University of Wisconsin-Madison School of Medicine scientists have successfully grown multiple types of retina cells from two types of stem cells, suggesting a future in which damaged retinas could be repaired by cells grown from the patient's own skin.

"This is an important step forward for us, as it not only confirms that multiple retinal cells can be derived from human induced pluripotent stem cells using this approach, but also shows how similar the process is to normal human retinal development," lead researcher David Gamm says. "That is quite remarkable given that the starting cell is so different from a retinal cell and the whole process takes place in a plastic dish. We continue to be amazed at how deep we can probe into these early events and find that they mimic those found in developing retinas. Perhaps this is the way to close the gap between what we know about building a retina in mice, frogs and flies with that of humans."

Gamm says the work built on the strong tradition of stem cell research at University of Wisconsin-Madison School of Medicine. James Thomson announced that he had made human stem cells from skin, called induced pluripotent stem cells (iPS), in November 2007. Su-Chun Zhang was among the first to create neural cells from embryonic stem cells. Zhang was also part of the Gamm lab's retinal study. Meyer says the retina project began by using embryonic stem cells, but incorporated the induced pluripotent stem cells as they became available. Ultimately, the group was able to grow multiple types of retina cells beginning with either type of stem cell, starting with a highly enriched population of very primitive cells with the potential to become retina. This is critical, as it reduces contamination from unwanted cells early in the process. In normal human development, embryonic stem cells begin to differentiate into more specialized cell types about five days after fertilization. The retina develops from a group of cells that arise during the earliest stages of the developing nervous system. The Wisconsin team took cells from skin, turned them back into cells resembling embryonic stem cells, then triggered the development of retinal cell types.

"This is one of the most comprehensive demonstrations of a cell-based system for studying all of the key events that lead to the generation of specialized neural cells,'' Meyer says. "It could serve as a foundation for unlocking the mechanisms that produce human retinal cells."

Because the group was successful using the induced pluripotent stem cells, they expect this advance to lead to studying retinal development in detail and treating conditions that are genetically linked. For example, skin from a patient with retinitis pigmentosa could be reprogrammed into induced pluripotent stem cells, then retina cells.

Likewise, someday ophthalmologists may be able to repair damage to the retina by growing rescue or repair cells from the patient's skin. Earlier this year, scientists from the University of Washington showed that human embryonic stem cells had the potential to replace retinal cells lost during disease in mice.

"We're able to produce significant numbers of photoreceptor cells and other retinal cell types using our system, which are lost in many disorders," Meyer says. Photoreceptors are light-sensitive cells that absorb light and transmit the image as an electrical signal to the brain.

The team had similar success in creating the multiple specialized types of retina cells from embryonic stem cells, underscoring the similarities between embryonic stem cells and induced pluripotent stem cells. However, Gamm emphasizes that there are differences between these cell types as well. More work is needed to understand their potential and their limitations.
References:
1. David Gamm, et al. Proceedings of the National Academy of Sciences.

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