Wetenschappers hebben in een experiment menselijk netvlies uit stamcellen gekweekt. Dit geeft hoop aan honderdduizenden patiënten met maculadegeneratie. Wetenschappers van de John Hopkins University School of Medicine stellen dat deze doorbraak, die het gevolg is van groeiend weefsel op een petrischaaltje, het zicht kan herstellen bij mensen die lijden aan verschillende netvliesaandoeningen.

Onderzoekers waren in staat om een lichtgevoelige netvlies te laten groeien door volwassen stamcellen te gebruiken en ze terug naar een embryonale staat te herprogrammeren. Onderzoeksleider dr. Valeria Canto-Soler zegt: “We hebben in feite een miniatuur menselijk netvlies in een schaaltje gecreëerd dat niet alleen gebouwd is als een netvlies, maar ook het vermogen heeft om licht te detecteren.

“Dit project biedt opties voor zichtreddend onderzoek en kan uiteindelijk leiden tot technologieën om het zicht te herstellen bij mensen met netvliesaandoeningen.” Het netvlies is de laag van lichtgevoelige cellen en neuronen aan de achterkant van het oog dat lichtsignalen omzet in zenuwboodschappen die worden verzonden naar de hersenen.

Tijdens het experiment kon het team van Dr Canto-Soler de initiële groei van het netvlies stimuleren waarna deze zich verder ontwikkelde. “Toen we aan dit project begonnen, dachten we niet dat stamcellen in staat zouden zijn om bijna zelfstandig een netvlies op te bouwen” zegt Dr Canto-Soler. “In ons systeem wisten de cellen op de één of andere manier wat ze moesten doen.”

De wetenschappers testten het mininetvlies door deze bloot te stellen aan lichtimpulsen. Dit gebeurde in een fase die overeenkomt met de foetale ontwikkeling van 28 weken. Hieruit bleek dat de in het laboratorium gegroeide fotoreceptoren op dezelfde manier op licht reageerden als in het menselijk oog.

Dr Canto-Soler, wiens onderzoek is gepubliceerd in Nature Communications, zegt dat de techniek de mogelijkheid geeft om honderden mininetvliezen te genereren wanneer een persoon getroffen is een oogaandoening waardoor hij blind wordt. Deze kunnen gebruikt worden om de oorzaken van netvliesaandoeningen in menselijk weefsel te bestuderen, in plaats van te vertrouwen op diermodellen.

Op de structuren kan ook medicatie op maat van de individuele patiënt worden getest. Op lange termijn kunnen zieke of dode netvliesweefsels vervangen worden en kan het zicht hersteld worden door de in het laboratorium gekweekte cellen, voegt Dr Canto-Soler er aan toe. Leeftijdsgebonden maculadegeneratie, die wordt veroorzaakt door een netvliesprobleem, is debelangrijkste oorzaak van slechtziendheid in het Verenigd Koninkrijk. Daar lijden zo’n 500.000 mensen aan de oogaandoening volgens de NHS cijfers.

De oogziekte komt het meest voor bij mensen boven de 50. 1 op de 10 mensen boven 65 jaar lijdt tot op zekere hoogte aan de aandoening.

Stem cell researchers are making great progress in their efforts to replace the RPE layer, which they believe will halt or even reverse the vision loss associated with AMD.

Some researchers are using induced pluripotent stem (iPS) cells — tissue-specific cells (usually skin cells, but sometimes other tissue cells) that are reprogrammed in the lab to behave like embryonic stem cells – to grow rods and cones or RPE cells. Other groups are using human embryonic stem cells, and others are exploring RPE-specific stem cells that can be grown from the adult RPE, for example, from eyes donated to eye banks.

Researchers are working to determine the optimal maturation for these cells. The more mature (that is, more differentiated) the cells are when transplanted, the less likely they are to over-grow (to generate too many RPE cells, which can lead to scar tissue) or to migrate away from their intended place in the body. On the other hand, less mature cells have more self-renewal properties and possibly more potential to integrate and repair the eye’s rods and cones.

Researchers are also exploring different methods to deliver stem cells to the eye, including creating patches of RPE cells in the lab. In one approach, a one-cell-thick layer of RPE cells derived from human embryonic stem cells or adult RPE stem cells is placed on a material that allows nutrients and waste materials to pass through and is implanted in the eye. In tests in animals, the patch has shown promise; the RPE cells appear to be stable and don’t migrate to other areas of the eye.

Another delivery showing promise is a suspension of cells, which is injected into the eye under the retina. The cells, derived from iPS cells, RPE stem cells, or human embryonic stem cells, are grown and differentiated in the lab, then placed in a harmless fluid to be injected.

For both approaches, a critical question is whether these cells will integrate well with the patient’s own RPE cells and do their job of supporting the rods and cones over the long term.

https://www.closerlookatstemcells.org/stem-cells-and-medicine/macular-degeneration

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Posted on 9/30/2015

by Maureen Duffy

A pioneering clinical trial of a new treatment derived from embryonic stem cells for people with wet age-related macular degeneration (AMD) has been initiated at Moorfields Eye Hospital in London, following a successful operation on a 60-year-old woman. She is the first of 10 persons with wet AMD who will receive the stem cell treatment as part of an 18-month clinical trial to test the safety and effectiveness of this procedure.

In the United States, Ocata Therapeutics has revealed positive results from its small (18-patient) early-stage clinical trials of human embryonic stem cells (hESC) for the treatment of dry age-related macular degeneration and Stargardt disease.

Nevertheless, despite these encouraging – although admittedly very early – results, a clinical trial for stem cell treatment of wet AMD has remained elusive – until now.

This initial operation is a key component of the London Project to Cure Blindness, which was established ten years ago with the goal of curing vision loss in persons with wet AMD. The Project is the result of a partnership that includes Moorfields Hospital, the University College London (UCL) Institute of Ophthalmology, the National Institute for Health Research, and Pfizer Inc.

The London Project to Cure Blindness

Excerpted from About Us at the London Project to Cure Blindness website:

The London Project to Cure Blindness has, for the past 10 years, been developing cell-based treatments to cure blindness associated with age-related macular degeneration (AMD). The group has been culturing embryonic stem cells, which give rise to all human cell types, to grow patches of retinal cells for transplant.

The project aims to bring stem cell therapy for retinal diseases, especially for AMD, to the clinic as rapidly as possible. We believe stem cell-based therapies for these conditions have the greatest chances of preventing blindness, restoring sight, and improving quality of life in the future.

The stem cell approach aims to replace cells in the eye that are either damaged or missing. In AMD the main cells that are initially affected are the retinal pigment epithelium cells (RPE). In the first of the trials developed by the London Project, we are using human embryonic stem cells (hES) that have been transformed into RPE cells. These RPE cells will then be transplanted under the patient's retina on a specially engineered patch that the London Project has developed.

[Editor's note: Retinal pigment epithelium (RPE) cells are the deepest cells of the retina. The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These photoreceptor cells are triggered by light to set off a series of electrical and chemical reactions that helps brain to interpret what the eye sees. The degeneration of the RPE cells also leads to the death of the rods and cones and, ultimately, vision.]

More recently, The London Project has secured funding to examine the use of induced pluripotent stem cell (iPSC) technology for transplantation. This allows the original cells to be taken from the person with the disease themselves and not from another source, such as an embryo.

[Editor's note: Pluripotent refers to a stem cell that has the power to develop into any type of bodily cell or tissue ("pluri" = many; "potent" = having power). An induced pluripotent stem cell (iPSC) is a type of pluripotent stem cell that can be generated directly from adult cells.]

Another important arm of the project is to develop the technology by which stem cells can be transformed into photoreceptors (primarily cones and rods) and transplanted into patients. It is believed that the photoreceptors are lost after the RPE cells have degenerated.

This first clinical trial, which has been granted permission by the UK regulatory authority, will be for severe wet degeneration, and if successful, will then be also used in dry macular degeneration.

More about the Stem Cell Clinical Trial

The ongoing clinical trial at Moorfields Eye Hospital in London is investigating the safety and effectiveness of transplanting RPE cells derived from stem cells to treat people with sudden severe visual loss from wet AMD. These cells are used to replace those at the back of the eye that are diseased in AMD. This is done using a specially engineered patch inserted behind the retina in an operation lasting one to two hours.

In total, the trial will recruit 10 patients over a period of 18 months. Each patient will be followed for a year to assess the safety and stability of the cells and the degree to which their vision is restored.

The first surgery was performed in August 2015 and there have been no reported complications to date. The surgical team hopes to determine the outcome, in terms of initial visual recovery, by early December 2015.

http://www.visionaware.org/blog/visionaware-blog/the-first-stem-cell-clinical-trial-for-wet-macular-degeneration-is-underway-in-london-2093/12

Clinical Trials for Dry AMD

Clinical trials are the final research phase before a treatment is approved for the general public. 

Research on treatments starts in the laboratory where scientists work to identify the processes involved. These are called Pre-Clinical studies.

Clinical trials begin with Phase I trials, which test the treatment on a small number of people for safety and best dose.

Phase II involves several hundred subjects to test for effectiveness.

Phase III expands the study to thousands of people in order to confirm effectiveness and monitor safety and side effects.

After the drug or treatment has been approved by the Food and Drug Administration (FDA) and made available for public use, studies continue to track side effects and success.

These clinical trials are recruiting patients to volunteer.  Participants in any clinical trial are chosen based on eligibility.  If you are interested in participating, ask your retinal specialist if you would be a good candidate.  Or, use the information in each section to contact the coordinator of the trial.  Some of these clinical trials have many sites throughout the U.S.  Others are in one location in the U.S. or in other countries.  You will always need to be examined before you are accepted and you must be available for appointments.

Clinical trials listed below are divided into three time frames. The first are the Clinical Trials that are still “Recruiting” patients to participate in the study. The second are the Trials that are currently in progress, but are “Not Recruiting” new patients. The last and final stage are those studies that are “Completed” already and have some results to report.

http://www.amd.org/what-is-macular-degeneration/dry-amd/clinical-trials-for-dry-amd/