Stem cells and diabetes are old friends, and if you’ve spent any time reading about diabetes, you probably have at least a vague sense that stem cells are important for a cure for diabetes.
As a diabetic, then, I was pleased to attend the World Stem Cell Summit in Pasadena, where scientists, doctors, business people, policy wonks, and patient advocates convened to discuss the ever-exciting field of stem cell science. The topics ranged from the bench to the bedside, covering the cutting edge in molecular biology, translational progress, and business opportunities. And many of the big-name experts in the field came to speak.
At the conference, I heard about amazing progress being made towards modeling neurological disease, regenerating heart tissue, growing kidneys, and even curing HIV. Even with so many stem cell applications to talk about, though, diabetes was no small player, and I was surprised by how much I didn’t know about diabetes and stem cells.
I had heard about the hope for beta cell regeneration, in which stem cells would be differentiated into beta cells and implanted into diabetics so that we could essentially regrow our defunct pancreases. This source of beta cells would be far more renewable and therefore preferable to the current source– pancreases from cadavers, which are very hard to come by.
Beta cell regeneration, I learned, is only one facet of the diabetes/stem cell friendship. Before I get to what stem cells can do for us, though, it’s important to cover some basics.
Terminology: So what is a stem cell, anyway?
Stem Cell: Stem cells are cells that have several particular properties:
- They are capable of self-renewal, which means a cell can divide and produce more cells without itself becoming a different type of cell.
- They are not specialized—that is, they can’t perform operations specific to a certain kind of tissue or organ, like pumping blood through an artery or forming skeletal structures.
- They can differentiate into specialized cells, usually through asymmetric division that results in one mother stem cell and a daughter cell that has begun down the multi-step path of becoming a tissue- or organ-specific cell.
Somatic Cell: Somatic cells are the cells that make up an organism other than stem cells—skin cells, muscle cells, neurons, macrophages, osteoblasts, and so on. These are the normal, non-stem cells.
Differentiation: Differentiation is the process by which a stem cell divides, producing a daughter cell that is one step farther down the specialization tree. The daughter cell itself might be another progenitor cell, capable of dividing into several different types of cells, each of which has more tissue-specific proteins and characteristics.
Adult vs. Embryonic Stem Cells: Embryonic stem cells are those derived from the early stages of fetal development. These pluripotent cells can differentiate into any tissue type, but they do not stick around once the organism is formed. Adult stem cells, on the other hand, are the multipotent progenitors like hematopoietic stem cells that are maintained throughout life, and can be extracted from the bone marrow and a number of other specialized niches within the body.
Autologous vs. Allogenic Stem Cells: As with organs and blood, you can’t just take any stem cell and stick it in any organism—the transplanted cells have to be sufficiently genetically similar to the recipient that the recipient’s immune system does not mount an attack against the cells. This can be done in two ways right now: either by finding cells of a similar genetic makeup (from relatives or close genetic matches), or by using cells from the person’s own body. Cells of a sufficiently similar genetic background we call “allogenic,” and if the cells used are from the intended recipient himself, we call the cells “autologous.”
Induced Pluripotent Stem Cells (iPSCs):iPSCs are magic. Not really, but almost. Since the 1950s, scientists have been able to turn somatic cells back into pluripotent stem cells, but generally that required transferring in the nuclei of embryonic cells, or fusing embryonic cells with the target cell. However, in 2006, Shinya Yamanaka showed that normal skin cells—fibroblasts—could be reprogrammed into pluripotent cells simply by transfecting in four genes (Oct4, Sox2, Klf4, and c-myc) and forcing their expression*. The four genes become four proteins that, when active in the cell, turn on the transcriptional programs that are necessary for pluripotency. In other words, Yamanaka figured out that there are four key proteins, that, when turned on, make any normal cell act like a stem cell, capable of both self-renewal and differentiation. The brilliance of this is that if we have an easy way to make stem cells from tissue-specific cells, we can theoretically take some skin cells from a person, turn them into stem cells, turn the stem cells into any cell we want (say, a heart tissue cell), and put it back into the person. In theory, because these cells are autologous stem cells, made from the recipient’s own body, immune rejection of the transplanted cells is much less likely, and the supply of the cells would be virtually limitless. In theory, of course—it turns out the actuality is much more complicated, but that’s a story in itself, so I’ll save it for another day.
Stem Cells and Diabetes: But What About Me?
Okay, so we have these stem cells; what does this mean for me as a diabetic? Currently, there are a number of promising uses of stem cells for treating and potentially curing diabetes—here are a few I heard about at the World Stem Cell Summit:
Beta-cell regeneration: This is probably the most well known of the potential uses of stem cells in the diabetes space. The basic idea is that we, as type 1 diabetics or later-stage type 2 diabetics, do not have functioning beta cells. Rather than just trying to be beta cells ourselves and inject exogenous insulin, why not put in new beta cells?
One way to do this is pancreas transplants, or islet transplants. This is done today, with varying degrees of success; some recipients report gradual loss of function of the transplanted cells, while others have been going strong now for up to ten years. In either case, though, recipients must take immunosuppressants, as with any organ transplant, and that carries with it a whole new set of problems for the patient. Further, donor islets are very hard to find; usually they come from the cadavers of those who opted for organ donation. Islets can also come from other species like pigs, but then we’re compounding the immune rejection issue.
So that’s where stem cells come in. Many groups, including the lab of MeriFirpo at the University of Minnesota, are actively working on ways to efficiently take somatic cells, convert them into iPSCs, and differentiate them down to insulin-producing beta cells. If this could be done in a consistent and reproducible way, it would serve as a plentiful, autologous source of beta cells for diabetics. Similarly, some labs, like that of Shimon Efrat at the Tel-Aviv University in Israel, aim to create insulin-producing cells from autologous adult stem cells like liver progenitor cells.
ViaCyte, a San Diego-based company, is taking a different approach; rather than relying on the creation of personalized iPSCs, they hope to encase embryonic stem cells in a protective envelope that can then be transplanted in to the recipient. The challenge ViaCyte is aiming to overcome is that the stem cell development process needs to be done in a reliable, industrialized fashion such that it can be profitable. So, ViaCyte is using a stable, well-characterized line of human embryonic stem cells that are cultured for two weeks, differentiated into progenitor cells, frozen for transport if necessary, encapsulated in a biocompatible envelope, and, in theory, implanted. The envelope system is designed to protect the cells from immune rejection, thereby circumventing the need for genetic matching.
Both of these approaches have some ways to go before we see them in practice in humans, but animal studies have shown promising results, and Eugene Brandon of ViaCyte said they hoped to start conducting human trials within the next few years.
Stem cell models: A related issue to beta cell regeneration is that of beta cell molecular function—how can we study what exactly is going wrong in human beta cells given that we can’t just take samples from live diabetics? One way is to use animal models, and this has been crucial in pushing forward our understanding of the human disease. Further insight can be gained in a cell culture dish, if we can observe not actual, primary beta cells, but rather stem cells that have been differentiated into beta cells and then induced to have diabetes-like symptoms. Such model systems can give us an up-close look at the mechanisms involved in beta cell maintenance and death.
Wound healing: In addition to cures for diabetes itself, stem cells are being applied to curing some of the complications associated with diabetes. Several types of adult stem cells, including mesenchymal stem cells, the multipotent progenitors which yield cells that make up bone, fat, cartilage, and other related tissues, have been found to be remarkable at wound healing. Stem cell scaffolds and grafts would be applied to the wounds, stimulating tissue growth and regeneration for ailments like diabetic foot ulcers.
Immunoprivileging: Stem cell assimilation and treatment of injuries, though, doesn’t have to stay on the surface. One of the incredible things about mesenchymal stem cells is that, when injected into an organism, they tend to migrate towards the locations of greatest need. So, if a patient was recently diagnosed with diabetes, and their immune system is in the process of attacking the beta cells, infused stem cells might naturally move toward the site of inflammation—the pancreas. Once there, the thought is that the stem cells will act in their natural healing capacity, limiting the immune offense and creating an immunopriveleged environment around the beta cells. There are several clinical trials recruiting currently to test this theory.
What Can I Do?
Clearly, stem cells promise a lot to us as diabetics—which leaves me wondering, how do we help stem cell research progress, and what should we do today to make sure we have a cure tomorrow?
Join a clinical trial: If you really want to be on the front lines of stem cell research, making contributions where most needed, join a clinical trial that is seeking to use and prove these new cell therapies. You can search for trials at ClinicalTrials.gov and sign up for email alerts through the JDRF. Trial participants are a crucial and much under-appreciated need in the scientific community.
Bank your baby’s blood: This is a bit more obscure, but I’m going to include it because I really think it’s a good idea. Having a baby? Bank your baby’s umbilical cord blood, which is relatively rich in adult stem cells. This isn’t a diabetes-specific suggestion; these cells can be used as a source of autologous stem cells for your child in the case of cancer and any other number of illnesses. So, for a few thousand dollars, consider it a partial health insurance policy for your baby. Check out the Parent’s Guide to Cord Blood Foundation and the Save the Cord Foundation for more information.
Advocate: There is a lot of grief and misunderstanding about stem cell science, and the voice of the patient advocate is a powerful one in this discussion. It is important to know and respect the arguments against stem cell research (a nice summary is available from EuroStemCell), but also to represent the people who can be healed using this incredibly powerful tool. If you want to get involved, you can contact your local stem cell advocacy group; many of these are state-based (the California Institute for Regenerative Medicine and the New York Stem Cell Foundation, for example). Or, you can contact one of the many national and international organizations dedicated to furthering stem cell research, including the JDRF, the American Diabetes Association, Americans for Cures, and so on.
* As a side note: the general consensus is Yamanaka will win a Nobel for this finding, so keep an eye out.
Karmel Allison is ASweetLife’s science editor and a regular contributor. She writes the blog Where is My Robot Pancreas?