Abstract
METHODS: ISD was created in female NHPs by cutting and then cauterizing the pudendal innervation to the urinary sphincter complex. Chronic fibrotic, muscle poor ISD developed within 6 months post-surgery. Partial bone marrow transplantation with autologous Lenti-GFP bone marrow cells (BMCs) was performed and NHPs (n1⁄46/ experimental condition) were then given sphincter injections of LentiMcherry-labeled 5 million autologous skMPCs, or SDF-1a. Tissues were removed 6 months later and analyzed for sphincter content of muscle, collagen, BMCs, skMPCs and SDF-1a. RESULTS: When compared to previously studied NHPs with acute ISD (Badra et al, J Urol. 2013;190(5):1938), there was less expression of BMCs andSDF-1a in the urinary sphincter complexes ofNHPswith chronic ISD (p<0.05). This correlated with reduced effectiveness of skMPCs to restore sphincter muscle, innervation and vascularization in chronic vs. almost complete restoration in acute ISD (p<0.05). That injection of SDF-1a restores sphincter structure and function in chronic ISD further supports a role of the SDF-1a pathway in sphincter regeneration. CONCLUSIONS: The underlying reason(s) by which SDF-1a can, but skMPC cannot, stimulate sphincter regeneration in chronic ISD remains unclear, but could be related to the reduced capacity of skMPCs to stimulate SDF-1a mediated cell homing to the sphincter complex in chronic ISD. Providing SDF-1a to a fibrotic urinary sphincter may represent a novel approach to treat chronic ISD.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call