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Controlling the Size of Cell Spheroids Improves Therapeutic Efficacy and Minimizes Risks of Stem Cells for Neurogenic Erectile Dysfunction
17 Pages Posted: 14 Sep 2019
More...Abstract
Background: Intracavernous injection (ICI) of stem cells (SCs) has been demonstrated promsing for neurogenic erectile dysfunction (ED), but unexpected animal death after ICI was frequent and the therapeutic outcomes were inconsistent for unknown reasons. Here, our investigation was focused on whether cell escaping is responsible for attenuated therapeutic efficacy and unexpected animal death and its underlying mechanisms.
Methods: Single-cell suspension of SCs and stem-cell spheroids with suitable size were intracavernously injected at doses of 0.5, 1, 2, or 4 million cells. The cell loss and safty after ICI, erectile function and histopathologic change, etc. were analyzed with multimodality of methods.
Findings: Most free SCs escaped from sponge-like corpus cavernosum (CC) after ICI due to their small size, weakening stem-cell therapeutic efficacy. Worse still, the escaped cells were shown to cause widespread pulmonary embolism (PE), and even death in some animals. Further, it was founded that the limited effect of free SCs may be ascribed to the larger cell clusters which were spontaneously aggregated before ICI and were trapped within CC after ICI. In comparison, cell loss and PE were significantly avoided by transplanting stem-cell spheroids. Importantly, better therapeutic outcomes were detected with less stem cells by ICI of stem-cell spheroids.
Interpretation: Transplantation of size-controlled stem-cell spheroids instead of single-cell suspension for neurogenic ED may be a wiser choice to achieve steady therapeutic outcome and minimize risks for the future clinical application.
Funding Statement: This work was supported by the National Natural Science Foundation of China (81701432) (to Y. Xu).
Declaration of Interests: None of the authors have any relationships/conditions/circumstances that present a potential conflict of interest.
Ethics Approval Statement: All animal procedures were conducted following the guidelines of the Institutional Animal Care and Use Committee of the General Hospital of the People’s Liberation Army (Beijing, China).
Keywords: Erectile dysfunction; Stem cells; Three-dimensional culture; Pulmonary embolism; Intracavernous injection
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