Restoring Vision with Stem Cells

Researchers have succeed in producing photoreceptors from human embryonic stem cells

Tuesday, 06 October 2015

Age-related macular degeneration (AMRD) could be treated by transplanting photoreceptors produced by the directed differentiation of stem cells, thanks to findings published today by Professor Gilbert Bernier of the University of Montreal and its affiliated Maisonneuve-Rosemont Hospital. ARMD is a common eye problem caused by the loss of cones. Bernier's team has developed a highly effective in vitro technique for producing light sensitive retina cells from human embryonic stem cells.

"Our method has the capacity to differentiate 80% of the stem cells into pure cones," Professor Gilbert explained.

"Within 45 days, the cones that we allowed to grow towards confluence spontaneously formed organised retinal tissue that was 150 microns thick. This has never been achieved before."

In order to verify the technique, Bernier injected clusters of retinal cells into the eyes of healthy mice. The transplanted photoreceptors migrated naturally within the retina of their host.

Age-related macular degeneration could be

treated by transplanting photoreceptors

produced by the directed differentiation of stem

cells, thanks to findings published today by

Professor Gilbert Bernier of the University of

Montreal and its affiliated Maisonneuve-

Rosemont Hospital. This image illustrates the 3D

reconstruction of the tissue that was produced in

vitro and labelled with antibodies against

photoreceptor-specific proteins. Credit: G.

Bernier, Université de Montréal.

"Cone transplant represents a therapeutic solution for retinal pathologies caused by the degeneration of photoreceptor cells," Bernier explained.

"To date, it has been difficult to obtain great quantities of human cones."

His discovery offers a way to overcome this problem, offering hope that treatments may be developed for currently non-curable degenerative diseases, like Stargardt disease and ARMD.

"Researchers have been trying to achieve this kind of trial for years," he said.

"Thanks to our simple and effective approach, any laboratory in the world will now be able to create masses of photoreceptors. Even if there's a long way to go before launching clinical trials, this means, in theory, that will be eventually be able to treat countless patients."

The findings are particularly significant in the light of improving life expectancies and the associated increase in cases of ARMD. ARMD is in fact the greatest cause of blindness amongst people over the age of 50 and affects millions of people worldwide. And as we age, it is more and more difficult to avoid - amongst people over 80, this accelerated aging of the retina affects nearly one in four. People with ARMD gradually lose their perception of colours and details to the point that they can no longer read, write, watch television or even recognize a face.

ARMD is due to the degeneration of the macula, which is the central part of the retina that enables the majority of eyesight. This degeneration is caused by the destruction of the cones and cells in the retinal pigment epithelium (RPE), a tissue that is responsible for the reparation of the visual cells in the retina and for the elimination of cells that are too worn out. However, there is only so much reparation that can be done as we are born with a fixed number of cones. They therefore cannot naturally be replaced. Moreover, as we age, the RPE's maintenance is less and less effective - waste accumulates, forming deposits.

"Differentiating RPE cells is quite easy. But in order to undertake a complete therapy, we need neuronal tissue that links all RPE cells to the cones. That is much more complex to develop," Bernier explains, noting nonetheless that he believes his research team is up to the challenge.

Bernier has been interested in the genes that code and enable the induction of the retina during embryonic development since completing his PhD in Molecular Biology in 1997.

"During my post-doc at the Max-Planck Institute in Germany, I developed the idea that there was a natural molecule that must exist and be capable of forcing embryonic stem cells into becoming cones," he said.

Indeed, bioinformatics analysis led him to predict the existence of a mysterious protein: COCO, a "recombinational" human molecule that is normally expressed within photoreceptors during their development.

In 2001, he launched his laboratory at Maisonneuve-Rosemont Hospital and immediately isolated the molecule. But it took several years of research to demystify the molecular pathways involved in the photoreceptors development mechanism. His latest research shows that in order to create cones, COCO can systematically block all the signalling pathways leading to the differentiation of the other retinal cells in the eye. It's by uncovering this molecular process that Bernier was able to produce photoreceptors. More specifically, he has produced S-cones, which are photoreceptor prototypes that are found in the most primitive organisms.

Beyond the clinical applications, Professor Bernier's findings could enable the modelling of human retinal degenerative diseases through the use of induced pluripotent stem cells, offering the possibility of directly testing potential avenues for therapy on the patient's own tissues.

Source: University of Montréal

Contact: William Raillant-Clark

Reference:

Differentiation of human embryonic stem cells into cone photoreceptors through simultaneous inhibition of BMP, TGFβ and Wnt signaling

Shufeng Zhou, Anthony Flamier, Mohamed Abdouh, Nicolas Tétreault, Andrea Barabino, Shashi Wadhwa and Gilbert Bernier

Development, 42, 3294-3306, October 1, 2015, doi: 10.1242/dev.125385

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Tumour Suppressor Also Inhibits Key Property of Stem Cells

Tumour Suppressor Also Inhibits Key Property of Stem Cells

Friday, 14 November 2014

A protein that plays a critical role in preventing the development of many types of human cancers has been shown also to inhibit a vital stem cell property called pluripotency, according to a study by researchers at the Stanford University School of Medicine.

Blocking expression of the protein, called retinoblastoma, in mouse cells allowed the researchers to more easily transform them into what are known as induced pluripotent stem cells, or iPS cells. Pluripotent is a term used to describe a cell that is similar to an embryonic stem cell and can become any tissue in the body.

The study provides a direct and unexpected molecular link between cancer and stem cell science through retinoblastoma, or Rb, one of the best known of a class of proteins called tumour suppressors. Although Rb has long been known to control the rate of cell division, the researchers found that it also directly binds and inhibits the expression of genes involved in pluripotency.

"We were very surprised to see that retinoblastoma directly connects control of the cell cycle with pluripotency," said Julien Sage, PhD, associate professor of paediatrics and of genetics.

"This is a completely new idea as to how retinoblastoma functions. It physically prevents the reacquisition of stem cell-ness and pluripotency by inhibiting gene expression."

"The loss of Rb appears to directly change a cell's identity. Without the protein, the cell is much more developmentally fluid and is easier to reprogram into an iPS cell," said Marius Wernig, MD, associate professor of pathology.

Wernig and Sage, both members of the Stanford Cancer Institute, share senior authorship of the study, which will be published online Nov. 13 in Cell Stem Cell. Postdoctoral scholar Michael Kareta, PhD, is the lead author.

Tumour Suppressor

Pluripotent stem cells are able to become any tissue in the body. In 2006, researchers in Shinya Yamanaka's laboratory in Kyoto University found that it's possible to push a fully specialized adult cell, such as a skin cell, backward along the developmental pathway to assume a pluripotent state. They did so by adding four proteins – Sox2, Oct4, c-Myc and Klf4 – that are normally found in cells only very early in embryonic development. The resulting cells were called induced pluripotent stem cells.

Rb was first identified as a tumour suppressor because of its role in a rare but rapidly developing childhood cancer of the retina. It has since been shown to be missing or functionally inactive in nearly all human cancers. Intact Rb prevents cancer by acting as a natural brake on the cell cycle, the process by which cells divide to make daughter cells. Loss of Rb allows a cell to divide more quickly and potentially accumulate more cancer-causing mutations. However, the new research shows that Rb's effect on pluripotency is independent of its role in cell cycle control.

Cancerous cells often appear less mature than their noncancerous peers. They persist in dividing in the face of external cues that curb the proliferation of normal cells, and they often seem to regress developmentally, assuming the form and mimicking the behaviour of their more developmentally flexible ancestors. A similar cascade of events occurs when researchers create iPS cells from specialized adult cells.

"The process of creating iPS cells from fully differentiated, or specialized, cells is in many ways very similar to what happens when a cell becomes cancerous," said Sage, who holds the Harriet and Mary Zelencik Endowed Professorship in Pediatrics.

"We wondered if we could learn more about both processes by investigating whether the loss of Rb affects reprogramming efficiency."

Previous studies in other laboratories have suggested that Rb may also be involved in promoting cellular differentiation – a cell's developmental progression toward a more specialized state.

Link between Rb and Pluripotency

The researchers found that embryonic mouse cells unable to express functional Rb were much more efficiently and quickly converted to iPS cells than were cells in which Rb was present. Conversely, cells with higher-than-normal levels of the Rb protein were more difficult to reprogram into iPS cells. When the researchers compared the rate of division of the control cells with those in which Rb expression was lost, they found no significant differences.

"It didn't change the cell proliferation rates at all," said Wernig.

"This indicated that Rb's mechanism of action on reprogramming was something completely different than what we had expected."

Further investigation showed that Rb directly binds to many genes involved in the acquisition of pluripotency, including those encoding two of the proteins often used by researchers to create iPS cells: Sox2 and Oct4. Loss of Rb increased the expression of the proteins, thereby affecting a large "pluripotency network."

"We saw a global effect on a network of genes involved in pluripotency," said Sage.

The net effect, according to the researchers, is an overall reduction in the natural barrier that exists to prevent specialized adult cells from dedifferentiating – that is, spontaneously becoming pluripotent, an occurrence that could easily wreak havoc on a multicellular organism that depends on an orderly arrangement of tissues.

The researchers also showed that Rb's effect on the pluripotency network is an important driver of cancer in a mouse model. Animals in which Rb expression is blocked typically develop pituitary tumours within a few months. However, the researchers found the cancers didn't occur when Sox2 was also removed.

"It's clear that Sox2 expression is also required for the development of cancers in the animals," said Wernig.

"This implies that Rb's effect on Sox2 expression is critical for cancer development."

The researchers plan to continue their investigations into the relationship between Rb and pluripotency. In particular, Wernig is interested in learning whether Rb expression plays a role in a phenomenon he discovered called direct conversion, in which one cell type, such as a skin cell, can be directly converted into another, such as a neuron, without first entering a pluripotent state.

Source: Stanford University Medical Center

Contact: Krista Conger

Reference:

Inhibition of Pluripotency Networks by the Rb Tumor Suppressor Restricts Reprogramming and Tumorigenesis

Michael S. Kareta, Laura L. Gorges, Sana Hafeez, Bérénice A. Benayoun, Samuele Marro, Anne-Flore Zmoos, Matthew J. Cecchini, Damek Spacek, Luis F.Z. Batista, Megan O’Brien, Yi-Han Ng, Cheen Euong Ang, Dedeepya Vaka, Steven E. Artandi, Frederick A. Dick, Anne Brunet, Julien Sage, Marius Wernig

Cell Stem Cell, November 13, 2014, DOI: http://dx.doi.org/10.1016/j.stem.2014.10.019

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Researchers Use Human Stem Cells to Create Light-sensitive Retina in a Dish

Researchers Use Human Stem Cells to Create Light-sensitive Retina in a Dish

Tuesday, 10 June 2014

These are rod photoreceptors (in green) within a

"mini retina" derived from human iPS cells in the

lab. Credit: Image courtesy of Johns Hopkins

Medicine. 

Using a type of human stem cell, Johns Hopkins researchers say they have created a three-dimensional complement of human retinal tissue in the laboratory, which notably includes functioning photoreceptor cells capable of responding to light, the first step in the process of converting it into visual images.

"We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," says study leader M. Valeria Canto-Soler, Ph.D., an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

She says the work, reported online June 10 in the journal Nature Communications, "advances opportunities for vision-saving research and may ultimately lead to technologies that restore vision in people with retinal diseases."

Like many processes in the body, vision depends on many different types of cells working in concert, in this case to turn light into something that can be recognized by the brain as an image. Canto-Soler cautions that photoreceptors are only part of the story in the complex eye-brain process of vision, and her lab hasn't yet recreated all of the functions of the human eye and its links to the visual cortex of the brain.

"Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start," she says.

The achievement emerged from experiments with human induced pluripotent stem cells (iPS) and could, eventually, enable genetically engineered retinal cell transplants that halt or even reverse a patient's march toward blindness, the researchers say.

The iPS cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body. In this case, the Johns Hopkins team turned them into retinal progenitor cells destined to form light-sensitive retinal tissue that lines the back of the eye.

Using a simple, straightforward technique they developed to foster the growth of the retinal progenitors, Canto-Soler and her team saw retinal cells and then tissue grow in their petri dishes, says Xiufeng Zhong, Ph.D., a postdoctoral researcher in Canto-Soler's lab. The growth, she says, corresponded in timing and duration to retinal development in a human foetus in the womb. Moreover, the photoreceptors were mature enough to develop outer segments, a structure essential for photoreceptors to function.

Retinal tissue is complex, comprising seven major cell types, including six kinds of neurons, which are all organized into specific cell layers that absorb and process light, "see," and transmit those visual signals to the brain for interpretation. The lab-grown retinas recreate the three-dimensional architecture of the human retina.

"We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina," says Canto-Soler.

"But when we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do."

When the retinal tissue was at a stage equivalent to 28 weeks of development in the womb, with fairly mature photoreceptors, the researchers tested these mini-retinas to see if the photoreceptors could in fact sense and transform light into visual signals.

They did so by placing an electrode into a single photoreceptor cell and then giving a pulse of light to the cell, which reacted in a biochemical pattern similar to the behaviour of photoreceptors in people exposed to light.

Specifically, she says, the lab-grown photoreceptors responded to light the way retinal rods do. Human retinas contain two major photoreceptor cell types called rods and cones. The vast majority of photoreceptors in humans are rods, which enable vision in low light. The retinas grown by the Johns Hopkins team were also dominated by rods.

Canto-Soler says that the newly developed system gives them the ability to generate hundreds of mini-retinas at a time directly from a person affected by a particular retinal disease such as retinitis pigmentosa. This provides a unique biological system to study the cause of retinal diseases directly in human tissue, instead of relying on animal models.

The system, she says, also opens an array of possibilities for personalized medicine such as testing drugs to treat these diseases in a patient-specific way. In the long term, the potential is also there to replace diseased or dead retinal tissue with lab-grown material to restore vision.

Source: Johns Hopkins Medicine 

Contact: Lauren Nelson

Reference:

Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs

Xiufeng Zhong, Christian Gutierrez, Tian Xue, Christopher Hampton, M. Natalia Vergara, Li-Hui Cao, Ann Peters, Tea Soon Park, Elias T. Zambidis, Jason S. Meyer, David M. Gamm, King-Wai Yau, M. Valeria Canto-Soler

Nature Communications 5, 4047, doi:10.1038/ncomms5047

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Stem Cell Research Could Expand Clinical Use of Regenerative Human Cells

Stem Cell Research Could Expand Clinical Use of Regenerative Human Cells

Tuesday, 19 March 2013

Research led by a biology professor in the School of Science at Indiana University-Purdue University Indianapolis (IUPUI) has uncovered a method to produce retinal cells from regenerative human stem cells without the use of animal products, proteins or other foreign substances, which historically have limited the application of stem cells to treat disease and other human developmental disorders.

The study of human induced pluripotent stem cells (hiPSCs) has been pursued vigorously since they were first discovered in 2007 due to their ability to be manipulated into specific cell types. Scientists believe these cells hold considerable potential for cell replacement, disease modelling and pharmacological testing. However, clinical applications have been hindered by the fact that, to date, the cells have required animal products and proteins to grow and differentiate.

Jason Meyer, Ph.D., assistant professor of

biology, has produced retinal cells from human

induced pluripotent stem cells without the use

of any animal products or foreign substances.

The chemical method could help expand clinical

 use of stem cell regeneration. Credit: School

of Science at IUPUI. 

A research team led by Jason S. Meyer, Ph.D., assistant professor of biology, successfully differentiated hiPSCs in a lab environment — completely through chemical methods — to form neural retinal cell types (including photoreceptors and retinal ganglion cells). Tests have shown the cells function and grow just as efficiently as those cells produced through traditional methods.

"Not only were we able to develop these (hiPSC) cells into retinal cells, but we were able to do so in a system devoid of any animal cells and proteins," Meyer said.

"Since these kinds of stem cells can be generated from a patient's own cells, there will be nothing the body will recognize as foreign."

In addition, this research should allow scientists to better reproduce these cells because they know exactly what components were included to spur growth and minimize or eliminate any variations, Meyer said. Furthermore, the cells function in a very similar fashion to human embryonic stem cells, but without controversial or immune rejection issues because they are derived from individual patients.

Retinal pigment epithelial (RPE) cells derived

from human induced pluripotent stem cells

possess numerous characteristics of native

RPE cells when examined by immunocyto-

chemistry. Credit: Jason Meyer. 

"This method could have a considerable impact on the treatment of retinal diseases such as age-related macular degeneration and forms of blindness with hereditary factors," Meyer said.

"We hope this will help us understand what goes wrong when diseases arise and that we can use this method as platform for the development of new treatments or drug therapies."

"We're talking about bringing stem cells a significant step closer to clinical use," Meyer added.

Meyer, along with two graduate students, have worked for two years on this research with the help of an Indiana University Collaborative Research Grant and funding from the School of Science at IUPUI and the American Health Assistance Foundation.

The research will be published in the April edition of Stem Cells Translational Medicine. Co-authors include Akshayalakshmi Sridhar and Melissa M. Steward.

Meyer began researching hiPSCs while he was a post-doctoral research associate at the University of Wisconsin in Madison, where James Thomson, Ph.D., was one of two investigators to develop hiPSCs from adult cells in 2007. The other, Shinya Yamanaka, Ph.D, from Japan's Kyoto University, was awarded the Nobel Prize for Physiology or Medicine in 2012 for discovering the ability of mature cells to be reprogrammed into stem cells.

Source: Indiana University-Purdue University Indianapolis School of Science 

Contact: David Hosick

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Scientists See New Hope for Restoring Vision with Stem Cell Help

Scientists See New Hope for Restoring Vision with Stem Cell Help

Wednesday, 13 June 2012

This is a human ES cell-derived optic cup 

generated in our self-organization culture 

(culture day 26). Bright green, neural retina; 

off green, pigment epithelium; blue, nuclei; 

red, active myosin (strong in the inner surface 

of pigment epithelium). Credit: Nakano 

et al. Cell Stem Cell Volume 10 Issue 6. 

Human-derived stem cells can spontaneously form the tissue that develops into the part of the eye that allows us to see, according to a study published by Cell Press in the 5th anniversary issue of the journal Cell Stem Cell. Transplantation of this 3D tissue in the future could help patients with visual impairments see clearly.

"This is an important milestone for a new generation of regenerative medicine," says senior study author Yoshiki Sasai of the RIKEN Center for Developmental Biology.

"Our approach opens a new avenue to the use of human stem cell-derived complex tissues for therapy, as well as for other medical studies related to pathogenesis and drug discovery."

During development, light-sensitive tissue lining the back of the eye, called the retina, forms from a structure known as the optic cup. In the new study, this structure spontaneously emerged from human embryonic stem cells (hESCs) — cells derived from human embryos that are capable of developing into a variety of tissues — thanks to the cell culture methods optimized by Sasai and his team.

The hESC-derived cells formed the correct 3D shape and the two layers of the optic cup, including a layer containing a large number of light-responsive cells called photoreceptors. Because retinal degeneration primarily results from damage to these cells, the hESC-derived tissue could be ideal transplantation material.

Beyond the clinical implications, the study will likely accelerate the acquisition of knowledge in the field of developmental biology. For instance, the hESC-derived optic cup is much larger than the optic cup that Sasai and collaborators previously derived from mouse embryonic stem cells, suggesting that these cells contain innate species-specific instructions for building this eye structure.

"This study opens the door to understanding human-specific aspects of eye development that researchers were not able to investigate before," Sasai says.

The anniversary issue containing Sasai's study will be given to each delegate attending the 2012 ISSCR meeting in Yokohama, Japan. To highlight the ISSCR meeting and showcase the strong advances made by Japanese scientists in the stem cell field, the issue will also feature two other papers from Japanese authors, including the research groups of Akira Onishi and Jun Yamashita. In addition, the issue contains a series of reviews and perspectives from worldwide leaders in stem cell research.

Source: Cell Press 

Contact: Lisa Lyons

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Origin of Cells Associated with Nerve Repair Discovered

Findings could one day lead to improved treatment of spinal cord injuries
Tuesday, 16 November 2010

Scientists have discovered the origin of a unique type of cell known for its ability to support regeneration in the central nervous system. Their findings, published this week in the journal Proceedings of the National Academy of Sciences USA (PNAS), raise the possibility of obtaining a more reliable source of these cells for use in cell transplantation therapy for spinal cord injuries.

Olfactory Nerve. The origin of cells

associated with nerve repair has been

discovered. The findings could one

day lead to improved treatment of

spinal cord injuries.

Credit: Dr. Perrine Barraud.

Olfactory ensheathing cells (OECs), as the name suggests, ensheath and protect the nerve fibres in the olfactory nerve, which transmit olfactory (smell) information to the brain from receptor cells sitting in the lining of the nose. Excitingly, OECs can promote nerve repair when transplanted into the damaged spinal cord. They can also be grown in dishes from pieces of nasal lining but, unfortunately, in such small quantities that this may not be a viable option for use in treatments.

Dr Clare Baker, from the Department of Physiology, Development and Neuroscience at the University of Cambridge, lead author of the study, said: "In theory, one should be able to purify OECs from a patient's nose and transplant them into the damaged spinal cord to promote nerve repair, without any fear of graft rejection.”

"Unfortunately, there aren't very many OECs in the nasal lining, and this tissue also contains other peripheral nerve fibres, ensheathed by cells that look very similar to OECs but which are less effective at promoting spinal cord repair. As a result, it has thus far proven difficult to purify sufficiently large numbers of OECs from the nasal lining for effective use in cell transplantation therapy."

For the last 25 years, OECs have been thought to be formed by the nasal lining itself. The new research, however, reveals a different origin for OECs that may enable scientists in the future to produce them in large quantities from adult stem cells.

The researchers, funded by the Wellcome Trust and the Isaac Newton Trust, have discovered that, like all other cells ensheathing peripheral nerve fibres, OECs are actually derived from a group of embryonic stem cells called "neural crest cells". Neural crest stem cells persist in adult skin and hair follicles, and other researchers have already shown that it is possible to isolate these stem cells and grow them in the lab.

"The next step is to work out how to turn these stem cells into OECs. To do this, we need to investigate how this process happens normally in the developing embryo," Dr Baker said.


Cross-section of the embryonic chicken

olfactory bulb showing neural

crest-derived olfactory ensheathing

cells (green). (Blue, axons; red,

low-affinity neurotrophin receptor.)

Credit: Dr. Perrine Barraud.

 "It is important to note that it will take many years for our research to have any impact on therapy for people with damaged spinal cords. However, we are hopeful that our discovery provides a fresh starting point for new research into ways of purifying large numbers of these cells for use in treatments," Dr Baker continued.

In order to determine the origin of OECs, the scientists tagged embryonic neural crest cells with 'green fluorescent protein' (GFP), so that only neural crest cells and their descendants glowed green under ultraviolet light. They did this in chicken embryos by transplanting GFP-labelled neural crest cells into unlabelled host embryos; they also looked at mouse embryos in which, through a genetic trick, the only cells that expressed GFP were neural crest cells.

They were then able to follow what happened to neural crest cells and their descendants as the olfactory nerve developed. By analysing thin sections of these embryos under the microscope, they were able to see that lots of green neural crest-derived cells were associated with the developing olfactory nerve fibres. These green cells expressed molecular markers characteristic of OECs, and crucially, they ensheathed bundles of the olfactory nerve fibres, i.e., they were indeed olfactory ensheathing cells.

Source: University of Cambridge
Contact: Contact: Genevieve Maul

Reference:
Neural crest origin of olfactory ensheathing glia
Perrine Barraud, Anastasia A. Seferiadis, Luke D. Tyson, Maarten F. Zwart, Heather L. Szabo-Rogers, Christiana Ruhrberg, Karen J. Liu, and Clare V. H. Baker
PNAS, 15 November 2010, doi:10.1073/pnas.1012248107
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Researchers Create Retina from Human Embryonic Stem Cells

Complex tissue structure offers hope to millions with degenerative eye disorders
Thursday, 27 May 2010

UC Irvine scientists have created an eight-layer, early-stage retina from human embryonic stem cells, the first three-dimensional tissue structure to be made from stem cells.

It also marks the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions.

"We made a complex structure consisting of many cell types," said study leader Hans Keirstead of the Reeve-Irvine Research Center and the Sue and Bill Gross Stem Cell Research Center at UCI.

"This is a major advance in our quest to treat retinal disease."

In previous studies on spinal cord injury, the Keirstead group originated a method by which human embryonic stem cells could be directed to become specific cell types, a process called differentiation. Results of those studies are leading to the world's first clinical trial using a stem cell-based therapy for acute spinal cord injury.

In this study, the Keirstead team utilized the differentiation technique to create the multiple cell types necessary for the retina. The greatest challenge, Keirstead said, was in the engineering. To mimic early-stage retinal development, the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths.

"Creating this complex tissue is a first for the stem cell field," Keirstead said.

"Dr. Gabriel Nistor in our group addressed a really interesting scientific problem with an engineering solution, showing that gradients of solutions can create complex stem cell-based tissues."

The retina is the inside back layer of the eye that records the images a person sees and sends them via the optic nerve from the eye to the brain. Retinal diseases are particularly damaging to sight. More than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood.

"What's so exciting with our discovery is that creating transplantable retinas from stem cells could help millions of people, and we are well on the way," Keirstead said.

The UCI researchers are testing the early-stage retinas in animal models to learn how much they improve vision. Positive results would lead to human clinical trials.
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Successful Stem Cell Therapy for Treatment of Eye Disease

Successful Stem Cell Therapy for Treatment of Eye Disease Monday, 21 December 2009 Newly published research, by investigators, at the North East England Stem Cell Institute (NESCI) in the journal Stem Cells reported the first successful treatment of eight patients with "Limbal Stem Cell Deficiency" (LSCD) using the patients' own stem cells without the need of suppressing their immunity. LSCD is a painful, blinding disease that requires long-term, costly treatment with frequent clinic visits and intensive hospital admissions. The vision loss due to LSCD makes this disease not only costly, but often requires social support due to the enormous impact on patient's quality of life. This is further magnified by the fact that LSCD mostly affects young patients. Dr Francisco Figueiredo, a member of the NESCI team, said: "Corneal cloudiness has been estimated to cause blindness in 8 million people (10% of total blindness) worldwide each year. A large number of ocular surface diseases, both acquired and congenital, share features of partial or complete LSCD. " Chemical burns to the eye are the most common cause of LSCD. Professor Lako said: "This study demonstrates that transplantation of cultured corneal stem cells without the use of animal cells or products is a safe and effective method of reconstructing the corneal surface and restoring useful sight in patients with unilateral LSCD.” "This research shows promise to help hundreds of people regain their sight. These exciting results offer a new treatment and hope for people with LSCD." Professor Michael Whitaker FMedSci, Co-Director of NESCI, which is a collaboration between Durham and Newcastle Universities, Newcastle NHS Foundation Trust and other partners, said: "Stem cells from bone marrow have been used successfully for many years to treat cancer and immune disease, but this is the first successful stem cell therapy using stem cells from the eye without animal products to treat disease, an important step towards the clinic. Because the early results look so promising, we are thinking hard now about how to bring this treatment rapidly into the clinic as we complete the necessary clinical trials, so that the treatment can be shared with all patients that might benefit." "The Newcastle team has obtained some very impressive results in patients following stem cell transplants to repair the surface of the cornea. It is hugely exciting to see that a type of stem cell therapy can now be applied routinely to treat a form of blindness," said Professor Robin Ali, FMedSci, Department of Genetics, UCL Institute of Ophthalmology, London. "These results also provide us with further encouragement to develop stem cell therapies to repair the retina in order to treat conditions such as age related macular degeneration." A larger study involving 24 new patients is currently underway with funding from the UK's Medical Research Council. ......... ZenMaster

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