Treatment of stress urinary incontinence in rats with umbilical cord mesenchymal stem cells
Objective To investigate the possible molecular mechanism of stress urinary inconti-nence(SUI)induced by simulated labor injury in rats treated by transurethral injection of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods Totally,12 specific pathogen free(SPF)-grade fe-male Sprague-Dawley rats(6 weeks old,145-185 g)were selected and divided into stem cell injection group,saline injection group and blank control group by a random number table method,with 5,4 and 3 rats,respectively.Multiple vaginal balloon dilation(MVD)was used to simulate the birth injury in the stem cell injection group and the saline injection group.After the two injuries,stem cells(2 × 106/piece,250 μl injection volume)and the equivalent amount of saline(250 μl)were given paraurethral injection,respectively.The index changes of leakage point pressure(LPP)and maximum bladder volume(MBC)were detected immediately,9 d and 16 d after MVD in the three groups,respectively.Urethral tissue of rats was extracted,part of it was prepared by paraffin and stained with hematoxylin-eosin to observe the pathological changes of urethral tissue,and part of it was preserved in liquid nitrogen at-80 ℃ for RNA extraction and RNA sequencing.Independent sample t test was used for comparison among the three groups,and one-way analysis of variance was used for comparison within the three groups.Results LPP in stem cell injection group was higher than that in normal saline injection group immediately,9 d and 16 d after surgery[Immediately after surgery:(22.00±1.64)mmHg vs.(20.00±2.09)mmHg,t=22.900,P＜0.05;9 d after surgery:(29.36±3.90)mmHg vs.(26.8±3.88)mmHg,t=15.030,P＜0.01;16 d after surgery:(43.20±7.98)mmHg vs.(24.50±0.98)mmHg,t=6.558,P＜0.05,1 mmHg=0.133 kPa].The MBC of the stem cell injection group was similar to that of the normal saline group imme-diately after surgery[(0.58±0.33)ml vs.(0.58±0.27)ml,t=3.733,P＞0.05],and that of the stem cell injection group was higher than that of the normal saline injection group at 9 d and 16 d after surgery[9 d after surgery:(0.77±0.14)ml vs.(0.74±0.19)ml,t=8.655,P＜0.05;16 d after surgery:(0.83±0.34)ml vs.(0.53±0.09)ml,t=4.212,P＜0.05].Compared with the control group and the sa-line group,the stem-cell injection group had obvious changes in histology and pathology.The main manifes-tations were more smooth muscle,more regular arrangement,and some new muscle fibers.RNA sequencing results showed that there were significant differences in mRNA expression between the stem cell injection group,the control group and the saline injection group,and these differential genes played a role in muscle contraction regulation,angiogenesis,collagen fiber regulation and other aspects.Conclusion Paraurethral injection of hUC-MSCs can improve stress incontinence in rats,which may be closely related to Wnt/aden-osine monophosphate-activated protein kinase(AMPK)/mitogen-activated protein kinase(MAPK)/insulin-like signaling pathway,angiogenesis and collagen fiber regulation.
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