Dr. Neele Heitmann
Biology and Biotechnology

Understanding and overcoming neurofibrosis in multiple sclerosis and its models

In a person with multiple sclerosis (MS), an injury to the brain results in a lesion. These lesions can repair themselves, particularly by generation of new oligodendrocyte cells and the myelin they wrap around nerves. However, this process is hindered by several factors within the lesion itself. One such hindrance may be the accumulation of fibroblast cells in lesions. Information on the arrival and aggregation of fibroblasts in MS lesions is emerging but still sparse. My host Prof. Yong and his group have found that areas within MS-like lesions in preclinical models have a high density of fibroblasts, seemingly forming a scar. Importantly, these scar areas are devoid of new oligodendrocytes. Furthermore, the fibroblasts appear to be closely associated with the immune cells, microglia within lesions, as if they were sustaining one another's activities. During the Gateway Fellowship, I will investigate the involvement of fibroblasts in hindering the repair of myelin by oligodendrocytes in MS lesions. 

Firstly, I will analyze the interactions and spatial occurrence of fibroblasts with oligodendrocytes and microglia in tissue samples containing lesions from people with MS. Here, differences between different types of MS lesions will be distinguished. Specific microglia states that interact with fibroblasts will be identified from mouse model data for further investigations to inhibit these interactions. Finally, I will test a new line of medications to overcome the detrimental effects of scarring caused by fibroblasts and promote lesion repair. This will be achieved by culturing different cell types together to assess their impact on scar formation, repair capacity, oligodendrocyte health, and the inhibition of reciprocal stimulation of microglia. These experiments will pave the way for further testing of the drug candidates in a model for repair later in my postdoctoral research. This research will provide a new understanding of MS neuropathology and carve a new direction in overcoming impediments to repair processes within the brains of people living with MS.