Cell replacement therapy, in which cells from a donor are injected into a patient's body, has greatly advanced in recent years. In particular, it may now be possible to transplant islet cells into patients with type-I diabetes so that they can secrete insulin properly again in response to varying glucose concentrations in the bloodstream.

Islets, or Islets of Langerhans as they are formally called, are clusters of cells, with each islet containing 3000 to 4000 cells. There are an estimated one million islets in a healthy, adult pancreas and within each islet are several types of cells that work together to regulate blood sugar. The beta cell, for example, senses glucose in the blood and releases the necessary amount of insulin to maintain normal blood sugar levels. Type-I diabetes occurs when the immune system incorrectly sees these cells as potentially dangerous and destroys them.

When these cells are lost, the body can no longer produce insulin (the hormone needed to convert food into energy).

Overcoming donor islet rejection

There are two important problems to overcome in islet transplantation, that is, taking healthy islets from a donor pancreas and transplanting them into patients with diabetes. The first is donor shortage – human islets are in short supply. Second, patients need to be treated with immuno-suppressing drugs during their treatment (which can last a lifetime), so that they do not reject the donor cells. These drugs increase the risk of organ damage and infections.

The first problem could be overcome, in principle, by making use of stem cell-derived-cells. The second is more difficult to deal with, but cell encapsulation could be a potential solution here, say Tejal Desai and colleagues.

Flexible thin film device

Encapsulated cells must remain active and continue to respond to stimuli from their environment – such as changing glucose levels, as is the case in this work. They must also be accepted by the body and not considered as a foreign entity.

To this end, Desai's team made their cell encapsulation devices from polycaprolactone (PCL) thin films. PCL is a FDA-approved biomedical material. "Two films sandwich the cells, encapsulating them between the membranes," explains team member Crystal Nyitray. "The membranes contain micro- and nano-pores and we made them using various templating techniques that allow us to make flexible thin films whose thickness and porosity we can control."

In this study, the researchers used cells from the MIN6 cell line as a model for islet beta cells. MIN6 is a well-established mouse insulinoma cell line known to secrete insulin when exposed to glucose.

The researchers found that the encapsulated cells they studied indeed produced insulin in response to glucose. The devices also failed to produce a foreign-body reaction.

And that was not all: they also induced blood vessel growth in tissue without complications (such as fibrosis). This vascularization allows nutrients to be exchanged between the encapsulated cells and their surroundings.

No need for immune-suppressing drugs

"We are very excited about these results for future applications in cell-based therapeutics," Nyitray told our sister site nanotechweb.org. "And, since our device protected cells from immune-mediated death, we are optimistic that these devices could be employed without the need for immune-suppressing drugs."

The UCSF team says that it now busy looking at how these devices could be implanted with pluripotent stem cell-derived beta cells in diabetic mouse models to overcome insulin dependence. "Given the nature of these thin-film cell-encapsulation devices, future models could be scaled for humans as alternative treatments for type-I diabetes," says Nyitray.

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