Bone marrow mesenchymal stem cells could acquire the phenotypes of epithelial cells and accelerate vaginal reconstruction combined with small intestinal submucosa

Abstract

Grafting material for vaginal reconstruction commonly includes the bowel, peritoneum, skin, and amniotic membrane. Bone marrow mesenchymal stem cells (MSCs) have the potential of multilineage differentiation into a variety of cells and have been widely explored in tissue engineering. In the current study, we examined whether MSCs could be differentiated to vaginal epithelial cells (VECs) upon co-culturing with VECs. We also examined whether Wnt/β-catenin signaling pathway is implicated in such differentiation. Co-culture of MSCs with VECs using a transwell insert system (with no direct contact) induced the expression of VECs marker AE1/AE3 in MSCs. MSCs combined with small intestinal submucosa (SIS) scaffold were implanted in place of the native vagina in rats to observe the implications for vaginal reconstruction in vivo. Anatomic repair of neovagina was assessed by histological staining for H/E and Masson's Trichrome. GSK-3β and β-catenin, main members of Wnt/β-catenin signaling pathway, in MSCs were increased upon co-culturing with VECs. Exposure of co-cultured MSCs to a Wnt/β-catenin signaling activator, lithium chloride (LiCl, 20 µM) increased phosphorylated GSK-3β and β-catenin and enhanced expression of AE1/AE3. In vivo-grafted cells displayed significant matrix infiltration and expressed epithelial markers in neovagina. These findings suggest that MSCs could acquire the phenotype of VECs when co-cultured with VECs, possibly via activation of Wnt/β-catenin signaling. MSCs provide an alternative cell source for potential use in vaginal tissue engineering.

Bone Marrow Mesenchymal Stem Cells Accelerate the Morphological and Functional Recovery of Neovaginas

“…MSCs are widely used in tissue engineering. In the present study, we found that an epithelium had covered the whole neovagina at the 4th week, which is consistent with our previous study , and we found that the epithelium became more mature at the 12th week. More smooth muscle and nerve tissue were found in the neovaginas of the SIS+MSCs group than in those of the SIS group.…”

“…All relevant protocols were approved by the Institutional Animal Care and Use Committee of Hebei Medical University. The isolation and culture of bone marrow‐derived MSCs was performed as described previously . Briefly, Sprague‐Dawley rats, 2–5 weeks old, were sacrificed by cervical dislocation.…”

“…MSCs from the third passage were collected for use. Characterization of the MSCs, including the expression profiles of surface molecules and multilineage differentiation, was performed in our early studies .…”

“…Ideal vaginal reconstruction involves not only morphological recovery but also functional recovery, which needs the regeneration of smooth muscle and nerve tissue. Our previous investigations showed that MSCs may accelerate the regeneration of epithelium. In this study, we prolonged the observation time and tried to assess the morphological and functional recovery of the neovagina in a rat model.…”

Bioengineering Strategies to Treat Female Infertility

“…Vaginal agenesis, the congenital underdevelopment of the vagina, occurs in 1 out of 5000 females. [55][56][57] Various biomaterials have been used to fabricate vaginal grafts, including dermal matrix, 55,56,[58][59][60][61] SIS, 53,[62][63][64][65][66][67] and human amniotic membrane. 68 Recently, there have been several investigators that explored different biomaterials and cell sources to create tissue engineered constructs for vaginal agenesis therapies (Table 3).…”