Page 37 - MSC & Exosomes in autoimmune

Ouyang et al. Stem Cell Research & Therapy (2018) 9:246
https://doi.org/10.1186/s13287-018-1003-1

RESEARCH Open Access

MSC-derived exosomes ameliorate erectile

dysfunction by alleviation of corpus

cavernosum smooth muscle apoptosis in a

rat model of cavernous nerve injury

1† 2† 1 1 2 1*
Xi Ouyang , Xiaoyan Han , Zehong Chen , Jiafeng Fang , Xuna Huang and Hongbo Wei

Abstract
Background: This study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile
function in a rat model of cavernous nerve injury (CNI).
Methods: MSCs were isolated from rat bone marrow and exosomes were isolated from the supernatants by
ultracentrifugation. The tissue explant adherent method was used to isolate and culture corpus cavernosum
smooth muscle cells (CCSMCs). MSCs and CCSMCs were identified by flow cytometry, in vitro differentiation or
immunofluorescence staining. Thirty-two 10-week-old male Sprague Dawley (SD) rats were divided into four
groups: a sham operation group and bilateral CNI groups that received intracavernosal (IC) injection of either
PBS, MSCs or MSC-Exos. Four weeks after CNI and treatment, the erectile function of the rats was measured by
electrically stimulating the cavernous nerve. The penile tissues were harvested for blinded histologic analysis and
western blotting. H 2 O 2 was used to induce apoptosis in the CCSMCs, and a flow cytometer was used to measure
the cell viability of the CCSMCs treated with or without exosomes in vitro.
Results: Recovery of erectile function was observed in the MSC-Exos group. The MSC-Exos treatment significantly
enhanced smooth muscle content and neuronal nitric oxide synthase in the corpus cavernosum. The ratio of
smooth muscle to collagen in the corpus cavernosum was significantly improved in the MSC-Exos treatment
group compared to the PBS vehicle group. WB confirmed these biological changes. Cell viability of the
CCSMCs was increased in the MSC-Exos-treated groups, and caspase-3 expression was decreased after the
MSC-Exos treatment in vivo and in vitro.
Conclusions: Exosomes isolated from MSCs culture supernatants by ultracentrifugation could ameliorate CNI-
induced ED in rats by inhibiting apoptosis in CCSMCs, with similar potency to that observed in the MSCs-
treated group. Therefore, this cell-free therapy has great potential for application in the treatment of CNI-
induced ED for replacing cell therapy.
Keywords: Mesenchymal stem cells, Exosomes, Cavernous nerve injury, Erectile dysfunction, Apoptosis

* Correspondence: drweihb@126.com
†
Xi Ouyang and Xiaoyan Han contributed equally to this work.
1
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun
Yat-sen University, Tianhe Road 600, Guangzhou 510630, China
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.