Cell vs. Chemokine Therapy in a Nonhuman Primate Model of Chronic Intrinsic Urinary Sphincter Deficiency

Mixed efficacy results of autologous skeletal muscle precursor cell (skMPC) therapy for women with chronic intrinsic urinary sphincter deficiency (ISD) has increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 and skMPCs on chronic urinary sphincter regeneration in chronic ISD.

Five million autologous skMPCs, or 100 ng CXCL12, were injected into the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6 months duration) ISD. These treatment groups (n=3/group) were compared to no ISD/no injection (n=3) and ISD/vehicle injection (n=3) groups. Maximal urethral pressures were measured at rest and during stimulation of the urinary sphincter pudendal nerves at baseline and again at 6 months post-treatment. The monkeys were then necropsied and urinary sphincters collected for tissue analysis of muscle and collagen content, vascularization and motor endplates.

CXCL12, but not skMPC, increased resting MUP in NHPs with chronic ISD (p>0.05 vs. ISD/vehicle injection). skPMCs and CXCL12 only partially restored pudendal nerve-stimulated increases in MUP (p>0.05); sphincter vascularization and motor endplate expression in chronic ISD. Additionally, CXCL12, but not skMPC injections, decreased collagen and increased muscle content of urinary sphincter complex in monkeys with chronic ISD (p<0.05 vs. ISD/vehicle injection; p>0.05 vs. no ISD/no injection).

Results raise questions about cell therapy for chronic ISD and identify a chemokine treatment (CXCL12) as a potential alternative for the treatment of chronic ISD.

The Journal of urology. 2016 Jun 04 [Epub ahead of print]

J Koudy Williams, Ashley Dean, Sherif Badra, Shannon Lankford, Kimberly Poppante, Gopal Badlani, Karl-Erik Andersson

Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC. Electronic address: ., Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC., Urology Department, Ain-Shams University Hospitals, Cairo, Egypt., Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC., Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC., Wake Forest University Baptist Medical Center, Department of Urology., Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC; Institute for Clinical Sciences, Department of Obstetrics and Gynecology, Aarhus University, Aarhus Denmark.