Groundbreaking research in Japan has demonstrated that embryonic stem cells floated in a specific chemical solution can spontaneously form into optic cups, the precursors of the eye. The research could be the ‘holy grail’ that enables scientists to understand much more about eye diseases, and one day, discover cures.
Douglas Sipp, from the RIKEN CDB, told mivision that the research “has shown that embryonic stem cells (ESCs) have the inherent ability to self-organise into a complex 3D structure, comprising multiple cell types, without requiring any external signalling source.”
Associate Professor Nick Di Girolamo, Director of Ocular Research at the School of Medical Studies UNSW, who has developed a stem cell therapy for corneal blindness, spoke to mivision about the research: “These are exciting developments in stem cell and tissue regeneration fields. The authors have harnessed the power of embryonic stem cells to the next level by creating the beginnings of a complex organ, the eye.
“The study addresses several important issues, including furthering research into developing novel therapies for retinal disease and growing ocular tissue parts in view of shortages in donor eye tissue. Moreover, the same principles that govern oculogenesis may be applied to develop other vital organs,” said A/Prof. Di Girolamo.
Douglas Sipp, from the RIKEN CDB, told mivision that the research has shown that embryonic stem cells (ESCs) have the inherent ability to self-organise into a complex 3D structure, comprising multiple cell types…
The research has been carried out by Mototsugu Eiraku, deputy leader of the Four-dimensional Tissue Analysis Unit and colleagues in the Laboratory for Neurogenesis and Organogenesis (Group Director, Yoshiki Sasai), as well as the RIKEN VCAD Program, and Kyoto and Osaka Universities. The team nurtured aggregates of mouse embryonic stem cells in a special culture medium in the presence of structural support proteins in a laboratory setting. Importantly, the cells under investigation were able to differentiate and self-assemble into retina-like cells and tissue. However, other critical ocular components such as the optic nerve, lens and cornea were not observed.
In 2010, Prof. Hans Kierstead at the University of California Irving announced that his team had developed a “three-dimensional, retina-like structure out of human embryonic stem cells.”
In Prof Kierstead’s study, researchers first created two types of cells from the human embryonic stem cells: early-stage retinal cells, and retinal pigment epithelium (RPE) cells, which provide nourishment to the cells responsible for vision in the retina. The researchers then grew these two types of cells together in a chamber designed to expose them to a gradient of concentrations of solutes and growth-promoting chemicals.
“In the past it was generally believed that retina formation required signals from adjacent tissues, such as the lens. The Kierstead group, and others (including labs at the RIKEN CDB), showed previously that it was possible to differentiate pluripotent stem cells into retinal cells, both neurons and retinal pigmented epithelium. These were not, however, organised into complex tissue-like structures,” said Mr. Sipp.
Yoshiki Sasai, Group Director of the study said, “What we’ve been able to do in this study is resolve a nearly century-old problem in embryology, by showing that retinal precursors have the inherent ability to give rise to the complex structure of the optic cup. It’s exciting to think that we are now well on the way to becoming able to generate not only differentiated cell types, but organised tissues from embryonic stem and induced pluripotent stem cells (iPS), which may open new avenues toward applications in regenerative medicine.”
“The Sasai achievement is interesting both in what it tells us about the developmental potential of pluripotent stem cells, and in possible future applications in disease modelling and providing a solid scientific foundation for the development of regenerative medicine in the future,” commented Mr. Sipp.
However he told mivision, “it is likely that research into the regeneration of the pigmented epithelium, such as has been proposed in the Advanced Cell Technology’s clinical trial, will proceed more quickly than regeneration of neural tissue, which in order to be functional would need to connect into pre-existing neuronal networks in the patient’s body.”
The U.S.A based company Advanced Cell Technology (ACT) commenced the world’s second ever clinical trial using embryonic stem cell therapy in November 2010. The trial is examining the safety of a treatment for Stargardts Macular Degeneration.