The Hematopoietic Cytokine Colony Stimulating Factor 1 Is Also a Growth Factor in the CNS: (II) Microencapsulated CSF-1 and LM-10 Cells as Delivery Systems

Abstract

The aim of this study was to develop delivery systems for administration of CSF-1 to remedy the systemic deficiency of this cytokine in osteopetroticop/opmice and to study the microglial response and neuronal survival in op/op mice following cerebral cortex ischemic lesion. Unilateral cerebral cortex ischemic lesions were produced in homozygousop/opmice and either microencapsulated rhCSF-1 or LM-10 fibroblast-like cells producing CSF-1 were administered either locally, at the site and time of the lesioning, or into the peritoneum 2 weeks before the lesion was made. Physical properties (shape, size, integrity) and kinetics of rhCSF-1 release were assessed prior to the experimentsin situ.Depending on the characteristics of the biodegradable polymer (e.g., chitosan with different densities or poly-l-lactic-poly-glycolic acid), remarkable differences in survival of encapsulated cells were observed. Cellular integrity following encapsulation and metabolic activity was regularly assessed for a period of 1 month. The best level of viability was achieved with highly viscous chitosan (311). The results from these studies demonstrate that: (1) rhCSF-1 incorporated into biodegradable spheres can be released and retain its biological activity; (2) microencapsulated LM-10 cells which produce CSF-1 can survive and constitutively release CSF-1 in alginate-chitosan spheres for different lengths of time depending on the physical properties of the chitosan used; and (3) CSF-1 is an important growth factor in the central nervous system where it can both strongly alter morphological changes of microglia and enhance survival of neurons in injured brain.