—Stem cell therapy
is in its infancy, and the first steps have been taken to address atrophic age-related macular degeneration
(AMD) with some success among several interesting treatment strategies
, according to Allen C. Ho, MD.
“It is an exciting time for cell therapy, and currently there are more than 12 groups around the world that are problem-solving scientific questions and refining surgical techniques for treating dry AMD, the potential for stem cell, and other cell therapies for atrophic AMD,” said Dr. Ho, director of retina research, Mid Atlantic Retina and Wills Eye Hospital, and professor of ophthalmology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.
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While the progress in stem cell therapy generally has been “halting,” in Ophthalmology, progress is being made, especially in retina, Dr. Ho noted.
This progress is typically seen in partnership with industry.
The primary question in stem cell research is whether cells that are from embryonic or adult sources when placed in atrophic areas can support or replace tissue and function in atrophic AMD.
Three cell types are being evaluated in cell therapy trials to treat atrophic AMD:
· Stem cells, which are defined as having the properties of pluripotential differentiation and self-renewal
· Stem cell-derived but differentiated cells, such as stem cell-derived retinal pigment epithelial (RPE) cells
· Adult non-stem cell therapies derived from the umbilical cord
Next: Approaches to stem cell therapy
There are two approaches to stem cell therapy, the first being replacement, in which the cells are isolated from the source, the cells are expanded and differentiated, and the cells are then placed near the atrophic areas in an attempt to reproduce function.
A number of companies are engaged in this approach and a few companies—e.g., Regenerative Patch Technology—are using embryonic-derived but differentiated stem cells into RPE cells. Dainippon Sumitomo Pharma is working with an induced-pluripotential stem cell, according to Dr. Ho.
The second approach to stem cell therapy is the trophic approach, which may be the simpler of the two, he explained. In this approach, cells are harvested and expanded but not differentiated. The cells then are placed next to areas of atrophy in an attempt to support those tissues by either local cytokines or cell-to-cell interaction, he explained.
Janssen Research and Development is involved in this approach. The Neurotech investigators use a genetically transfected cell line to elute trophic factors into the vitreous from an intravitreal implant, Dr. Ho reported.
However, he pointed out that a good model for atrophic AMD is not available, and the preclinical proof of concept for several cell lines is in the Royal College of Surgeons rat. In this approach, the cells are placed in the subretinal space and have shown preservation of retinal tissue and improved visual function in the rat pups, he recounted.
Next: Cell delivery strategies
“Multiple delivery strategies are being evaluated that include injections of cells transvitreally, ab externo into the subretinal space, and cells placed on sheets,” he said. “The last is being done by Regenerative Patch Technology, using a sheet of embryonic-derived, but differentiated stem cells into RPE cells are placed on a parylene synthetic Bruch’s membrane.”
When the patch of stem cells was in place in pigs, no rejection was seen and the RPE showed good survival.
He also reported that after injection of embryonic-derived human RPE cells in a phase I/II study, progressive pigmentation was observed at the border of the geographic atrophy, which may represent functional RPR cells.
Another example was from the Janssen study in which adult umbilical cells were used. Six months after cellular placement adjacent to an area of atrophy, the patient had improved vision from 20/800 to 20/200.
“This is an exciting time for cell therapy,” Dr. Ho said. “Multiple groups are in early clinical trials. All the cell lines investigated to date have been tolerated in the subretinal space. No immune rejection or tumor formation has occurred. Surgical delivery will be key. Refinement of these techniques is ongoing.
“There has been progress in this field, but there certainly are many unanswered questions,” he concluded.