Helmets for hormones

In science, sometimes small things create big problems.

While doctors have been transplanting whole organs for years, they have yet to figure out a way to transplant only a few cells, which would allow them to implant proteins and hormones like kidneys and livers.

One of the problems with cellular transplantation, however, is finding an appropriate ‘container’ in which to place to protect them from the body’s immune system.

A University of Massachusetts researcher has an idea.

If Anthony Dinsmore, an assistant professor of physics at UMass Amherst, can figure out how to package the cells in tiny particles called colloids, the technology could allow doctors to, among other things, transplant islet cells that produce insulin into diabetic patients, rendering insulin shots unnecessary.

Dinsmore and an international team of researchers have proposed a method of encapsulating living cells using colloids, which are particles smaller than their surrounding particles. When colloids are placed in a liquid, they remain suspended rather than sinking to the bottom.

But in order to work, the team’s capsules have to meet certain requirements. First, it has to have pores of specific sizes that would serve as a selective barrier, allowing the cell’s basic functions to continue uninterrupted, Dinsmore said. According to Dinsmore, food, oxygen and water should be able to move into the cell, while hormones and waste products should manage to travel out.

Another requirement is the capsule should be made of a substance that the body will accept, preventing the body’s immune system from successfully launching an attack against the enclosed cells, he said.

So, Dinsmore’s team turned to colloids.

To build the capsules, the scientists used two liquids that do not mix, such as oil and water. When a drop of water is added to oil containing colloidal particles, the colloidal particles immediately surround the water droplet to reduce the total surface energy. The spaces between the spherical colloidal particles form uniform pores with adjustable sizes.

Dinsmore calls these capsules colloidosomes.

Joyce Wong, a researcher at the biomedical engineering department at BU, described Dinsmore’s work as ‘a very interesting, very clever method of using self-assembly to encapsulate materials.’

Wong’s research takes the idea of encapsulation and drug delivery one step further. While Dinsmore’s work creates the capsules, Wong is trying to ‘decorate them,’ or attach molecular markers onto these capsules that will be able to find specific regions of a blood vessel, like those with an atherosclerotic plaque. These sorts of methods will be crucial for early detection and prevention of disease, Wong said.

But before the capsules can be decorated, they need to be strong.

When first assembled, Dinsmore’s capsules are not stable enough to be moved around. But they can be stabilized by heating the solution, which makes the particles coalesce and form little bridges between one another. These stable colloidosomes can then be centrifuged, removed from the oil and placed in water to allow diffusion through the capsule.

Other methods of encapsulation have been proposed, but Dinsmore said using colloidosomes has several advantages.

‘Colloidosome sizes are well controlled, and pore sizes are well controlled,’ he said. The better control, he said, allows researchers to design and create exactly the sort of capsule that they want.

Another important feature of colloidosomes is that they are self-assembling, he said. The capsules form as soon as the appropriate ingredients are in the solution, allowing the researchers to make many capsules at the same time with a wide variety of inner core cell materials.

In case the materials within the capsule need to be released, the colloidosomes can be ruptured, Dinsmore said. If the capsules are made of a material that swells when the pH changes, for example, he said the capsule would burst and release its inner cells when the pH changed.

Also, the capsules could be made of substances that dissolve when they come into contact with certain materials, he said.

The researchers successfully packaged fibroblast cells, which make connective tissue in the body, in capsules that remained alive for several hours. But further work still must be done before these capsules will be ready for delivery into the human body. The fibroblast cells were human, but they weren’t implanted into anyone because the technology to do that hasn’t yet been devised.