This image shows an ES cell-derived optic cup virtually inserted into a test tube. In a major advance in regenerative medicine, researchers have for the first time coaxed stem cells from a mammal into becoming an embryonic eye.
Credit: Riken CDB/M Eiraku and Y Sasai/AFP
An ES cell-derived optic cup formed by self-organization in 3D culture. Green color is fluorescence of GFP protein that was engineered to mark retinal tissue.
Credit: M. Eiraku and Y.Sasai at RIKEN Center for Developmental Biology
SYDNEY: Embryonic stem cells from mice can autonomously arrange themselves into a complex cup-like structure resembling a mouse’s developing eye, Japanese researchers were surprised to report.
This spontaneous behaviour and the resulting eye-like structure formed by the cells could help researchers to develop new stem cell-derived tissue and organ transplants to help treat people with retinal degenerative conditions.
“We are now well on the way to becoming able to generate not only differentiated cell types, but organised tissues from embryonic and induced pluripotent stem cells, which may open new avenues toward applications in regenerative medicine,” said study co-author Yoshiki Sasai, a developmental biologist from the RIKEN Kobe Institute in Japan.
Constructing organs a difficult task
While cell therapies are being developed to treat certain conditions such as diabetes and Parkinson’s disease – where destroyed cells can be replaced by substitutes made from stem cells – the ability to make an actual organ has been more elusive.
“Replacing organs, for example, an eye or a kidney, is a much more difficult scenario because there are multiple different cell types that need to integrate correctly with one another in a 3D environment,” explained Bernie Tuch, director of the New South Wales Stem Cell Network.
This study, published in Nature, has shown that a collection of different cell types, when provided with the appropriate stimuli, can act independently to begin forming a structure that mimics a primitive organ.
No tricks, just spontaneous formation
Researchers cultured roughly 3,000 embryonic stem cells from mice. With the addition of extracellular matrix proteins – a part of the tissue that provides structural support – the cells began to spontaneously form an eye-like structure.
Using sophisticated imaging techniques the authors confirmed that these hemispheric structures were indeed very similar to the early stages of embryonic eye development, the precursor to an actual functioning eye.
“We didn’t add any special shaping tricks, this was the result of self-organisation,” said Sasai. “After we put the cells into a homogenous culture medium they were able to communicate with each other locally to create a shape.”
“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,” he said.
Regenerative medicine on the horizon?
Andrew Elefanty, a stem cell researcher at Monash University in Melbourne, said these findings could improve the study of degenerative eye diseases and might eventually enable the growth of new cells to treat blindness, but admitted this will take time.
He said the research shows “it is possible to start to form a structure as complicated as the eye in the laboratory” and “provides a starting point for the formation of the complex nerve cell layers needed to transmit visual signals from the outside world to the brain”.
Tuch, from the NSW Stem Cell Network, said the research could have applications beyond vision. “Whilst what was described relates to the eye, it is theoretically possible the same outcomes might be achieved with other organs using different stimuli.”
The next step for the Japanese scientists is to transfer this research from mice to human ES cell cultures – a process they expect will likely take one to two years.
