The utility of human fallopian tube mucosa as a novel source of multipotent stem cells for the treatment of autologous reproductive tract injury

Abstract

IntroductionFallopian tube, which is normally discarded in surgical procedures, has proven to be a source of mesenchymal stem cells (MSCs) with increasing evidence. However, fallopian tube mucosa, which can be acquired via non-invasive procedures, is a previously unknown source of MSCs. In the present study, we explored the existence of MSCs in the human fallopian tube mucosa and also compared multipotent stem cells derived from fallopian tubes and fallopian tube mucosa according to their biological characteristics and therapeutic potential for treatment of autologous reproductive tract injury.MethodsCells isolated from human fallopian tubes and fallopian tube mucosa were expanded and characterised by flow cytometry. The proliferative capacity of both cell types was measured by performing colony-forming unit-fibroblast and Cell Counting Kit-8 assays. Both cell types underwent in vitro adipogenic, chondrogenic, and osteogenic differentiation. The expression of osteocyte-, adipocyte-, and chondrocyte-related genes in the differentiated cell lineages was assessed by reverse transcription-polymerase chain reaction. The secretion of growth factors and immunomodulatory cytokines by both cell types were measured by enzyme-linked immunosorbent assays.ResultsWe found that MSCs existed in the fallopian tube mucosa. The comparison between human fallopian tube MSCs (hFTMSCs) and human fallopian tube mucosa MSCs (hFMMSCs) showed that hFTMSCs had a stronger proliferative capacity and shorter duplication time than hFMMSCs. Both cell types could be differentiated into adipocytes, osteoblasts, or chondrocytes in vitro. Real-time polymerase chain reaction analysis demonstrated that hFTMSCs displayed increased expression of osteogenic-specific genes compared with hFMMSCs, but the two types of cells showed no significant increase in the mRNA expression of adipogenic-specific or chondrogenic-specific genes. hFMMSCs and hFTMSCs robustly produced a variety of growth factors and immunomodulatory cytokines.ConclusionsHuman fallopian tube mucosa is a novel source of multipotent cells. hFMMSCs demonstrated stronger proliferative capacity and superior secretion of growth factors and immunomodulatory cytokines than hFTMSCs, making the former a better source of stem cells for the treatment of autologous reproductive tract injury. Compared with fallopian tube, fallopian tube mucosa has more wide-ranging applications and can be used to carry out autologous transplantation.

Autologous, Non-Invasively Available Mesenchymal Stem Cells from the Outer Root Sheath of Hair Follicle Are Obtainable by Migration from Plucked Hair Follicles and Expandable in Scalable Amounts

“…This further enables a clean-cut extraction of the follicle with minimal to no loss of the ORS tissue. The small amount of tissue that is being withdrawn from the skin can only be compared to that of inner tissue invasive biopsies such as retina or fallopian tube [18].…”

“…Although MSCs are recognized as a somatic stem cell base for clinical applications [9], they are no exception to the aforementioned limitations. While they can be routinely sampled from human bone marrow [10], peripheral blood [11], adipose tissue [12,13], lung [14], wisdom teeth [15], deciduous teeth [16], synovial fluid [17], fallopian tubes [18] placenta [19], and umbilical cord blood [20], the only known source of non-invasively and stably available autologous MSCs, as well as stem cells in general, is the outer root sheath (ORS) of hair follicle [21].…”

Neisseria gonorrhoeae Challenge Increases Matrix Metalloproteinase-8 Expression in Fallopian Tube Explants

“…MMP-8 is a neutrophil collagenase, but it can also be expressed by fibroblast and endothelial cells (Danielsen et al, 2011 ). In the case of ampullar FTs explants this was also corroborated by immunohistochemistry, were MMP-8 was found to be also located in the stroma (Figure 2 ) that is mainly composed by fibroblast-mesenchymal cells (Wang et al, 2015 ). In FTs connective tissue, fibers of Collagen I and II are expressed (Schultka et al, 1989 ).…”

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube

“…iPSCs first need to be induced to differentiate into intermediate mesoderm-like cells, and can subsequently be treated with Wnt pathway agonists (Wnt4 and Follistatin) to generate a fallopian tube epithelium that contains both ciliated and secretory cells. It is also possible to isolate multipotent mesenchymal stem cells (MSCs) from whole human fallopian tube tissue, as well as a subset of less proliferative MSCs from the mucosal portion of the tissue alone ( 174 ). These cells are capable of differentiation on adipogenic, osteogenic, and chondrogenic pathways and produce cytokines such as GM-CSF, IL-4, IL-6, TNFα and IFNγ.…”