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Ouyang et al. Stem Cell Research & Therapy (2018) 9:246 Page 8 of 12

Fig. 5 Transplantations of MSCs or MSC-Exos increase the smooth muscle contents of the corpus cavernosum. a The expressions of SMA in the
corpus cavernosum were detected at 4 weeks in each group. Original magnification, ×200 DAPI = 4′,6-diamidino-2-phenylindole. b Representative
images of Masson trichrome staining of actin and collagen in each group. Smooth muscle and connective tissue in the corpus cavernosum are
stained red and blue, respectively. Original magnification, ×200. c Representative images of western blots for SMA cavernosum in each group. d
Data are presented as the relative density of SMA compared with that of β-actin. The density was determined semiquantitatively using ImageJ.
Each bar depicts the means ± standard deviations from n = 8 animals per group. *p < 0.05 compared with the PBS vehicle group. e Effect of
MSCs or MSC-Exos treatment on the ratio of smooth muscle to collagen in the corpus cavernosum. Bars denote the mean densitometry ratio
between smooth muscle content and collagen content per field (± standard error of the mean). *p < 0.05 compared with the PBS vehicle group

from the culture supernatants of MSCs and observed are involved in tissue repair as paracrine mediators. A
their efficacy in ameliorating CNI-induced ED in rats, as growing number of studies suggest that MSCs and
defined by higher ICP/MAP ratios and nNOS expres- MSC-Exos yield similar therapeutic benefits in various dis-
sion, higher smooth muscle/collagen ratios, as well as re- ease models [23, 35]. It has also been shown that the exo-
duced caspase-3 expression. We also demonstrated in somes released by MSCs can ameliorate diabetes mellitus
vivo and in vitro that MSC-Exos could be internalized (DM)-related ED by anti-fibrotic and anti-apoptotic mecha-
into cavernosum cells and CCSMCs, inhibiting the nisms and increase endothelial and smooth muscle content
caspase-3 dependent apoptosis pathway. [36, 37]. Exosomes-mediated cell-free therapies have many
Exosomes have been demonstrated to be an important advantages compared with cell therapy, including the fol-
mode of cellular communication [20], as they are involved lowing: (i) they have greater stability and are easier to store
in multiple physiologic and pathologic functions, including and manage because exosomes can be stored at − 20 °C for
proliferation [31], apoptosis [32], inflammation [33], and 6 months with no loss of biochemical activity [38], (ii) they
tissue regeneration [34]. MSC-Exos contain growth factors, do not present a risk of tumor formation, and (iii) exo-
signaling lipids, mRNAs, and regulatory miRNAs, which somes are less immunogenic than cells. Thus, exosomes