Recently I was at the World Alliance Forum in San Francisco (WAFSF), a great meeting on stem cells and regenerative medicine. WAFSF had some excellent talks and I saw one session on the use of stem cells to treat vision impairment that was particularly striking.
This session’s all-star lineup included Drs. David Hinton, Ann Tsukamoto, Henry Klassen, and Masayo Takahashi. I’m going to summarize the talks below with permission of all speakers. Note that these summaries are based on rapidly scrawled notes. Together these talks show just how far the translational stem cell vision field has come in the last few years and the very real promise for the coming years in this area for major clinical impact.
The session began with Hinton (pictured at left in USC photo) from the Project to Cure Blindness at USC, who spoke about research on treating geographic atrophy using retinal pigmented epithelial cells (RPEs). Hinton’s stem cell device is a polarized RPE monolayer. The team places 100,000 RPEs made from human embryonic stem cells (hESC) on a parylene membrane. My impression was that they are using H9 hESC for the preclinical studies, but I’m not 100% sure.
He indicated that because of the membrane there is no significant cellular migration, but there is PEDF and VEGF secretion and the RPEs appear resistant to stress. Are the RPEs functional? It seems so as there is rhodopsin phagocytosis.
For the studies he discussed, they used the RCS rat model of retinal degeneration of which there was a partial rescue by hESC-RPEs and encouragingly from a safety perspective, no teratomas.
Surprisingly, control parylene alone without cells has some rescue function, but with RPE there was substantially better organization and electrical function. One kind of cool thing from a techno perspective is that they invented a special delivery tool that gently folds the RPE sheet for insertion into the eye upon which it unfolds. It looked like it worked like a charm based on a video shown.
The next talk was from Ann Tsukamoto of StemCells, Inc.
They are studying the use of human CNS stem cells for treating dry eye AMD. These cells are called HuCNS-SC. After transplantation in mice the cells engraft and migrate. In RCS rats there is loss of RPEs and then 2ndary loss of photo receptors. HuCNS-SC transplanted at P21 migrate well (there’s no matrix). With transplant of HuCNS-SC they see maintenance of photoreceptors and visual acuity. What is the mechanism?
The final speaker of the session was Stem Cell Person of the Year, Masayo Takahashi, from RIKEN. She spoke about using RPEs made from human induced pluripotent stem cells (IPSC). She discussed treating wet AMD with the RPEs. I understood that to make IPSC they used the episomal vector approach.
They started with 24 IPSC lines, then picked the top 6 and then 3 of those lines were used to make the RPEs using a 4-month differentiation period. Of the original 6, it was notable that despite using an episomal vector, in one there was a plasmid remnant. So for all you folks out there using “transient”, “non-genetic” methods, one lesson here is to be sure to do the needed testing and validation of human IPSC lines.
They then pick pigmented clones and made sheets. It’s a lengthy and expensive process with one of the biggest expenses being the facility itself, which costs ~$500K/year just to run.
For safety testing and validation, they did their Lin28 PCR assay for residual IPSC as well as whole genome sequencing. In addition, no tumors were observed.
The RPE product, a 1.3 x 3 mm wide device, was just transplanted recently into the first human AMD patient. I think everyone is on the edge of their seat in this field to see how this clinical study progresses.
Looking to the future, Takahashi mentioned that allogeneic transplantation is an option and teams are moving in that direction. An IPSC cell bank with a variety of HLA types could be helpful to many patients in an allogeneic manner.
She also discussed the regulatory situation in Japan including the novel concept of adaptive licensing (see below the overview of the current regulatory system in Japan).
She mentioned that it is a fast system, but acknowledged that it has risks too. She also said they are planning photoreceptor transplantation in 5 years for RP.
Overall these four talks were very encouraging for the future of treating various forms of vision impairment using stem cells.