Combining the cell-encapsulation technique and axon guidance for cell transplantation therapy.

In cell transplantation therapy for the treatment of neurodegenerative disorders, encapsulation of implanted cells in a semipermeable membrane is a promising approach to protect the implanted cells from host immune rejection and inhibit the invasion of tumor into surrounding tissue if the implanted cells form a tumor after transplantation. However, implanted neurons isolated by capsules could not build connections with host neurons, preventing the implanted neurons from responding to stimuli from host neurons. In the present study, we focused on the passage of neurites and axons navigated by axon guidance molecules through membrane pores to enable encapsulated neurons and host neurons to form connections. The type of matrix coated on membranes and the pore size of the membranes greatly affected the successful passage of PC12 neurites through membrane pores. PC12 neurites preferably passed through collagen-coated membranes with pores greater than 0.8 μm in diameter, but the neurites did not pass through albumin- or fibronectin-coated membranes or membranes with pores less than 0.1 μm in diameter. We could navigate the direction of commissural neural axon extensions by utilizing the axon guidance molecules secreted from floor plate and make guided axons pass through the membrane pores. These results suggest the feasibility of building connections between encapsulated neurons and host neurons by encapsulating the implanted neurons and axon guidance molecules, which attract the axons of host neurons into the capsule, in the porous membranes with suitable pore size and matrix coating.