The role of amphoterin-induced gene and open reading frame (AMIGO) family in myelination and neurodegeneration and Investigating the roles of mesenchymal and hematopoietic stem cell conditioned media on neutrophil recruitment in a model of inflammation

Tickle, Joseph (2013). The role of amphoterin-induced gene and open reading frame (AMIGO) family in myelination and neurodegeneration and Investigating the roles of mesenchymal and hematopoietic stem cell conditioned media on neutrophil recruitment in a model of inflammation. University of Birmingham. M.Res.

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Abstract

Project 1: Myelination plays a key role in both the developing CNS and repair from neurodegenerative diseases such as multiple sclerosis (MS). Previous work has suggested a role for the amphoterin-induced gene and open reading frame (AMIGO) family of proteins in this process. Data shown here proposes a novel role for the AMIGOs in both the developmental and repair processes of myelination. Immunofluorescent staining showed AMIGO expression in the developing mouse brain in a similar, progressive pattern to myelination. AMIGO expression was also found in oligodendrocyte precursor cells (OPCs), oligodendrocytes and astrocytes in the spinal cord during experimental autoimmune encephalomyelitis (EAE). These cells are either myelinating or have myelination-regulating function. These combined results suggest a role for the AMIGOs as potential positive regulators of myelination.

Project 2: Evidence suggests that both mesenchymal and hematopoietic stem cells (MSCs and HSCs) can alter an inflammatory environment in vivo by secretion of inflammation-modulating agents. This was examined by first developing an in vitro model of inflammation. Addition of MSC and HSC conditioned media increased Kc-activated neutrophil adhesion to TNF-α-activated colon and renal endothelium, respectively. This increase in adhesion was enhanced by pre-stimulation of SCs with cytokines and chemokines, particularly H2O2 and TNF-α. Similarly, treatment with different SC-conditioned media altered the adhesion of activated neutrophils to VCAM-1, ICAM-1, MAdCAM1 and hyaluronan. This effect was further manipulated by treatment of SCs with cytokines and chemokines, particularly H2O2, TNF-α and IFN-γ. This data suggest that MSCs and HSCs potentially have multiple effects on the inflammatory site

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):