A team of researchers from Sun Yat-sen University in China and here in California at my graduate alma mater UCSD has published a remarkable, new report in Nature reporting human lens regeneration in cataracts. This is a truly amazing idea that endogenous stem cells can regrow new lenses. I wonder if we are on a path to someday make entire new eyes via stem cells in future decades.
In the Lin, et al. paper entitled, “Lens regeneration using endogenous stem cells with gain of visual function”, the team describes how a cataract surgery that preserves endogenous lens stem cells in the lens capsule, allows for lens regrowth after surgery. They were able to do this in animals and in human infants.
The key seems to be preservation of what they call “lens epithelial stem/progenitor cells” or LECs. Conventional cataract surgery fails to preserve LECs and involves insertion of an artificial lens. In this new approach the researchers let the LECs regenerate a new lens. See Figure 2 from the paper above. You can also see the table on the human patient data from the clinical trial here.
They end their article on an optimistic note:
“In summary, the current surgical procedure for cataract treatment inadvertently destroys the integrity of the lens capsule and the very LECs that hold the regenerative key to lens restoration. It is also associated with numerous side-effects and a significant risk of complications, particularly in infants. To overcome these problems, we have developed a new, minimally invasive surgical method that allows regeneration of a functional lens with refractive and accommodative abilities, and with greater visual axis transparency. This new cataract treatment uses endogenous stem cells to replenish the human ocular lens, and provides a fresh paradigm for organ and tissue regeneration.”
There are remain at least three billion-dollar open questions.
- What will happen to these lens over time as the infants grow up? If their vision is poor compared to those receiving artificial lenses then that’s going to be much less exciting.
- Will this approach work in older folks, who make up the vast majority of cataract patients? Infants could well have an enormous stockpile of LECs, whereas as we age these cells could disappear…but then again, maybe not. Maybe even those of us decades into life have enough LECs to grow news lens.
- Could these cells be used to make replacement lens via bioengineering in the lab that could then be transplanted to replace lenses with cataracts? Long term this seems like the most promising route rather than relying upon the vagaries of endogenous regrowth, particularly if the answer to the first question is “no”.
Overall this is an exciting paper and once I get the current grant I’m working on done, I have this paper on my list for a more thorough read.
Paul – this is a surprising development and one which deserves the attention it is getting.
To help young children with sight issues in this way is Huge and if it can be extended to be a potentially superior treatment approach to standard of care for the main group that suffers, i.e. the older population with cataracts, would be a monumental breakthrough.
This now adds to the efficacy story that the Limbal cell therapy started and perhaps will be added to when Sally Temple & Derek van der Kooy et al teams enter the clinic.
Will be interesting to see if others replicate the work now and report.
I have to agree with your sentiment about moving towards regenerating the entire eye as there is a good deal of work being done on organoids in that area. An interesting paper on this general complex tissue topic coincidentially came out yesterday by the Japanese entitled: “Co-ordinated ocular development from human iPS cells and recovery of corneal function” (link below)
Generally an excellent development for the space!
Cheers
Michael
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17000.html?elqTrackId=77fa8b0abf524ed9bad191a1de283d26&elq=cc0848f10e0c4e9798c09313ec3c5f3f&elqaid=14923&elqat=1&elqCampaignId=5#affil-auth
@Deepa Bhartiya. Very few people still believe in VSELs, especially after these two strong papers in 2013: http://www.ncbi.nlm.nih.gov/pubmed/?term=vsel+weissman, http://www.ncbi.nlm.nih.gov/pubmed/23696815. VSELs seem to be more of a technical artifact, than anything involved in the regeneration process.
Wonderful achievement. I recently heard a visionary in the field mention that regeneration has to occur from within – replacing diseased cells by stem cells differentiated in a Petri dish will not work in the long run. This paper proves the point. But I am sure that it is not only the LECs but LECs+VSELs that have made it possible. Our papers do not find a place in Nature or equivalent journals, but we have also shown that culture of endogenous ovary surface epithelial cells (http://www.ncbi.nlm.nih.gov/pubmed/21291304) and chemoablated testicular cells (http://www.ncbi.nlm.nih.gov/ pubmed/25903688) spontaneously differentiate into oocytes and sperm. There is no need to differentiate ES/iPS cells in a dish to make eggs/sperm. We have obtained pancreatic progenitors from human ES cells and seen their potential in mice after transplanting in immuno-isolatory device. But rather than moving to the clinic – we are trying to study if a diabetic pancreas can be regenerated from endogenous VSELs+pancreatic progenitors.
Great article! Do you think the attachment of the bioengineered lens would have any complications associated with it?