Year 1

The surgical tools currently available to transplant cells to the human brain are crude and underdeveloped. In current clinical trials, a syringe and needle device has been used to inject living cells into the brain. Because cells do not spread through the brain tissue after implantation, multiple brain penetrations (more than ten separate needle insertions in some patients) have been required to distribute cells in the diseased brain region. Every separate brain penetration carries a significant risk of bleeding and brain injury. Furthermore, this approach does not result in effective distribution of cells. Thus, our lack of appropriate surgical tools and techniques for clinical cell transplantation represents a significant roadblock to the treatment of brain diseases with stem cell based therapies. A more ideal device would be one that can distribute cells to large brain areas through a single initial brain penetration.

In this first year of progress, we have designed, prototyped, and tested a stereotactic neurosurgical device capable of delivering cells to a volumetrically large target region through a single cortical brain penetration. We compared the performance of our device to a currently used cell transplantation implement – a 20G cannula with dual side ports. Through a single initial penetration, our device could transplant materials to a region greater than 4 cubic centimeters. Modeling with neurosurgical planning software indicated that our device could distribute cells within the entire human putamen – a target used in Parkinson’s disease trials – via a single transcortical penetration. While reflux of material along the penetration tract was problematic with the 20G cannula, resulting in nearly 80% loss of cell delivery, our device was resistant to reflux. We also innovated an additional system that facilitates small and precise volumes of injection. Both dilute and highly concentrated neural precursor cell populations tolerated transit through the device with high viability and unaffected developmental potential. Our device design is compatible with currently employed frame-based, frameless, and intraoperative MRI stereotactic neurosurgical targeting systems.