| Part one Rhesus macaque as animal model of pelvic organ prolapseObjective:To evaluate rhesus macaque as animal model of pelvic organ prolapse(POP).Methods:(1)Spontaneous POP rate in rhesus macaques:73 multiparous aged rhesus macaques were included.After anesthesia,Crede's maneuver was used to mimic Valsalva,and the POP-Q of rhesus macaques was recorded according to human POP-Q to evaluate whether rhesus macaques had spontaneous POP.In this study,there were three POP diagnostic criteria:Aa or Ba?0;C or D?0;Ap or Bp? 0.The diagnosis could be made if one of the criteria was met.(2)Changes of vaginal tissue in POP rhesus macaques:four spontaneous POP rhesus macaques were included as POP group,and five age and weight matched rhesus macaques without POP were included as control group.The contents of collagen,elastin and smooth muscle in vaginal tissue were evaluated by histological and biochemical analyses.Results:(1)Among 73 rhesus macaques,11 of them had spontaneous POP,and POP rate was 15.1%.(2)Similar to humans,the vaginal wall of rhesus macaques comprises the following layers:the epithelium,lamina propria,muscularis,and adventitia.(3)Compared with the control group,the ratio of collagen ? and collagen ? in the lamina propria of vagina was significantly decreased in POP rhesus macaques(2.57±0.44 vs 1.63±0.18,P=0.009).(4)Compared with the control group,the elastin content in the lamina propria of vagina in POP rhesus macaques was significantly decreased(12.2 ± 2.3%vs 7.5±1.3%,P=0.015).(5)Compared with the control group,the smooth muscle bundles in the POP group appeared to be disorganized and smaller and the content of smooth muscle was significantly decreased(23.1 ±2.2%vs 18.21±1.70%,P=0.014).Conclusions:(1)Rhesus macaques had spontaneous POP,and POP rate was 15.1%.(2)The vaginal wall of rhesus macaques was similar to that of humans.(3)The change of vaginal wall tissue structure in POP rhesus macaques was similar to that of humans.(4)Rhesus macaque is an ideal animal model for studying POP,given their similarity to humans.Part two Human umbilical cord mesenchymal stem cell transplantation for vaginal repair in an ovariectomized rhesus macaque modelObjective:To evaluate whether human umbilical cord mesenchymal stem cell(HUMSC)therapy can repair vaginal tissue in an ovariectomized rhesus macaque model.Methods:A bilateral ovariectomy model was established in rhesus macaques to induce menopause-related vaginal injury.Ten bilaterally ovariectomized rhesus macaques were divided into two groups(n=5/group):the saline group and the HUMSC group.Three months after ovariectomy,saline or HUMSCs were injected in situ into the injured vaginal wall.The vaginal tissue was harvested after 12 weeks injection for histological and biochemical analyses to evaluate changes of extracellular matrix,microvascular density and smooth muscle in the vaginal tissue.Biomechanical properties of the vaginal tissue were assessed by uniaxial tensile testing.Results:(1)Compared with the saline group,the ratio of collagen I in the lamina propria was significantly increased(6.9±1.7%vs 14.5±3.7%,P=0.006)and that the ratio of collagen ? was significantly decreased(8.3 ± 1.8%vs 4.4±1.0%,P=0.005)in the HUMSC group.The HUMSC group showed a significantly higher collagen ?/? ratio than the saline group(3.5±0.6 vs 0.9±0.4,P<0.001).(2)In the HUMSC group,elastin accounted for 12.1%of the lamina propria,which was significantly higher than the corresponding value of 10.2%in the saline group(P=0.01).(3)Significantly more vWF-positive vessel profiles were observed in the HUMSC group than in the saline group(47±4 vs 70 ± 9,P=0.006).(4)Compared with the saline group,the thickness of the muscularis layer of the vagina was significantly increased in the HUMSC group(1205±90 ?m vs 1543±225 ?m,P=0.037).In addition,the fraction of smooth muscle in the nonvascular muscularis layer was 36.3%in the MSC group,which was significantly higher than the 26.0%in the saline group(P=0.001).(5)The elastic modulus in the HUMSC group was significantly higher than that in the saline group(4.1±1.0 vs 2.7±0.3 MPa,P=0.02).Conclusions:(1)HUMSC transplantation could repair the weak vaginal tissue of bilateral ovariectomized rhesus macaques.(2)HUMSC transplantation could promote extracellular matrix ingrowth,neovascularization and smooth muscle formation of the vagina in bilateral ovariectomized rhesus macaques.(3)HUMSC transplantation could improve the biomechanical properties of the vagina in bilateral ovariectomized rhesus macaques.(4)The potential of HUMSCs in the repair of vaginal tissue offers a new prospective treatment for POP. |
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