in a family in 10% to 40%.
To understand how difficult it is to diagnose and treat Retinitis Pigmentosa is to realize that so far 150 genetic mutations have been discovered.
So much variation in the way of inheritance makes it very difficult to diagnose, because even genetic testing does not guarantee answers to all the questions. Partially it is due to the costs of testing such a big number of genes, and partially due to inability of isolating all damaged genes, because – as I wrote before – in Retinitis Pigmentosa, spontaneous gene mutations are possible.
What are stem cells?
Many myths and inaccuracies surround stem cells. First of all we need to understand that stem cells are not one kind of cells but many. Among stem cells there are undifferentiated embryonic cells and mesenchymal stem cells, which are currently intensively studied and used mainly in clinical trials and scientific experiments. Mesenchymal stem cells can be grown from three sources: from bone marrow, body fat or from the umbilical cord, specifically from the connective tissue surrounding blood vessels called Wharton’s jelly.
All techniques are based on isolating stem cells and then stimulating its multiplication, independently from the type of tissue used to produce them. For example it takes two months to grow stem cells from Wharton’s jelly from the moment of the umbilical cord extraction to the final product.
It needs to be stressed that in case of the mesenchymal stem cells there are no problems of ethical nature, as is the case of undifferentiated human embryonic cells.
It is also possible to transplant cells between different people without a risk of a transplant rejection. It is because stem cells are nearly invisible to the immune system.
In what way a stem cell therapy can help patients with Retinitis Pigmentosa?
Mesenchymal stem cells should be treated as an additional secretory gland, which under certain conditions produces substances that improve blood circulation, acts anti-inflammatory and also promotes regeneration. Mesenchymal stem cells have antineoplastic effect. Beside a therapeutic effect, based on a change of the cellular environment and directing affected cells toward proper functioning, stem cells can also transform into other cells. It needs to be stressed that quantity of cells, which transform into missing cells is small. Animal testing has shown that newly created cells have properties of the missing nerve cells and are capable of secretion of typical to them substances. It is not known whether newly created cells are able to create synapses or connections between nerve cells. In case of complex tissues, such as retina, recreating all the cells’ layers is not possible at the present stage of knowledge. For now we concentrate our efforts on the most affected layer of photoreceptors and located under it the retina’s dye epithelium.
In regenerative therapy of the retina there are also attempts of implanting stem cells transferred into photoreceptors, replacing damaged cells with new ones. Outcomes of those experiments are not available yet, although a problem is a survival of the new layer of cells and its connection with host cells. In this case the difference is based on a way we use stem cells. After isolating stem cell, we grow from it for example – photoreceptors and only then transplant them under the retina.
How is it done?
Stem cells can be transplanted into different parts of the eye. All methods require surgery under operating room conditions. In some of the cases a surgical removal of the vitreous is necessary. Stem cells can be transplanted into:
– vitreous chamber,
– subretinal space,
– in front of the edema,
– in front of the optic nerve,
– into the muscle cone that surrounds optic nerve connecting the eye with the brain.
Even though there are no exact tests on stem cells survival time in human eye, it is believed that they survive for a few months. During that time they produce regenerative substances, gather where inflammatory processes are, and influence cells’ metabolism.
Switching damaged cells to new metabolic pathways improves their functioning, as well as stops degenerative processes in tissues surrounding damaged cells.
Future?
Although in most patients the vision improves, we do not know how long it will last. Undoubtedly there is a temporary stop of retinal degradation. But the future of cells’ therapy will depend on a discovery of a way to control connections between different types of cells, which will allow recreating such complex structures as retina. Undoubtedly a creation of safe ways of implanting stem cells into the eye and keeping them alive, so they can become part of the new host’s body, will be needed.