Yesterday I toured the research lab of Dr. Tejal Desai, on the UCSF SoMa campus. Dr. Desai's team is researching islet cell encapsulation, with the eventual goal of implanting "protected" cells into people with diabetes to restore blood sugar auto-regulation. Hey! I want that!
I already knew a wee bit about the idea: you take insulin-producing cells, coat them in plastic (or some such substance) that's specially made to let glucose and oxygen in and insulin out, but not trip the autoimmune attack that created the diabetes to begin with, and voila! you're cured (sort of). This was considered a very exciting prospect about 15 years ago, but fell by the wayside due to a lack of success in identifying a workable coating. Much hope was placed in alginate coatings (yeah, algae), but they degraded quickly when implanted (in animals) and the islet cells died.
Enter Dr. Desai, and this fascinating discovery: cells not only require a particular chemical environment in order to thrive, but also a particular geographical environment.
She described it to me thusly: your body is essentially a system of scaffolding that holds all its cells in place, and the precise shape and structure of that scaffolding in any particular spot affects the growth and activity of the cells housed in that spot.
What's this mean for islet encapsulation? It means that we can't just coat them in goo and inject them someplace, because they need to be housed within a specific extracellular structure in order to do their work. Dr. Desai and her collaborators are figuring out exactly what this structure needs to be.
I got to see and hold some experimental encasements yesterday. They look like tiny metal boxes with reservoirs inside and porous "windows". These windows are actually the porous memberanes through which communication will occur with the extracellular environment. In addition to researching the optimum structure for these encasements, the lab members are also working on how to make these little spaceships clean-outable and refillable, because the cells within will naturally reproduce and die off, eventually running out of space.
In addition to these pursuits here are some more of the questions involved in this research:
- What's the best material to make the "scaffolding" out of? It needs to be porus and soft, but not fragile enough to break apart or degrade in the body.
- How many cells should be implanted, and should they be grouped in any particular way? Insulin-producing cells don't like to be alone, but also don't like to be over-crowded. Further research in the Desai lab is examining the precise number of cells to cluster together for optimal longevity and function.
- What size and shape should the pores in the coating be? The material has to allow some molecules to pass through, while keeping others out. If the "good" ones were small and the "bad" were large then this might be a no-brainer. But of course, it's not nearly that simple. The lab is experimenting with complicated pore shapes that interact differently with different molecules.
Personally, I'm a big fan of the "smart insulin" idea. But seeing the great work that's going on in Dr. Tejal Desai's lab yesterday really jazzed me up about the possibilities of islet cell transplantation. The challenges and questions are extraordinarily complex, but these folks are getting some real answers.
Click here for more information about Dr. Desai and her lab.
