Visual Function Rescued in Rats Using Cells Derived From iPS Cells

Don Gibbons, PhD*

Induced pluripotent stem (iPS) cells have created both excitement and head scratching ever since they were first created a little over two years ago. The excitement arises from their creation through reprogramming adult cells to acquire the properties of embryonic stem cells without using a human embryo. IPS cells may also have the added benefit of overcoming any rejection issues typically associated with the transplantation of organs and tissue, as the stem cells would be derived from one’s own tissues. But determining just how identical the induced stem cells are to embryonic stem cells in function has caused much consternation.

Now, a team at University College London, UK and University of California Santa Barbara, USA has provided some insight into this.

These researchers used a rat model for age-related macular degeneration (results in blindness) in which defects in the retinal pigmented epithelial (RPE) cells, the cells that ultimately give rise to more mature cell types in the eye, lead to death of photoreceptors.

Specifically, the researchers transplanted RPE cells grown from iPS cells into the rat’s retina and showed that these cells were able to prevent the photoreceptors from dying. The rats retained their vision.

A press release from UCSB quoted Sherry Hikita, an author on the paper saying: "Although much work remains to be done, we believe our results underscore the potential for stem-cell based therapies in the treatment of age-related macular degeneration."

However, the team also saw a difference between RPE cells grown from iPS cells and those from embryonic stem cells used in earlier experiments. Unexpectedly, the embryonic stem cell-derived cells survived long-term after transplant, where as the iPS-derived RPE cells suffered rejection by the immune system. While this would not occur if the cells were derived from the patient receiving the therapy, many leaders in the field have hoped that banks of iPS cells could be developed that would be less expensive and time-consuming than deriving new cells for each patient. Also, these banked cells could avoid transplanting cells with the same genetic mutation that caused the problem in the first place.

In the report (1), December 3 PLoS ONE the authors speculate: "The embryonic origin of human embryonic stem cell-derived RPE may reflect a more immune privileged cell type in comparison to iPS [cell-derived]-RPE."

To further complicate the equation, the rats in this model retained long-term visual function despite rejection of the transplanted cells suggesting the transplanted cells induced some sort of protective response for RPE cells in the surrounding tissue.

Scores of labs around the world are actively investigating the differences between iPS cells and embryonic cells and trying to determine if these differences will matter clinically. Growing RPE cells to repair macular degeneration may be one of the first clinical areas where those questions are answered.

*Author Affiliation
Don Gibbons, PhD
Chief Communications Officer
California Institute of Regenerative Medicine
California, USA

Notes
1. Carr, A. J., Vugler, A. A., Hikita, S. T., Lawrence, J. M., Gias, C., Chen, L. L., Buchholz, D. E., Ahmado, A., Semo, M., Smart, M. J., et al. (2009). Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 4, e8152.

Posted March 12, 2010