At 72 days, stem cells derived from human blood formed an early retina structure, with specialized cells resembling photoreceptors (red) and ganglion cells (green) located within the outer and inner layers, respectively. Nuclei of cells within the middle layer are shown in blue. These layers are similar to those present during normal human eye development. Image: University of Wisconsin-Madison
For the first time, scientists at the University of
Wisconsin-Madison have made early retina structures containing proliferating
neuroretinal progenitor cells using induced pluripotent stem (iPS) cells
derived from human blood.
And in another advance, the retina structures showed the capacity
to form layers of cells—as the retina does in normal human development—and
these cells possessed the machinery that could allow them to communicate
information. (Light-sensitive photoreceptor cells in the retina along the back
wall of the eye produce impulses that are ultimately transmitted through the
optic nerve and then to the brain, allowing you to see.)
Put together, these findings suggest that it is possible to
assemble human retinal cells into more complex retinal tissues, all starting
from a routine patient blood sample.
Many applications of laboratory-built human retinal tissues
can be envisioned, including using them to test drugs and study degenerative
diseases of the retina such as retinitis pigmentosa, a prominent cause of
blindness in children and young adults. One day, it may also be possible
replace multiple layers of the retina in order to help patients with more
widespread retinal damage.
“We don’t know how far this technology will take us,
but the fact that we are able to grow a rudimentary retina structure from a
patient’s blood cells is encouraging, not only because it confirms our earlier
work using human skin cells, but also because blood as a starting source is convenient
to obtain,” says David Gamm, MD, pediatric ophthalmologist and senior
author of the study. “This is a solid step forward.”
In 2011, the Gamm laboratory at the Waisman Center
created structures from the most primitive stage of retinal development using
embryonic stem cells and stem cells derived from human skin. While those
structures generated the major types of retinal cells, including
photoreceptors, they lacked the organization found in more mature retina.
This time, the team, led by Gamm, assistant professor of ophthalmology
and visual sciences in the UW School of Medicine and Public Health, and
postdoctoral researcher and lead author Joseph Phillips, used their method to
grow retina-like tissue from iPS cells derived from human blood gathered via
standard blood draw techniques.
In their study, about 16% of the initial retinal structures
developed distinct layers. The outermost layer primarily contained
photoreceptors, whereas the middle and inner layers harbored intermediary
retinal neurons and ganglion cells, respectively. This particular arrangement
of cells is reminiscent of what is found in the back of the eye.
Further, work by Phillips showed that these retinal cells
were capable of making synapses, a prerequisite for them to communicate with
The iPS cells used in the study were generated through
collaboration with Cellular Dynamics International (CDI) of Madison, Wisconsin,
which pioneered the technique to convert blood cells into iPS cells. CDI
scientists extracted a type of blood cell called a T-lymphocyte from the donor
sample, and reprogrammed the cells into iPS cells. Cellular Dynamics
International was founded by UW-Madison stem cell pioneer James Thomson.
“We were fortunate that CDI shared an interest in our
work. Combining our lab’s expertise with that of CDI was critical to the
success of this study,” added Gamm.
The results were published in an online issue of Investigative Ophthalmology & Visual