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Transplanted Haematopoietic Cells Populate The Murine CNS In The Absence Of Irradiation

Resource type
Thesis type
(Thesis) M.Sc.
Date created
2013-03-08
Authors/Contributors
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.
Document
Identifier
etd7680
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The author granted permission for the file to be printed and for the text to be copied and pasted.
Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Krieger, Charles
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etd7680_JManning.pdf 3.12 MB

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