Year: 2013
Type: article
Abstract: Currently, there are no effective treatments available for patients suffering from amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons.Experiments in rodents and humans with neurodegenerative diseases have shown that after bone marrow transplantation following irradiation-induced myeloablation, donor cells can be found in the central nervous system (CNS).Previous work indicates that irradiation itself may be essential for bone marrow-derived cell (BMDC) entry into the CNS.Here we attempted to determine whether myelosuppressive regimens other than irradiation will potentiate BMDC accumulation in the CNS.Transgenic mice over-expressing human mutant superoxide dismutase-1 (mSOD) develop motor neuron loss resembling amyotrophic lateral sclerosis (ALS).We treated control and mSOD mice with the chemotherapeutic agent, Busulfex (BU), and transplanted with GFP + BM.Sub-myeloablative doses of 60-100 mg/kg BU induced ≥80% blood chimerism in these animals.In addition, GFP + cells were observed in the spinal cords of both control and mSOD mice.Greater numbers of GFP + cells were detected in mSOD spinal cords at disease end-stage compared to controls.Histological analysis of BMDCs revealed that a large fraction of donor cells acquired the stellate morphology and immunophenotype characteristic of parenchymal microglia.These data demonstrate that BU alone can be used to achieve high level BM chimerism in mice and lead to accumulation of BMDCs in the spinal cord.These protocols could be adapted for use in humans with neurodegenerative diseases such as ALS.
Source: Summit (Simon Fraser University)
Author: John Manning
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W117782916