Transplantation of adult neural stem/progenitor cells and bone marrow derived mesenchymal stromal cells in the injured adult rat spinal cord
Year: 2007
Type: dissertation
Abstract: Neural stem/progenitor cells (NSPCs) have previously been identified in both the mammalian brain and spinal cord. They have the ability to self-renew and are multipotential for both neurons and glia. It has been suggested that they can be used to repair the spinal cord by generating cells useful for repair and an environment that would promote axonal regeneration. It has also been suggested that transplantation of bone marrow-derived mesenchymal stromal cells (BMSCs) into the injured spinal cord may provide therapeutic benefit. We show here that transplantation of adult rat neural stem/progenitor cells (NSPCs) into the injured spinal cord results in mainly glial differentiation of the transplanted cells but poor long term survival. NSPCs have better survival if transplanted rostral and caudal to the lesion, when transplanted in a delayed fashion at 9 days, and if high dose (20 mg/kg/day) cyclosporine is used. In contrast, bone marrow derived mesenchymal stromal cells (BMSCs) survive well and form a bridge across the lesion cavity, but do not differentiate into cells of neural lineage. We were unable to demonstrate functional improvement after transplantation of either NSPCs or BMSCs after 35g clip compression injury. We also transplanted both cell types alone and in combination into a 27g clip injury model. We hypothesized that BMSCs would form a scaffold upon which NSPCs could be seeded, to improve survival of the NSPCs, and improve functional recovery. This study demonstrated that this strategy of sequential transplantation of BMSCs and NSPCs trends toward improved cell survival of the NSPCs, but does not lead to improved functional recovery. However, we did find a significant improvement in functional recovery in rats receiving spinal cord derived NSPCs (SC-NSPCs) only in this 27g clip injury model. NSPCs differentiated mainly into oligodendrocytes and astrocytes, and were seen enveloping non-myelinated axons. The early recovery seen in these experiments, along with the increase in host oligodendrocytes at 7 days, is supportive of a neuroprotective action of SC-NSPCs. A retrograde tracer analysis indicates that SC-NSPC transplantation contributed to either axonal preservation or regeneration, and that the BMSCs did not.
Source: TSpace (University of Toronto)
Author: Parr, Ann Margaret
Institution: University of Toronto
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7132982344