Stem Cells for Neurovascular Erectile Dysfunction
[um_loggedin show_lock=yes]Authors: Cara A. Clouse, DVM
Affiliations: Wake Forest Institute for Regenerative Medicine
Introduction: Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection that is sufficient for sexual intercourse. In equine theriogenology, ED is most commonly seen in stallions that are inexperienced or subject to mismanagement. A separate, targeted population experiences ED secondary to neural, vascular and/or musculoskeletal defects. These lesions remain difficult to treat despite advances in pharmacotherapeutic and management approaches. Cell-based therapies have received increasing attention regarding their potential for recovering erectile function in the human patient populations. There is now the potential of similar therapies being developed for veterinary demographics.
Hypothesis/Objectives: The goal of this study is to determine whether stem cells implanted into the corpora cavernosa could improve erectile function and restore histological structure in a rat model of neurovascular erectile dysfunction (NVED). This therapy could then be further developed for translation for use in different species.
Materials and Methods: The NVED model was established in an athymic rat (13-15 weeks old) by crushing the bilateral cavernous nerves and ligation of the bilateral internal pudendal bundles. Different types of human stem cells and conditioned media derived from human stem cells were used. The injection of normal saline acted as control. Stem cells were injected into the corpora cavernosa directly after the model was created. Erectile function and histology of the penile tissue were assessed 12 weeks after stem cell injection. Multiple groups were compared using one-way ANOVA. Statistical significance was set at p < 0.05. Results: The ratio of intracavernous pressure to mean arterial pressure was increased in groups 12 weeks after stem cell-based treatment, compared to a saline control group. Amniotic fluid-derived cells (AFSCs), placental-derived cells (PSCs), and endothelial cells (EC) injection showed significant improvement in intracavernous pressure (P <0.05). This recovery was most profound when AFSCs were injected. Functional recovery with PSCs appears greatest at 6 weeks but continues to be observed even out to 12 weeks. Immunofluorescence staining displayed more cells expressing biomarkers of endothelial, smooth muscle, and nerve cells within the corpora cavernosa compared to the saline injection group. Conclusions: All studied cell types provided some degree of functional recovery in rats that were subjected to the NVED. Histologic evaluation confirms regeneration of endothelial, smooth muscle and neural cells following cell administration. Conditioned media derived from PSCs provides partial recovery. Stem cell-based therapy enhanced erectile function and ameliorated the histological structural changes observed in NVED rats. This indicates that stem cell-based therapy may induce vascular, myogenic and neurogenic tissue regeneration in a rat model of severe erectile dysfunction. Future directions would be to determine homologous cell types for veterinary patients and further development of a cell-free alternative using conditioned media.
Acknowledgements, Funding, and Conflicts of Interest: This is work was supported by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
Acknowledgments go to members of the Jackson Lab, the Marini Lab, and collaborators Drs. Ryan Terlecki, Yuanyuan Zhang, James Yoo, Anthony Atala, and Tom Lue
Technical support by: Douglas Schankle, Anna Young, Melissa Ayers
We would like to thank the Regenerative Medicine Clinical Center for the supply and characterization of multiple cell lines (PSCs and AFSCs)
No conflicts of interest to declare.
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