The Potential of Adult Human Bone Marrow-Derived Cells for Repair in Multiple Sclerosis

The ability of the CNS to respond to injury and disease by increasing cell production and attempting repair has only recently been appreciated. However, the inadequate or abortive replacement of cells within the CNS compares poorly with the regeneration and functional repair seen in other organs. The haemopoietic system however, is renowned for the on-going production and maintenance of circulating populations of cells with short life spans. Investigation of this system has informed our knowledge of stem cell biology and led to the development of the traditional stem cell model. This hierarchical paradigm of pr9gressive lineage restriction has recently been challenged by studies suggesting that adult stem cells have greater plasticity (more differentiation choices) than previously appreciated. Of particular relevance to the development of therapeutic interventions for neurological disease is the expression of neuronal or glial markers by cells derived from lineages not previously thought to have neuroectodermal potential. The aim of this work was to explore biological and clinical aspects of the potential of adult bone marrow-derived cells for reparative transplantation therapy in demyelinating disease. In vitro studies have investigated the baseline expression of glial markers in these cells. Via manipulation of culture conditions, the proportion of bone marrow-derived cells expressing neuroepithelial and early glial markers has been increased. Human MSCs (hMSCs) have been shown to migrate in response to chemokines expressed in demyelinated lesions and to support the growth and proliferation of a cell line with many of the characteristics of oligodendrocyte progenitor cells. Some limited studies investigating the in vivo potential of hMSCs for repair in animal models of demyelination have been performed. In view of the known safety profile of bone marrow cell transplantation, a small safety and feasibility study of the autologous, intravenous transplantation of human bone marrow in Multiple Sclerosis patients has been commenced.EThOS - Electronic Theses Online ServiceGBUnited Kingdo