Retinal tissues regenerated with skin stem cells

ScienceDaily (May 16, 2011) — Scientists from Schepens Eye Research Institute are the first to regenerate large areas of damaged retinas and improve visual function using IPS cells (induced pluripotent stem cells) derived from skin. The results of their study, which is published in PLoS ONE this month, hold great promise for future treatments and cures for diseases such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and other retinal diseases that affect millions worldwide.

"We are very excited about these results," says Dr. Budd A. Tucker, the study's first author. "While other researchers have been successful in converting skin cells into induced pluripotent stem cells (iPSCs) and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected," he adds. Tucker, who is currently an Assistant Professor of Ophthalmology at the University of Iowa, Carver College of Medicine, completed the study at Schepens Eye Research Institute in collaboration with Dr. Michael J. Young, the principle investigator of the study, who heads the Institute's regenerative medicine center.

Today, diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are the leading causes of incurable blindness in the western world. In these diseases, retinal cells, also known as photoreceptors, begin to die and with them the eye's ability to capture light and transmit this information to the brain. Once destroyed, retinal cells, like other cells of the central nervous system have limited capacity for endogenous regeneration.

"Stem cell regeneration of this precious tissue is our best hope for treating and someday curing these disorders," says Young, who has been at the forefront of vision stem cell research for more than a decade.

While Tucker, Young and other scientists were beginning to tap the potential of embryonic and adult stem cells early in the decade, the discovery that skin cells could be transformed into "pluripotent" cells, nearly identical to embryonic cells, stirred excitement in the vision research community. Since 2006 when researchers in Japan first used a set of four "transcription factors" to signal skin cells to become iPSCs, vision scientists have been exploring ways to use this new technology. Like embryonic stem cells, iPSCs have ¬the ability to become any other cell in the body, but are not fraught with the ethical, emotional and political issues associated with the use of tissue from human embryos.

Tucker and Young harvested skin cells from the tails of red fluorescent mice. They used red mice, because the red tissue would be easy to track when transplanted in the eyes of non-fluorescent diseased mice.

By forcing these cells to express the four Yamanaka transcription factors (named for their discoverer) the group generated red fluorescent IPSCs, and, with additional chemical coaxing, precursors of retinal cells. Precursor cells are immature photoreceptors that only mature in their natural habitat -- the eye.

Within 33 days the cells were ready to be transplanted and were introduced into the eyes of a mouse model of retina degenerative disease. Due to a genetic mutation, the retinas of these recipient mice quickly degenerate, the photoreceptor cells die and at the time of transplant electrical activity, as detected by ERG (electroretinography), is absent.

Within four to six weeks, the researchers observed that the transplanted "red" cells had taken up residence in the appropriate retinal area (photoreceptor layer) of the eye and had begun to integrate and assemble into healthily looking retinal tissue.

The team then retested the mice with ERG and found a significant increase in electrical activity in the newly reconstructed retinal tissue. In fact, the amount of electrical activity was approximately half of what would be expected in a normal retina. They also conducted a dark adaption test to see if connections were being made between the new photoreceptor cells and the rest of the retina. In brief, the group found that by stimulating the newly integrated photoreceptor cells with light they could detect a signal in the downstream neurons, which was absent in the other untreated eye.

Based on the results of their study, Tucker and Young believe that harvesting skin cells for use in retinal regeneration is and will continue to be a promising resource for the future.

The two scientists say their next step will be to take this technology into large animal models of retinal degenerative disease and eventually toward human clinical trials.

Oh good, I'll be able to throw away my glasses soon.

Oh good, I'll be able to throw away my glasses soon.

If you're rich enough to.

Oh good, I'll be able to throw away my glasses soon.

Erradication of glasses would make me sadfais.

Glasses are awesome.

Oh good, I'll be able to throw away my glasses soon.

So your vision problems stem from a damaged retina and not lens/eye shape problems?

This article made my day. My dad (and his sister) has RP, so I'm hoping that this research leads to some tangible results that might help him and everyone else who has a disease that damages the retina sometime in the future.

I told my mom about this and she cried; she was so happy that some progress has been made in this field. Made me tear up a bit, too. :>

*Yawns*

What? Another iPS cell treatment possibility news?

Wake me up when it's officially allowed in the clinic.

 Spoiler

You know what I REALLY don't like? It's to give people so much hope, only to collapse it because of complications. Already we have complications from certain iPS treatment in which the patient rejects the graft. All it takes is one such case during phase II and the treatment would be subject to severe studying. If I'm your mum I would be very happy too, but I would also be quite disappointed if this became false hope. Of course I could take it that as good as nothing really happened, but not to others.

Hadriel

Oh good, I'll be able to throw away my glasses soon.

wait what, i thought glasses were used for lens correction not the actual retina itself o.o

*Yawns*

What? Another iPS cell treatment possibility news?

Wake me up when it's officially allowed in the clinic.

 Spoiler

You know what I REALLY don't like? It's to give people so much hope, only to collapse it because of complications. Already we have complications from certain iPS treatment in which the patient rejects the graft. All it takes is one such case during phase II and the treatment would be subject to severe studying. If I'm your mum I would be very happy too, but I would also be quite disappointed if this became false hope. Of course I could take it that as good as nothing really happened, but not to others.

Hadriel

You'd prefer it to be ignored, just like you did, by the way, so people never know of its existence, and nobody bothers to fund it?

Dammit, give everyone a break, it's just a result of something, that can become future commonplace stuff.

To immediately invoke the negative of what I said is obviously wrong.

Do you know how many drugs and treatments go through clinical trials and fail? Take any one of them and wave a wand and there you have a report that's not too far off from this. What's the point of the hype? Who said that nobody would bother to fund it? This is a different case from DCA, where it's a non-patentable compound. iPS cells are a whole different story, one with lots of hope and lots of media publicity but rare few articles are ever unbiased/tells people enough what they should know/doesn't contain misleading information/all of the above.

There is absolutely no difference in giving a trial drug media publicity and keeping it behind closed doors - failure and success is independent of such hype. Unless you're talking about politics and/or religion [ethics is a different story], which we really frown on.

Hadriel

You'd prefer it to be ignored, just like you did, by the way, so people never know of its existence, and nobody bothers to fund it?

Dammit, give everyone a break, it's just a result of something, that can become future commonplace stuff.

You obviously don't know how pharmaceutical companies work, so before you find out, I suggest you stop making blind assumptions on groundless anger, and worse, attacking people who are actually capable of making informed opinions.

And for common sense sake, you're seriously asking people/some government to pay these scientists from out of their own pockets so that they can gamble the money into testing this drug that might not even end up successful?

I should start my own basement lab and ask everyone in the world to come and fund me after I've made initial "successes" and cry for media attention.

You know what I REALLY don't like? It's to give people so much hope, only to collapse it because of complications. Already we have complications from certain iPS treatment in which the patient rejects the graft. All it takes is one such case during phase II and the treatment would be subject to severe studying. If I'm your mum I would be very happy too, but I would also be quite disappointed if this became false hope. Of course I could take it that as good as nothing really happened, but not to others.

She was happy for "Some progress," not tangible results. I really think you can't understand how much a tiny step in the right direction is appreciated until you've lived with a person suffering from the disease they're trying to cure (I'm not saying you haven't; this is simply how I feel. I have no intent to offend in the least). Sure, it's small and it may amount to nothing, but hell, it's something. If everyone just gave up and said "NOPE NOTHING IS GOING TO WORK SORRY" we will never progress. I can't agree with the attitude that I have perceived from you from this post. I may seem overly optimistic, but I just come off that way arguing the more optimistic side of the point. Besides, the sort of progress necessary for real results will happen in a university lab, not a pharmaceutical one.

One more thing - iPS cell grafts will not suffer from rejection. The iPS cells are cells taken from the patient the grafts are used on, so there is no chance of rejection.

[...] Besides, the sort of progress necessary for real results will happen in a university lab, not a pharmaceutical one.

One more thing - iPS cell grafts will not suffer from rejection. The iPS cells are cells taken from the patient the grafts are used on, so there is no chance of rejection.

The above stated are not true. A great deal of drugs came from research at pharmaceutical labs. But yes it is also true that many of the new developments come from universities and research institutes, but you still need pharma labs to do the majority of the drug research.

And I am way ahead of you. I do happen to have access to the latest news.
http://www.sfgate.com/cgi-bin/article.cg...1JG69R.DTL
http://www.nature.com/news/2011/110513/f...s=news_rss
doi:10.1038/nature10135
You think so now?

The immediate negative of what I said will not be true. Who said that everyone is going to give up? This is what I want: tell me something when a treatment passes the phase II trials - those would have much more hope, and can be used on [a limited number of] patients.

Hadriel

You obviously don't know how pharmaceutical companies work, so before you find out, I suggest you stop making blind assumptions on groundless anger, and worse, attacking people who are actually capable of making informed opinions.

And for common sense sake, you're seriously asking people/some government to pay these scientists from out of their own pockets so that they can gamble the money into testing this drug that might not even end up successful?

I should start my own basement lab and ask everyone in the world to come and fund me after I've made initial "successes" and cry for media attention.

Sure, let's not inform about anything then. Better? Less of a nuisance, right?

That is, in fact, for the better. Keep the press out of clinical trials unless absolutely necessary. The advertisements for approved treatments and drugs and stuff will come naturally.

Stop trying to throw an absolute negative of what we say. It contributes little.

Hadriel

That is, in fact, for the better. Keep the press out of clinical trials unless absolutely necessary. The advertisements for approved treatments and drugs and stuff will come naturally.

Stop trying to throw an absolute negative of what we say. It contributes little.

Hadriel

I'm not looking at the negatives. In fact, you are the one who just says to not discuss this at all. And that contributes even less.

I said: Don't tell me about these reports until they're past Phase II. Well, they've now told us about the report, haven't they? So what's wrong with discussing it? You said: Don't tell them anything at all, as a response to me saying that the media should stop giving the public too much biased information leading to false hope. Tell me how you are being constructive.

The people who want to know more about all these stuff can go read the journals [and science blogs]. But there is a difference between raising the scientific awareness of the general public, and advertising, and knowing when AND what to tell them is difficult too. It's no different from telling the public about a new "Magic bullet" against ____ disorder - that's utter rubbish for us who know what's going on.

The scientific community cannot be totally isolated from the public, granted, but there's little need for additional media publicity. Especially when there are so many scientific blogs out there.

Hadriel