Investigation of endogenous stem cells and reactive astrocytes in post-traumatic syringomyelia
|Institution:||University of New South Wales|
|Department:||Clinical School - Prince of Wales Hospital|
|Keywords:||Syringomyelia; Stem cells; Astrocytes|
|Full text PDF:||http://handle.unsw.edu.au/1959.4/40674|
Introduction: Around a quarter of patients with spinal cord injury develop post traumatic syringomyelia (PTS), causing progressive neurological deficits. Current surgical treatment is unsatisfactory. Endogenous stem cell therapy, aiming at replacing lost tissue and repairing damaged ones by endogenous progenitors, may offer hope. Investigation into the reaction of endogenous progenitors in PTS may extend our knowledge about stem cell biology and help to develop a new treatment option for PTS. Endogenous stem cells were found to differentiate into astrocytes. Reactive astrocytes and gliosis are shown to have an important role in spinal cord injury, such as protecting neurons, limiting inflammation and regulating local environment to suit progenitors. We hypothesize that reactive astrocytes may play an important protective and potential therapeutic roles in PTS. The aim of this thesis is to study proliferation, differentition and location of endogenous progenitors and their roles in PTS. Materials and methods: Excitotoxic injury model of PTS was performed in adult Wistar rats. Proliferating cells were marked by either exogenous mitotic marker bromodeoxyuridine or endogenous mitotic marker Ki67.lmmunofluorescence techniques targeting mitotic markers were used to trace the proliferating cells. Immunofluorescent double staining techniques were used to phenotype the proliferating cells. Results: A large number of endogenous progenitors appear in PTS from 24 hours to at least 8 weeks post injury (PI). They proliferate much faster in PTS than in the control animals. Although less endogenous progenitors are observed after 4 weeks PI, their number is still much higher than that in the control animals. Immediately after injury, progenitors exist mainly in the white matter, but the majority of them shift their position closer to the lesion within 2 days. In the chronic stage, the majority of stem cells are located in and around the lesion site. Endogenous progenitors differentiate into astrocytes but not oligodendrocytes or neurons within 8 weeks. Astrocytes respond to injury by upgrading GFAP (1 day PI), becoming hypertrophic (7 days PI) and forming glial scar (2 weeks PI) in PTS. The development of a glial scar corresponds with the stage of cyst stability or reduction in size. Conclusions: Endogenous progenitors exist in PTS and they respond to injury by proliferating and shifting their position towards the lesion. These studies are important in understanding the endogenous stem cell response to PTS and lay the groundwork for future studies examining stem cell therapy for the condition. Endogenous progenitors in the PTS model differentiate into astrocytes, which help to form the glial scar lining the syrinx. Reactive gliosis may play an important role to seclude the injury site from healthy tissue, prevent a cascading wave of uncontrolled tissue damage and restrict the syrinx enlargement.