Abstract
BackgroundCurrent 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.MethodsA 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.ResultsTwelve 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.ConclusionVaginal 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.
Highlights
Current surgical therapies for pelvic organ prolapse (POP) do not repair weak vaginal tissue and just provide support; these therapies may trigger severe complications
Isolation and characterization of mesenchymal stem cell (MSC) A schematic of the MSC isolation and characterization protocol is shown in Supplementary Figure 1
Flow cytometric analysis showed positive expression of CD90, CD105, CD73, CD29, and CD44 and low expression of CD34 and CD45, indicating that the cells isolated from human umbilical cord had MSC characteristics
Summary
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. Surgical strategies for POP repair mainly include native tissue repair and mesh-augmented repair strategies. Native tissue repair has high objective failure rates, and mesh repair has a reduced failure rate, postoperative complications such as infection, chronic pain, and vaginal erosion have caused international controversies, limiting its use [7, 8]. The development of a novel therapeutic strategy for POP with a high cure rate and few complications is needed
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