Mesenchymal stem cell transplantation for vaginal repair in an ovariectomized rhesus macaque model

Abstract

Abstract Background Current surgical therapies for pelvic organ prolapse (POP) do not repair weak vaginal tissue and just provide support; these therapies may trigger severe complications. Stem cell-based regenerative therapy, due to its ability to reconstruct damaged tissue, may be a promising therapeutic strategy for POP. The objective of this study is to evaluate whether mesenchymal stem cell (MSC) therapy can repair weak 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 MSC group. Three months after ovariectomy, saline or MSCs were injected in situ into the injured vaginal wall. The vaginal tissue was harvested 12 weeks after 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. Data analysis was performed with unpaired Student’s t test or Mann-Whitney. Results Twelve weeks after MSC transplantation, histological and biochemical analyses revealed that the content of collagen I, elastin, and microvascular density in the lamina propria of the vagina increased significantly in the MSC group compared with the saline group. And the fraction of smooth muscle in the muscularis of vagina increased significantly in the MSC group. In addition, MSC transplantation improved the biomechanical properties of the vagina by enhancing the elastic modulus. Conclusion Vaginal MSC transplantation could repair the weak vaginal tissue by promoting extracellular matrix ingrowth, neovascularization, and smooth muscle formation and improve the biomechanical properties of the vagina, providing a new prospective treatment for POP.

Keywords

• Human umbilical cord mesenchymal stem cell
• Pelvic organ prolapse
• Rhesus macaque model
• Vaginal repair