Research

Pluripotent stem cells have the unique capacity to replicate indefinitely and to differentiate into all cell types in the body. The challenge of the past several decades has been identifying the processes and signaling pathways necessary to direct that differentiation into specific cell types, like pancreatic beta cells. Semma’s science is focused on bringing the promise of stem cells to patients through generating billions of stem cell-derived pancreatic beta cells in combination with a state-of-the-art cell delivery technology.

The pancreas normally differentiates from the endodermal germ layer, and early research in generating pancreatic tissues from stem cells mimicked the step-wise developmental signals observed in model organisms. This work led to the successful generation of stem cell-derived definitive endoderm and pancreatic progenitor tissue. However, the biggest hurdle has remained—differentiating human pancreatic progenitors into fully functional insulin-secreting beta cells in vitro.


Image source: Pagliuca and Melton, 2013

In a major scientific breakthrough, scientists in Dr. Douglas Melton’s lab at the Harvard Stem Cell Institute achieved the long-awaited feat of generating beta cells in a dish. Scientists investigated hundreds of combinations of temporally dynamic protein signals, small molecules, and cell culture conditions to develop a multi-stage process that generates functional beta cells in a dish.


Image source: Pagliuca et al., 2014

These stem cell-derived beta (SCbeta) cells were rigorously tested in vitro and in vivo to demonstrate comparability to beta cells within human islets. When challenged repeatedly with glucose in vitro to mimic changing blood glucose conditions in the body, SCbeta cells responded to increased glucose by secreting increased insulin. This pattern of behavior mimics the key functional feature of endogenous human beta cells. SCbeta cells also show similar gene and protein expression to human beta cells, and contain crystallized insulin secretory granules


Image source: Pagliuca et al., 2014

Unlike pancreatic progenitors or previously reported insulin-expressing cells, SCbeta cells function in vivo immediately post-transplantation. Early pre-clinical work has demonstrated that mice transplanted with human SCbeta cells show high levels of human insulin their blood after a glucose challenge. Importantly, when transplanted into multiple animal models of diabetes, SCbeta cells can effectively control the disease, setting the stage for bringing this technology to the clinic.


Image source: Pagliuca et al., 2014

Semma is building on the scientific foundation laid by this work and its scientific team continues to innovate in order to bring the best beta cell product to diabetic patients. In parallel, Semma scientists and engineers are developing state-of-the-art cell protection and delivery strategies for clinical transplantation of these remarkable cells.


Image source: Pagliuca et al., 2014