Introduction: Cell therapies represent a promising alternative treatment for neurodegenerative diseases of the spinal cord, and traumatic spinal cord injury. Cell survival, migration, proliferation and differentiation are intrinsic factors that greatly influence the therapeutic potential of cell therapies. Other factors like local inflammatory and immune response also play an important role. This study analyzed the migration patterns of fetal-derived neural precursors (NPCs) transplanted to the spinal cord of healthy Gottingen minipigs.
Methods: Fifteen female minipigs divided into 3 groups received twenty bilateral 10, 25, and 50-microL intraparenchymal injections of NPCs at a concentration of 10,000 cells/microL. Following 21 days, animals were euthanized, perfused, and spinal cords were harvested for immunohistochemistry. Cell grafts (n=5 per group) in both white matter (WM) and grey matter (GM) were quantitatively assessed in the three-dimensional space using stereological volumetric calculations, and in the two-dimensional space using Image J software to estimate migration distance from the epicenter in the rostro-caudal and transversal planes.
Results: Cell grafts exhibited different migration patterns in each anatomical compartment, regardless of injection volume. Cell grafts found in the WM migrated more in the rostro-caudal plane, whereas cell grafts found in the GM migrated similarly in the rostro-caudal and transversal planes. The 50-microL grafts in the WM were significantly wider (p=0.02) when compared to the 10-microL grafts, but not significantly wider when compared to the 25-microL grafts. Additionally, the total volume of GM occupied by the 25-microL grafts was significantly larger (p=0.02) when compared to the 10-microL grafts, but not significantly smaller when compared to the 50-microL grafts. These results suggest that 25 microL is the optimal injection volume at a cell concentration of 10,000 cells/microL.
Conclusions: Understanding the migration patterns and other dynamics of different cell lines will allow neurosurgeons to ensure accurate delivery and maximize effectiveness of cell therapeutics in the spinal cord.
Patient Care: By understanding the cell dynamics of different cell therapeutics targeting spinal cord diseases, neurosurgeons will be able to determine the best transplantation parameters. By doing so, they would maximize the therapeutic benefit while minimizing the risk of damaging the spinal cord.
Learning Objectives: 1. Cell dynamics have a great impact on the therapeutic potential of cell therapies targeting spinal cord diseases.
2. Cells transplanted into different anatomical compartments of the spinal cord have very distinct migration patterns.
3. Migration patterns of cells transplanted into the spinal cord can be used to determine the optimal injection parameters.