Los Angeles, CA October 13th 2014 – A recent paper published in Cell by Melton and colleagues last week attracted public attention as it demonstrated a protocol to effectively generate billions of human insulin-producing cells from human embryonic or induced pluripotent stem cells. This technology spurs hope to be one step closer to a therapy for type I diabetes.The underlying principle of this paper is to use those stem cell-derived insulin-producing islet cells to cure type I diabetes through implantation in patients or to use them as a model system to develop novel therapies.Patients with type I diabetes mellitus lose their own insulin producing cells and have to rely on insulin injections. Transparency market research estimates the current worldwide market for insulin to be ~$20 billion in 2012 and to reach ~$32 billion in 2019, making this a highly attractive market to enter for novel players with disruptive technologies.Islet cell transplantation has been considered a potential cure to diabetes for a while, but a number of challenges persist. For example, patients can receive transplants of cadaveric islet cells to restore insulin responsiveness to blood glucose levels. However, the supply of these cells is rare. One of the major benefits of a cell transplant in contrast to an organ transplant such as a whole pancreas is that it is much less invasive to the patient. Regardless, in both cases, transplant rejection is a major obstacle and needs to be addressed with immune suppressant therapy. As a consequence, two of the key challenges for a therapy using cell transplantation technology have been 1) immune rejection and 2) cell scarcity.Immune rejection: To address immune rejection, scientists have focused their efforts on the development of immunoisolation devices. The purpose of these devices is to isolate the transplant cells from the host’s immune system through a selectively permeable membrane, which allows passing of nutrients, oxygen and insulin, but not of the host’s immune cells.Cell scarcity: The availability of islet cells has been the focus of the research published in the above mentioned report. Melton and colleagues at the Harvard Stem Cell Institute differentiated large numbers of insulin-producing cells from human embryonic stem cells (ESC). Those islet-like cells were phenotypically similar to cadaveric islet cells, and responded to glucose stimuli with insulin secretion at similar concentrations as the cadaveric cells. When transplanted into a mouse model of diabetes, the cells could restore responsiveness to blood glucose and lowered fasting blood glucose levels, which is elevated in diabetes patients.According to Harvard University’s release, the team is now collaborating with Daniel Anderson at MIT, to develop an immunoisolation device to deliver those cells to patients, potentially addressing both key challenges listed above.Interestingly, since the group also showed feasibility of differentiation of human induced pluripotent stem cells into beta cells, the use of immune suppressant therapy might be avoided by using patient-specific induced pluripotent stem cells (iPSC).The promise of using stem cells for therapeutic purposes is that they can potentially be differentiated into any other cell type. However, the creation of ESC from human embryos holds ethical issues that have been widely discussed in public forum debates. In contrast, iPSC can be generated from adult cells such as skin cells by inducing them with stem cell factors to reprogram to the stem cell state. In fact, the 2012 Nobel Prize in physiology or medicine honored Sir John Gurdon and Shinya Yamanaka for this discovery. As a result, future therapies may rely on the use of patient-specific iPSC, which could be repaired for their underlying defect, and transplanted back into the patient.The demonstration of the effective differentiation of iPSC into beta cells by Melton and colleagues brings us one step closer to patient-specific cell transplantation, which would make the need of immune suppressant therapy almost obsolete. However, a number of technical and safety concerns remain to be solved, making this a dream for future diabetes therapies. Until then, delivery of ESC-derived beta cells with immunoisolation devices may be the way to go.Of note, almost coinciding with the discussed publication, the San Diego-based company ViaCyte started a clinical trial to demonstrate safety of their combination product VC-01 delivering their ESC derived pancreatic endoderm cell line PEC-01 through the immunoisolation device Encaptra. Following subcutaneous implantation, the precursor cells are expected to further differentiate into insulin producing beta cells and regulate blood glucose in diabetes patients.The outcome of this trial will be highly anticipated, following Geron’s failed trial, and given ViaCyte’s relatively unique and extensive funding (~$55M in grants) from California’s Stem Cell Agency (CIRM) including $16.6M in September 2014 to expand clinical development of the VC-01 diabetes therapy candidate.It will be interesting to see if the method developed by Melton’s group may be more effective than ViaCyte’s as it is generating more differentiated cells. However, ViaCyte appears to have a solid patent portfolio which might be a challenge to overcome for potential commercial competition.Jeffrey Millman, one of the co-first authors of the Cell paper, comments:“…I think that ViaCyte has a very interesting product. There are many challenges with transitioning from laboratory/preclinical work to clinical trials. We'll simply have to wait and see if it actually works in patients. I hope it works for the sake of patients everywhere.ViaCyte's product and what we have published are really two different transplantation strategies for combating diabetes. I suspect that if ViaCyte had developed the ability to produce functional insulin-producing cells in vitro that can rapidly cure diabetic rodents when they were doing their initial work, they would had focused on those cells rather than their progenitor cells. There are several major advantages of our cells.

1. Our cells can rapidly reverse of diabetes upon transplantation, not needing 3-4 months of in vivo maturation to become functional.
2. It is unknown if the ViaCyte progenitors will mature after transplantation in humans the same way it does in rodents. It is also unknown if the maturation will occur differently in different patient populations (for example, if there are medications that could inhibit maturation). Having an already-functional cell would avoid these maturation issues.
3. Our cells can potentially be used for drug screening. It is highly infeasible to take ViaCyte cells, transplant and mature them, remove them, and then screen for drugs ex vivo…”

We are looking forward to both seeing the results of ViaCyte’s clinical trial and to seeing if the group around Millman and Melton will commercialize their discovery.Should any of the groups be successful, stem cells could really cure diabetes in the near future.Disclaimer: Some of the companies listed above may be DeciBio clients or customersAuthor: Nadia Sellami, Associate at DeciBio Consulting, LLCConnect with Nadia Sellami on Google+https://plus.google.com/117691499321660219577hConnect with Nadia Sellami on Linkedi