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.
The aim of this study was to develop delivery systems for administration of CSF-1 to remedy the systemic deficiency of this cytokine in osteopetrotic op/op mice 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 homozygous op/op mice 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 experiments in 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.
Maysinger
D
D
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Berezovskaya
O
O
Fedoroff
S
S
D000818:Animals; D001704:Biopolymers; D001921:Brain / Q000187:drug effects*; D002214:Capsules; D002452:Cell Count; D002460:Cell Line / Q000648:ultrastructure; D002470:Cell Survival; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008863:Microspheres; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D010022:Osteopetrosis / Q000235:genetics; D011994:Recombinant Proteins
D001704:Biopolymers; D002214:Capsules; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor