An immune system in a bottle would allow faster and easier production of a flu vaccine

University of Michigan associate professor Nicholas Kotov believes that one day, the cells in those honeycombs can be used to grow spare parts for our bodies, or even an entire artificial immune system in a bottle.

An immune system in a bottle would allow faster and easier production of a flu vaccine, thus preventing another shortage, he said. In addition, the immune system in a bottle will give scientists clues how to design vaccines that activate an immune response to the unchanging part of a flu virus, making yearly vaccinations, quite possibly, unnecessary, Kotov said.

In the paper "Inverted Colloidal Crystals as 3-D Cell Scaffolds," published last month in the journal Langmuir, Kotov's lab in the chemical engineering department and other collaborators introduced a way to build those cell-incubating honeycombs---called scaffolds---so that even though the cells occupy different compartments in the honeycomb, they share the same conditions, just as they would share the same conditions if growing in the body.

Collaborators on the paper include researchers from Oklahoma State University, University of Texas Medial Branch and Stillwater Oklahoma-based Nomadics Inc. Kotov has appointments in the biomedical, materials science and chemical engineering departments.

The research is so important that the Defense Advanced Research Projects Agency (DARPA) has funded a consortium of research institutions for $10 million to grow the immune system in a bottle.

Scientists can study the artificial immune system to see how it reacts to biological hazards and their countermeasures, and use the data to make more effective countermeasures, said Jan Walker, DARPA spokesman.

The birthplace of this artificial immune system is Kotov's three dimensional scaffold, which is comprised of inverted colloidal crystals, also called photonic crystals. Colloidal crystals are hexagonally ordered lattices of highly uniform spherical particles that are packed together. They have a wide range of diameters, from nanometers to micrometers and this versatility is critical for controlling the life cycle of cells and how they change (i.e. differentiation).

Kotov's team didn't use robotics or complicated computer set-ups to make the scaffolds. Instead, they used heat and gel to make a simple mold.

First, they infiltrated the crystal with sol gel. When the gel hardened in the channels between the spheres, scientists heated the crystal to burn away all but the walls left by the hardened gel. What's left is an inverted replica, or a mold, of the crystal.

Historically, scientists cultured cells in plates or dishes where they grow in two-dimensional colonies. But because cells proliferate three dimensionally in the body, it's critical that scientists develop a three-dimensional scaffold for cell cultures so the cells' development can mimic what happens inside us. This is particularly important for differentiation of stem cells into different lineages of immune cells. The inverted colloidal crystal scaffold could stimulate differentiation of human stem cells from blood of adults to functional T and B cells. T and B cells help target and kill foreign invaders.

"The uniformity of the environment affects the way the cells are developing," Kotov said. "This is particularly relevant for stem cells and other cells that can differentiate. These scaffolds offer a very good control over the environment."

The final goal of the DARPA project will be replication of the function of the human bone marrow and thymus. Besides University of Texas Medical Branch and Nomadics Inc., it also includes Harvard University, Massachusetts General Hospital, Scientific Research Laboratory Inc, and Fred Hutchinson Cancer Center. Later, the artificial bone marrow and thymus will be integrated with other elements of the human immune system being developed in the multiuniversity team lead by VaxDesign Inc. The ability of the inverted colloidal crystal scaffolds to control the differentiation process of the cells also opens possibilities in using for treatment of leukemia and other forms of cancer.

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