Transplants Derived From Human Stem Cells Help Restore Vision In Rats With Retinal Disease

In a series of several experiments, researchers generated RPE cells from 18 different hES cell lines. Cells derived from one of the NIH-approved cell lines were injected into RCS rats in an attempt to compensate for the photoreceptor cell loss caused by a genetic trait carried by such RCS rats. These animals lose their photoreceptor cells over several months following birth and are used to study conditions under which this loss, similar to that occurring in macular degeneration, can be prevented or treated.

In the study published in Cloning and Stem Cells, rats were injected with hES- derived RPE cells into the subretinal space of the eye at 21 days after their birth, an age at which photoreceptor degeneration has not yet occurred. As controls, some rats received injections of cell culture medium alone, or were not injected. Tests for visual function were performed at 60 and 90 days after birth, times at which loss of photoreceptor cells has produced characteristic vision deficits. As more fully described in the paper, test results of relative visual acuity demonstrated that animals receiving hES-derived RPE cells performed significantly better than cell culture medium treated or untreated controls. Treated animals showed a 50 percent improvement over medium-treated controls and a 100 percent improvement over untreated controls in visual performance. Visual acuity was approximately 70 percent of normal rats.

"One important advantage offered by hES-derived cells over other cells developed to mimic or replace lost retinal pigment epithelium is that they more closely resemble primary human RPEs," stated Raymond D. Lund, Ph.D., Professor at the Moran Eye Center, University of Utah Health Science Center, Salt Lake City and the study's lead author. "Another significant advantage of using these cells is that a range of lines can be derived allowing the opportunity to 'tissue match' donor cells with recipient, a real advantage given that RPE cells are highly immunogenic and susceptible to rejection without some form of immunosuppression."

"Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement cells for clinical studies," stated Robert Lanza, M.D., Vice President of Research & Scientific Development at ACTC and senior author of the paper. "All 18 human embryonic stem cell lines we studied reliably produced retinal cells that could potentially be used to treat retinal degenerative diseases, such as macular degeneration. We showed that these cells have the capacity to rescue visual function in animals that otherwise would have gone blind. Importantly, the cells did not appear to cause any unwanted pathological responses in the animals following transplantation."

"We are working to generate clinical grade RPE cells from human embryonic stem cells under controlled GMP conditions," said Irina Klimanskaya, Ph.D., Director of Stem Cell Biology at ACTC, and the author who initiated this work. "However, more research is still required to optimize their performance and to assure they are safe for clinical trials."

"We are encouraged by this data related to our retinal program and are focused on driving therapies to the clinic," stated William M. Caldwell IV, CEO of ACTC.

Other authors include Shaomei Wang, Toby Holmes, Bin Lu, N. Bischoff, and Sergej Girman of the Moran Eye Center; Rebeca Ramos-Kelsey of Advanced Cell Technology, and Yves Sauve of the Ophthalmology and Physiology Dept., University of Alberta, Edmonton.

About Advanced Cell Technology, Inc.

Advanced Cell Technology Inc. is a biotechnology company applying embryonic stem cell technology in the emerging field of regenerative medicine. The company operates facilities in Alameda, California and Worcester, Massachusetts. For more information about the company, please visit http://www.advancedcell.com.