Bone marrow stromal cells stimulate neurite outgrowth over neural proteoglycans (CSPG), myelin associated glycoprotein and Nogo-A
Section snippets
Materials and methods
Primary bone marrow stromal cell (MSC) culture. Following local research ethical committee approval and informed consent, bone marrow aspirates were harvested from the iliac crest of individuals with a complete long-term SCI (n = 8; 3+ months post injury, ages 23–66) or from non SCI-patients undergoing spinal fusion in the treatment of low back pain (n = 4; ages 32–54). Mononuclear cells isolated by density gradient centrifugation (Lymphoprep, Fresenius Kabi Norge, AS) were plated out in Dulbecco’s
MSC promote DRG neurite outgrowth and extension over CSPG
In the absence of MSC, DRG neurites were repelled by CSPG in a concentration-dependent manner, as has been reported previously [34], [35], [41]. Thus, at relatively high CSPG concentrations (10–100 μg/ml), DRG neurites either stopped elongating at the collagen: CSPG boundary or they turned and subsequently elongated along the boundary, whilst at lower concentrations (0.1–1 μg/ml), DRG neurites continued to extend and cross over the CSPG. In marked contrast, in MSC/DRG co-cultures DRG neurites
Discussion
Human MSC transplantation has been shown to promote axonal regeneration and functional recovery in animal models of CNS damage, particularly following injury to the spinal cord [9], [10], [12], [14], [15]. Few experiments, however, have addressed how MSC are involved in this process. To investigate potential mechanisms, we have examined how human MSC and neurons interact in the absence and presence of extracellular molecules that are considered to be potent inhibitors of axonal regeneration. We
Acknowledgments
We are grateful to all participants in this study. This study was funded in part by the Institute of Orthopaedics, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.
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