Further to the featured ophthalmic stem cell work featured on the blog by Ocata, BTX Hadasit, RIKEN, U.C. London & The Neural Stem Cell Institute the below article looks to provide a window into the broadening field of SC research related to the eye.
Sight Restoration Research - Pioneering Work in Regenerative Medicine
Two related science developments this month illustrate the expanding potential of cellular biology to offer possible solutions for tissue regeneration. Both investigative teams published their work in Nature and they represent bookends in the field of potential treatments for sight preservation and restoration, a leading edge segment of the emerging regenerative medicine sector.
The first research article¹ from the Osaka University Graduate School of Medicine (Japan), in association with Cardiff University, reported the development of a complex eye tissue structure from which specific cell types can be used. The method illustrates that self-forming mini organ bud like layers of distinct cell lineages can be successfully grown from pluripotent cells in the lab, replicating in principle some of the processes of embryonic whole eye development. The tissue structure was created using reprogrammed adult cells and produced various ocular cellular layers which were identified as corneal, lens, neural retina and RPE. To confirm cell lineage capability the corneal cells were isolated, expanded and tested in a rabbit model of corneal blindness. The corneal sheet transplants successfully restored functional sight in the animals showing proof of concept.
This achievement is illustrative of broad progress in the field pioneered by developmental biologists working on recreating complex tissue structures. This earlier work inspired many and has led to the adoption of similar lab techniques to coax organ-like micro environments to self-form using pluripotent stem cells for research, screening and therapeutic translation.
The second article² by researchers at Sun Yat-sen University in China, in collaboration with US scientists, demonstrated that by rewriting the surgical technique for standard cataract removal it was possible to maintain the inherent capacity of resident lens stem cells to regrow lost tissue and restore a natural lens with functionality after surgery. The current clinical procedure, it was discovered, limits the potential for self healing as a result of the loss of specific local regenerative cells during the intervention. By modifying the incision and cataract removal procedure to a minimum the researchers were able to preserve the lens chamber integrity and allow the natural in-situ cellular repair mechanism to regenerate the lens. The studies were conducted successfully in rabbits, non-human primates and notably in 12 infants with congenital cataracts.
The ability to activate the body’s own natural regenerative potential via local reservoirs of tissue specific stem cells is a promising area of developmental research. Speaking to this Professor Julie Daniels at University College London’s Department of Regenerative Medicine and Cellular Therapy commented on the work saying the study “opens up the possibility of therapeutic manipulation of the broader stem-cell environment in the eye.”
Sight has become a focal point of cellular research given the unique accessibility of the eye as an organ, advancements in visualization and its relative immune privileged state. Recently a personalized treatment employing regrown corneal sheets with regenerative limbal stem cells, called Holoclar, received approval in Europe for eye surface injury. In addition there are a number of other biologics now in clinical trials for sight regeneration which is indicative of the variety of potential treatment methodologies being explored.
(1) R. Hayashi et. al. Co-ordinated ocular development from human iPS cells and recovery of corneal function. Nature, 2016 Mar 17; doi: 10.1038/nature17000
(2) H. Lin et al. Lens regeneration using endogenous stem cells with gain of visual function. Nature, 2016 Mar 17. doi: 10.1038/nature17181