Stem Cell Research Status, Tables, etc. courtesy of Irv Arons Journal:

Stem Cells in Opthalmology Primer, courtesy of Irv Arons Journal:

Stem Cell Clinical Trials for Retinopathies Clinical Trials Summary from Dr. Ian MacDonald 7-2-2013:
  • Technical Version:

  • Lay Version:

Stem cell replacement therapy - Dr. Chris Moen 5-18-2013:
Stem cells are progenitors of the specialized cells in our body and, with the appropriate stimulating factors, are capable of differentiating into a variety of cells. Common stem cells are derived from embryos, although access to these cells is limited by a variety of factors. More recent research has established a protocol to create induced pluripotent stem cells (iPS) from fibroblasts commonly found in our tissue. iPS cells are limited in their capacity in comparison to embryonic stem cells and previously could not produce a cell line that can perpetuate permanently. Researchers are now able to perpetuate iPS cell lines. The current protocols used to create iPS cells carry along a risk of tumor genesis by inadvertently turning on genes known as oncogenes as a result of the transformative process. More research is being performed to address this potentially serious issue limiting iPS cells’ use as human therapies. Stem cells are also readily available in human bone marrow which can be obtained via bone marrow biopsy. These stem cells can be directly applied to the patient from whom they were obtained without concern for rejection. From my research, the bone marrow stem cells (BMS) are mesenchymal, which are not as pluripotent as other stem cells and whose scope does not appear to include RPE and photoreceptor cells. However, preliminary data suggests that BMS cells may stabilize blood vessels and surrounding supportive tissue, thereby preventing further degeneration and promoting health to damaged or dying cells. I do not find evidence that these cells can actually replicate into photoreceptor or RPE cells, limiting their ability to truly replace lost vision.

Currently, the Choroideremia Research Foundation funds two separate stem cell projects. Dr. Viki Kalatzis is taking tissue from CHM patients, creating CHM-affected iPS cells, and planning to create CHM-affected RPE and photoreceptor cells for use in current and future research projects. Dr. Miguel Seabra is being funded to create mouse iPS cells, treat these cells with the gene therapy vector he has created (and is currently underway in human clinical trials), and attempt to create normal (non-CHM) RPE and/or photoreceptor cells. If successful, Dr. Seabra’s work would establish a protocol to perform similar experimentation in humans. The Choroideremia Research Foundation is funding this project.

Stem cell therapies are in varied stages of research and development, including studies for specific diseases currently undergoing human clinical trials. The following are current studies found on related to retinal degenerative diseases:
  • Stargardt’s Macular Dystrophy – embryonic cells, Phase I (Advanced Cell Technologies)
  • Retinitis Pigmentosa – bone marrow derived cells, Phase II (Sao Paulo)
  • Age-related Macular Degeneration – bone marrow derived cells, Phase I/II (Sao Paulo)
  • Retinopathy – bone marrow derived cells, Phase I (UC-Davis)
  • Age-related Macular Degeneration – human central nervous system cells, Phase I/!! (Stem Cells, Inc.)
  • Dry age-related Macular Degeneration – embryonic cells, Phase I/II (two studies, Pfizer and CHA Bio)
  • The CRF has been approached by Dr. Susanna Park for potential funding to include CHM patients in her clinical trial above using BMS cells for treatment of a variety of retinal dystrophies. Her subject base is wide in scope and includes retinal degenerative diseases such as CHM and RP as well as non-genetic disorders such as diabetic retinopathy.

Writeup on various stem cell therapies updated 6-14-2013:

Miscellaneous news items:

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina:
For the first time, scientists have successfully transplanted light-detecting cells in the retina, grown from embryonic stem cells, into mice--a feat that could advance similar therapies using the artificial cells to treat degenerative eye diseases toward human trials.The animal transplant is a huge step for embryonic stem cell-based therapies, which have moved slowly to the clinic despite their promise.

A team of scientists from University College London's Institute of Ophthalmology and Moorfields Eye Hospital in London grew a synthetic retina from embryonic stem cells in the lab, extracted the light-sensitive photoreceptor cells that line the back of the eyes, and transplanted the cells into night-blind mice. Researchers observed that the cells seemed to develop normally, integrating into the existing retina and forming the nerve connections needed to transmit visual information to the brain.

In degenerative eye diseases such as age-related macular degeneration, retinitis pigmentosa and diabetes-related blindness, the loss of photoreceptors causes vision to deteriorate and can lead to blindness. "This study is an important milestone on the road to developing a widely available cell therapy for blindness as it proves unequivocally that embryonic stem cells can provide a renewable source of photoreceptors that could be used in treatments," said Dr. Rob Buckle, head of Regenerative Medicine at the U.K.'s Medical Research Council, which funded the study. Previous research by the UCL and Moorfields Eye team found that transplanting immature rod cells--essential for seeing in the dark--from the retinas of healthy mice into blind mice can restore their sight. Since this approach would not be practical in humans, the investigators sought to grow retinas containing the various nerve cells needed for sight.

Using a new technique developed in Japan that involves 3D culture and differentiation of mouse embryonic stem cells, the researchers grew retinal precursor cells that closely resembled cells that developed normally. They then injected about 200,000 artificially grown cells into the retinas of the night-blind mice. Three weeks after the transplant, the artificial cells integrated into the mouse retinas and showed signs of looking like normal mature rod cells. After 6 weeks, the cells were still present, and researchers observed synapse formation, suggesting that the new cells were able to connect with the existing retinal circuitry. The study appears in Nature Biotechnology.

Human embryonic stem cells, or hESCs, are thought to have greater potential for treating disease because of their ability to turn, or differentiate, into more types of human cells than adult stem cells can, yet there are no FDA-approved treatments that use them. The major concern with transplanting hESCs into patients is the potential for hESCs to grow tumors, including teratoma--tumorlike formations containing tissues belonging to all three germ layers.

- here's the Nature Biotechnology abstract
- read the press release
Related Articles:

Read more: First successful transplant of retinas made from embryonic stem cells - FierceBiotech

Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs - Zhong X, Gutierrez C, Xue T, Hampton C, Vergara MN, Cao LH, Peters A, Park TS, Zambidis ET, Meyer JS, Gamm DM, Yau KW7, Canto-Soler MV -Nat Commun. 2014 Jun 10;5:4047. doi: 10.1038/ncomms5047:

Gene Therapy Might Grow Replacement Tissue Inside the Body - Co investigated by Charles Gersbach

PubMed link:

By combining a synthetic scaffolding material with gene delivery techniques, researchers at Duke University are getting closer to being able to generate replacement cartilage where it’s needed in the body. Performing tissue repair with stem cells typically requires applying copious amounts of growth factor proteins—a task that is very expensive and becomes challenging once the developing material is implanted within a body. In a new study, however, Duke researchers found a way around this limitation by genetically altering the stem cells to make the necessary growth factors all on their own.

They incorporated viruses used to deliver gene therapy to the stem cells into a synthetic material that serves as a template for tissue growth. The resulting material is like a computer; the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue. The study appears online the week of Feb. 17 in the Proceedings of the National Academy of Sciences.

Farshid Guilak, director of orthopaedic research at Duke University Medical Center, has spent years developing biodegradable synthetic scaffolding that mimics the mechanical properties of cartilage. One challenge he and all biomedical researchers face is getting stem cells to form cartilage within and around the scaffolding, especially after it is implanted into a living being. The traditional approach has been to introduce growth factor proteins, which signal the stem cells to differentiate into cartilage. Once the process is under way, the growing cartilage can be implanted where needed. “But a major limitation in engineering tissue replacements has been the difficulty in delivering growth factors to the stem cells once they are implanted in the body,” said Guilak, who is also a professor in Duke’s Department of Biomedical Engineering. “There’s a limited amount of growth factor that you can put into the scaffolding, and once it’s released, it’s all gone. We need a method for long-term delivery of growth factors, and that’s where the gene therapy comes in.

For ideas on how to solve this problem, Guilak turned to his colleague Charles Gersbach, an assistant professor of biomedical engineering and an expert in gene therapy. Gersbach proposed introducing new genes into the stem cells so that they produce the necessary growth factors themselves. But the conventional methods for gene therapy are complex and difficult to translate into a strategy that would be feasible as a commercial product.

This type of gene therapy generally requires gathering stem cells, modifying them with a virus that transfers the new genes, culturing the resulting genetically altered stem cells until they reach a critical mass, applying them to the synthetic cartilage scaffolding and, finally, implanting it into the body. “There are a few challenges with that process, one of them being that there are way too many extra steps,” said Gersbach. “So we turned to a technique I had previously developed that affixes the viruses that deliver the new genes onto a material’s surface.”

The new study uses Gersbach’s technique—dubbed biomaterial-mediated gene delivery—to induce the stem cells placed on Guilak’s synthetic cartilage scaffolding to produce growth factor proteins. The results show that the technique works and that the resulting composite material is at least as good biochemically and biomechanically as if the growth factors were introduced in the laboratory. “We want the new cartilage to form in and around the synthetic scaffold at a rate that can match or exceed the scaffold’s degradation,” said Jonathan Brunger, a graduate student who has spent time in both Guilak’s and Gersbach’s laboratories developing and testing the new technique. “So while the stem cells are making new tissue (in the body), the scaffold can withstand the load of the joint. In the ideal case, one would eventually end up with a viable cartilage tissue substitute replacing the synthetic material.”

While this study focuses on cartilage regeneration, Guilak and Gersbach say that the technique could be applied to many kinds of tissues, especially orthopaedic tissues such as tendons, ligaments and bones. And because the platform comes ready to use with any stem cell, it presents an important step toward commercialization. “One of the advantages of our method is getting rid of the growth factor delivery, which is expensive and unstable, and replacing it with scaffolding functionalized with the viral gene carrier,” said Gersbach. “The virus-laden scaffolding could be mass-produced and just sitting in a clinic ready to go. We hope this gets us one step closer to a translatable product.”

This work was supported in part by the Nancy Taylor Foundation for Chronic Diseases, the Arthritis Foundation, the AO Foundation, the National Science Foundation (CAREER Award CBET-1151035) and the National Institutes of Health (AR061042, AR50245, AR48852, AG15768, AR48182, AG46927 and OD008586). Read more at

Stem cells hold promise for restoring, replacing RPE, RGCs 10-24-2013:
SEATTLE – In the field of posterior segment disease, stem cells can be used to motivate endogenous repair or keep what you have left healthy and surviving, according to Jeffrey Goldberg, MD, PhD, here at the American Academy of Optometry’s plenary session.

He said a number of unmet needs exist in glaucoma: “better IOP-lowering approaches, treatments beyond reducing pressure, saving cells that haven’t died yet, replacing cells that have died (through stem cell therapy) and neuroenhancement (taking the dysfunctional cells and giving them a booster shot to enhance their function, thereby restoring visual function).
“We can inject almost any donor cells into the eye as long as they will secrete these growth factors and keep alive whatever we have left,” he said.

Stem cells are looked upon for taking over the function of the retinal pigment epithelium (RPE) at the back of the eye, Goldberg said, but the process is not as easy for retinal ganglion cell (RGC) therapy. “We’re focusing on the inner portion of the retina, where we’re trying to get RGC transplants to replace the function of the RGC,” he said. “If we took stem cells out of the equation and skipped the problem of getting a stem cell to turn into a RGC, what if we take an actual RGC and transplant it into the retina? We do these cell transplants, and initially after an intravitreal injection, we see the cells layer over the surface. But if we give them some time, some of the cells actually do migrate into the ganglion cell layer where they’re supposed to live. These transplanted cells extend the neurites; they do some of the things they’re supposed to do.”

Goldberg said he has studied survival, migration and neurite growth. “In almost all metrics, the stem cell-derived RGCs did almost as well as the transplanted RGCs,” he said. “We are interested in not just whether they look like they’re going to the right place, but how they’re performing,” he continued. “Primary RGCs were able to receive about twice as many synapses as the stem cell-derived RGCs. These stem-cell derived RGCs are not fully functional. This raises questions. How do we tell a stem cell to be a functionally better RGC?”

Goldberg said progress is being made in the area of turning stem cells into ganglion cells. He said it is not possible to use embryonic human tissue for this purpose, but induced fluripotent stem cells from the skin may be differentiated into retinal progenitor-type cells. “If we overexpressed the certain transcription factors we need, can we get them to turn into RGCs?” he asked. “Ciliary margin cells are generating photoreceptors from RGC, amacrine cells and glia in culture.

“We may be able to replace the whole retina at some point,” Goldberg continued. “This approach could yield therapeutic value in the end.”
The plenary session was partially sponsored by Primary Care Optometry News.

A new way to create primitive stem cells 9/19/2013: "We uncovered a new major pathway that prevents skin cells from converting back to an embryonic state," said senior researcher Dr Jacob Hanna, of the Weizmann Institute of Science in Rehovot, Israel. "If we block this pathway, we increase current methods of making iPS cells up to 100% (efficiency), and eliminate the randomness and protracted nature of the process," he added.

Stem cells have been a hot topic in scientific research for years, with controversy swirling around the study of embryonic stem cells – because that requires an embryo to be destroyed in the process. But in 2007, researchers had their first success with reprogramming adult human cells to become embryonic-like stem cells. It's done by activating just a few key genes that override the identity of an adult cell and send it back to an embryonic-like state. But the process has been hampered by inefficiency, and, Hochedlinger said, "We didn't know why that was." The new findings point the finger at a molecule called Mbd3. Hanna's team found that blocking its action allowed human skin cells to be transformed into iPS cells almost 100% of the time.

Stem cells generated from in vivo reprogramming 9/18/2013 - Spanish scientists have generated stem cells from mature mouse cells. Nothing new there. Shinya Yamanaka did that 9 years ago. But the difference between this and Yamanaka’s work – and every other bit of stem cell research up until now – is that the stem cells in Madrid were not generated in a petri dish but in a living mouse. The researchers, reporting in Nature, found that they could reprogram induced pluripotent stem (iPS) cells in vivo from mature mouse cells. “You don’t need the milieu of the petri dish,” George Daley, director of stem cell transplantation at Boston Children’s Hospital, who was not involved with the work, told Bloomberg. “You can just do this right in the tissues. That’s surprising.”

The team at the Spanish National Cancer Research Centre in Madrid genetically engineered mice to express four genes – Oct4, Sox2, Klf4 and c-Myc – to create iPS cells. The researchers found that multiple teratomas emerged from organs within the mice, indicative of cellular reprogramming. Analysis of the iPS cells revealed that they more closely resemble embyronic stem cells than in vitro iPS cells.
Because of the formation of teratomas, the work remains more of an exciting proof-of-concept rather than immediate therapeutic application, but the research does open up a new avenue for stem cell research.
“This opens up new possibilities in regenerative medicine,” said team leader Manuel Serrano. According to the Nature news article, Serrano’s team is now going to look at how tumour formation can be avoided, and whether the reprogrammed cells can regenerate specific cell types in a controlled manner. PubMed link:

Japan approves stem cell clinical trials 7/19/2013 - TOKYO: Japan's government on Friday gave its seal of approval to the world's first clinical trials using stem cells harvested from a patient's own body. Health Minister Norihisa Tamura signed off on a proposal by two research institutes that will allow them to begin tests aimed at treating age-related macular degeneration (AMD), a common medical condition that causes blindness in older people, using “induced Pluripotent Stem (iPS) cells”:

Brief Report: Self-Organizing Neuroepithelium from Human Pluripotent Stem Cells Facilitates Derivation of Photoreceptors 7/21/2013:

New method to produce blood cells from stem cells could yield a purer, safer cell therapy, STEM CELLS Translational Medicine, 7/15/2013:
Durham, NC - A new protocol for reprogramming induced pluripotent stem cells (iPSCs) into mature blood cells, using just a small amount of the patient's own blood and a readily available cell type, is reported on in the current issue of STEM CELLS Translational Medicine. This novel method skips the generally accepted process of mixing iPSCs with either mouse or human stromal cells during the differentiation process and, in essence, ensures no outside and potentially harmful DNA is introduced into the reprogrammed cells. As such, it could lead to a purer, safer therapeutic grade of stem cells for use in regenerative medicine:,-safer-cell-therapy.aspx

Babraham Scientists make Stem Cell Discovery 7-11-2013:
Reported this week in the journal Cell Stem Cell, this new understanding of how epigenetic memory can be completely erased may prove useful in generating better quality cells for transplantation and cell-therapy purposes:

Mapping a route to stem cell therapies - iPS using transcription factors instead of gene therapy for iPS production 7-13-2013:

Japan Gives Approval For First Clinical Study To Cure A Form Of Blindness Using Stem Cells Made From Human Skin 6-26-2013:

The Future Of Cell Reprogramming: Some Experts Weigh In 6-20-2013:

Health care innovations: good therapy for Ohio and beyond 6-20-2013:

Have Scientists Finally Found Truly Pluripotent Adult Stem Cells? 6-8-2013:

New research could pave the way to generate these stem cells efficiently to better understand and develop treatments for diseases such as multiple sclerosis, Parkinson's disease and muscular degeneration:

Vascular stem cell derived structures:

There is a need to treat the damage to the choroid retinal layer in choroideremia, gyrate atrophy, atrophic AMD (dry), diabetic retinopathy and other eye disorders in which the retinal vascular layers are affected:

Johns Hopkins Stem Cell-based Blood Vessels Function in Mice and Oxford Vessel work:

Oxford blood vessel work:

Establishment of Human Retinal Microvascular Endothelial Cells with Extended Life-span

The role of K+ and Cl- channels in the regulation of retinal arteriolar tone and blood flow - Needham etal - Investigative Ophthalmology & Visual Science, 03/19/2014:

Blood vessel cells can repair, regenerate organs, say Weill Cornell scientists 11-27-2013:

3D bioprinting:

Transdifferentiation - Cell type to cell type without reprogramming to stem cell state:


ESC and cell transplantation - Professor Robin Ali at the University College of London is working on using embryonic stem cells for transplantation.

iPS creation - Kang Zhang, MD PhD at the University of California, San Diego is working to establish 600 plus cell lines modeling retinal degenerations with funding from CIRM (California Institute for Regenerative Medicine). These cell lines will be made available for other researchers.

iPS & retinal cell creation, replacement therapies - David M. Gamm, MD PhD at the University of Wisconsin is working on transplantation approach generating multilayer retinal RPE and PR scaffolded structures using iPS generated cells.

iPS & retinal cell creation, autologous replacement therapies - Dr. Budd Tucker, PhD at the University of Iowa, and his lab are focused on combining state-of-the-art patient-specific stem cell and biodegradable tissue engineering technologies to develop outer retinal equivalents, de novo, to be used as a means of retinal regeneration following transplantation.

Cell transplantation and regeneration, gene therapy - Stephen H. Tsang, MD PhD at Columbia University is working studying adult stem cells that reside in the retina and exploring ways to activate those for retinal regeneration in addition to his gene therapy work.

hES and hFT cell generation and transplantation - Michael J. Young, MD PhD at Schepen's Eye Institute - Masachusetts Eye & Ear is working on transplantation approach generating multilayer retinal RPE and PR scaffolded structures using hES and hFT generated cells.

CHM mouse CHM autologous stem cell pre-clinical work - Miguel Seabra, MD PhD at Imperial College is working on a transplant approach using cells from the transplant donor/ recipient that are genetically corrected, grown into retinal cells and then transplanted back into the donor/recipient.

Autologous bone marrow intravitreal stem cell transplantation - Susannah H. Park, MD PhD at University of California Davis is conducting human trials using her approach for Dry Age-related Macular Degeneration, Diabetic Retinopathy, Retina Vein Occlusion and Retinitis Pigmentosa.

Companies involved in stem cell technologies:

Advanced Cell Technologies, Inc., ACTC, is a public company is currently in Phase I/II trials using hESC to generate mature RPE cells that are delivered in suspension (with no scaffold for cell organization) via subretinal injection. Phase II trials are underway for dry AMD and Stargardt’s macular dystrophy. Safety phase has been successfully completed. Ability of the cells introduced in suspension to survive and integrate into the human retina and their efficacy are as yet unknown.

Regenerative Patch Technologies, Inc. is a private company working on a patch consisting of RPE cells oriented on an engineered scaffold primarily for dry AMD and Stargardts. The company expects to begin human trials in 2014 and has said they will consider other rare disease that are appropriate for their technologies. Most CHM researchers believe that a 2 layer RPE+PR approach would be more appropriate for CHM.

Stem Cells, Inc., STEM, is a public company that is developing treatments for spinal cord injury, retinal disease (AMD), and other degenerative disorders using human neural stem cells aka huCNS-SC. Michael Young with Harvard is a consultant and researcher affiliated with Reneuron.

Reneuron, Inc., RENE.L, is a public company developing treatments for stroke, retinitis pigmentosa and other neruological disorders using human embryonic stem cells aka hESC.

Miscellaneous Publications: