Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury

BackgroundThis study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.Methods and resultsMale adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720 degrees counterclockwise for 2h, then detorsion (i.e., reperfusion) to the original position for 72h], group 3 (TTIR + Mel/intraperitoneal administration/50mg/kg at 30min after ischemia, followed by 20mg at 3h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 x 10(6) cells/by tail-vein administration at 30min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ss /Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, -tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001).ConclusionMel-ADMSCs effectively protected the testis against TTIR injury.

Automated summary

The combined use of melatonin and adipose-derived mesenchymal stem cells effectively protects the testis against acute testicular torsion-induced ischemia-reperfusion injury.