Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction
Authors: Fang Jia-feng , Huang Xu-na , Han Xiao-yan , Ouyang Xi , Fan Lei , Zhao Xin , Chen Ze-hong , Wei Hong-bo 
Published: March 2018

Abstract

Background
Whether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown.

Aim
To investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI).

Methods
MSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Outcomes
Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed.

Results
MSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs.

Clinical Translation
Combined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models.

Strengths and Limitations
The study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition.

Conclusion
Combined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs.