Intravenously engrafted human multilineage‐differentiating stress‐enduring (Muse) cells rescue erectile function after rat cavernous nerve injury

Abstract

ObjectiveTo evaluate the effect of intravenous administration of human multilineage‐differentiating stress‐enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant.Materials and MethodsMale Sprague–Dawley rats were randomised into three groups after CN crush injury. Either human‐Muse cells, non‐Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non‐Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C‐X‐C motif chemokine ligand (Cxcl12) and glial cell line‐derived neurotrophic factor (Gdnf) in the MPG were examined by real‐time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one‐way analysis of variance followed by the Tukey test for parametric data and Kruskal–Wallis test followed by the Dunn–Bonferroni test for non‐parametric data.ResultsThe mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non‐Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non‐Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non‐Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion.ConclusionIntravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.