Leiden University Scholarly Publications

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Ritfeld, G.J. (2014)

Bone marrow stromal cell : mediated neuroprotection for spinal cord repair

Doctoral Thesis
Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic factors, enabling neuroprotection/tissue sparing in a rat model of spinal cord injury. In this model system, bone marrow stromal cell-mediated tissue sparing leads to motor and sensory function improvements. Moreover, we show that BMSCs__ neuroprotective ability can be enhanced by genetically modifying the cells to overexpress brain-derived neurotrophic factor. However, survival of BMSCs in the injured spinal cord is poor and limits their repair capacity. We investigated the effect of three immunosuppressig agents, Minocycline, Methylprednisolone and Cyclosporine, on macrophage suppression and BMSC survival. All three d rugs effectively reduced the macrophage response, without improving...Show moreCurrently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic factors, enabling neuroprotection/tissue sparing in a rat model of spinal cord injury. In this model system, bone marrow stromal cell-mediated tissue sparing leads to motor and sensory function improvements. Moreover, we show that BMSCs__ neuroprotective ability can be enhanced by genetically modifying the cells to overexpress brain-derived neurotrophic factor. However, survival of BMSCs in the injured spinal cord is poor and limits their repair capacity. We investigated the effect of three immunosuppressig agents, Minocycline, Methylprednisolone and Cyclosporine, on macrophage suppression and BMSC survival. All three d rugs effectively reduced the macrophage response, without improving transplanted BMSC survival. Transplanting the cells within the reverse thermal gel ESHU, did significantly improve BMSC survival which was associated with increased tissue sparing and improved functional recovery. These effects are likely due to ESHU__s anti-oxidative properties. Future research will need to focus on combinations of neuroprotective BMSC transplants with axonal regenerating promoting therapies to further optimize BMSC-based therapy for spinal cord injury.Show less
ESHU
Immunosuppression
BDNF
Locomotion
Transplantation
Spinal cord injury
Neuroprotection
BMSC
All authors
Ritfeld, G.J.
Supervisor
Roos, R.A.C.
Co-supervisor
Oudega, M.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2014-02-27
Publisher
Department of Neurology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
ISBN (print)
9789090280646