The Importance of Stem Cells (a guest post from Dr. David Gamm)
Dr. David Gamm on the potential of stem cell research to benefit patients with retinal degenerations.
When I joined the University of Wisconsin (UW) in 2003, I saw stem cell research as having great potential to benefit patients with retinal degenerations. I also saw stem cells as a way to answer basic science questions about the retina and the conditions that affect it. As a scientist and a pediatric ophthalmologist, these goals were really important to me.
But to enter the field, I had to make a radical shift from my Ph.D. work and return to the drawing board. I wasn’t trained as a cell biologist – I had studied biochemistry – so I had to learn new techniques and concepts from the accomplished scientists at UW.While there clearly are challenges in this area of research, I’m very inspired by the potential of stem cells for saving and restoring vision in people with retinal degenerations. The Holy Grail for me and my colleagues is to use them to replace retinal cells that have been lost, so we can bring back some vision for those with even the most advanced disease.
We’ve made considerable strides toward that goal in a short amount of time. To think that a little more than decade ago, the entire field of stem cell biology was discovered, and now we already have human studies underway – that’s truly remarkable compared to other fields of science and medicine.
The power of stem cells is twofold: 1) They have the ability to become any cell type in the body, including retinal cells; and 2) They have the ability to self–renew, so that virtually limitless supplies of them can be made. Stem cells are said to be “pluripotent” if they possess these two qualities.
Dr. Jamie Thomson, my colleague at UW, discovered the first human pluripotent stem cells in 1998. They were obtained from blastocysts that were left over from in vitro fertilization. These are commonly referred to as embryonic stem cells.
Another big advancement in the field came in 2006 and 2007, when Jamie and scientists from Japan genetically reprogrammed, or induced, mature cells from skin to become pluripotent. This provided a new source of stem cells, called induced pluripotent stem cells (iPSC), which offer many practical advantages and don’t raise the ethical concerns sometimes associated with embryonic stem cells.
While my colleagues and I work with both embryonic stem cells and iPSC, the latter are unique in that the patient can serve as his or her own source of stem cells. This could greatly increase the chance that these cells will survive, integrate and function without sparking an immune reaction. They could, in other words, serve as a customized treatment for the patient.
Collaborating with Jamie and Dr. Sara Howden more than a year ago, we were able to take skin cells from a 27-year-old woman with a retinal disease called gyrate atrophy and reprogram them back to an embryonic-like state. We then corrected the genetic defect causing the retinal disease — something that had not been done previously— before directing them to become retinal cells. That, as you might expect, was a big breakthrough for us. Recently, we used a patient’s blood cells to develop layered retinal tissue that is closer to being suitable for transplantation back into the eye.
The challenge that lies ahead is transplanting these cells back into the patient and getting them to survive, integrate and restore vision. We’re making meaningful progress and exploring innovative ways, including the development of scaffold-like structures, to do this. It isn’t easy, and it won’t happen overnight, but I am encouraged by the advancements that we and other FFB-funded labs are achieving.
We are also using iPSC, without correcting the genetic defect, to study the underlying retinal degeneration process in a lab dish and figure out how different types of RP lead to vision loss. In turn, we can explore how well different treatments work in saving these cells and, ultimately, vision. Again, all this is happening in a dish using human cells, which are a critical tool for understanding human disease. These are important applications of iPSC not only for us, but for researchers around the world studying a variety of conditions.
I’d be remiss if I didn’t mention that the Foundation believed in the potential of stem cells at a very early stage, long before their power was demonstrated. Fortunately, it also believed in me when I was just starting out in this field. While I’m grateful for that support, mostly I’m excited about what we are doing to help patients. We are, no doubt, on the right path to saving vision.
David Gamm, M.D., Ph.D., is a Foundation-funded researcher at the University of Wisconsin-Madison, where he is also an assistant professor of ophthalmology and visual sciences and the Edwin & Dorothy Gamewell Professor at the UW Eye Research Institute.