Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion

Abstract

Background: Human decidual stromal cells (DSCs) are involved in the maintenance and development of pregnancy, in which they play a key role in the induction of immunological maternal-fetal tolerance. Precursors of DSCs (preDSCs) are located around the vessels, and based on their antigen phenotype, previous studies suggested a relationship between preDSCs and mesenchymal stromal/stem cells (MSCs). This work aimed to further elucidate the MSC characteristics of preDSCs. Methods:We established 15 human preDSC lines and 3 preDSC clones. Physiological differentiation (decidualization) of these cell lines and clones was carried out by in vitro culture with progesterone (P4) and cAMP. Decidualization was confirmed by the change in cellular morphology and prolactin (PRL) secretion, which was determined by enzyme immunoassay of the culture supernatants. We also studied MSC characteristics: (1) In mesenchymal differentiation, under appropriate culture conditions, these preDSC lines and clones differentiated into adipocytes, osteoblasts, and chondrocytes, and differentiation was confirmed by cytochemical assays and RT-PCR. (2) The expression of stem cell markers was determined by RT-PCR. (3) Cloning efficiency was evaluated by limited dilution. (4) Immunoregulatory activity in vivo was estimated in DBA/2-mated CBA/J female mice, a murine model of immune-based recurrent abortion. (5) Survival of preDSC in immunocompetent mice was analyzed by RT-PCR and flow cytometry.Results: Under the effect of P4 and cAMP, the preDSC lines and clones decidualized in vitro: the cells became rounder and secreted PRL, a marker of physiological decidualization. PreDSC lines and clones also exhibited MSC characteristics. They differentiated into adipocytes, osteoblasts, and chondrocytes, and preDSC lines expressed stem cell markers OCT-4, NANOG, and ABCG2; exhibited a cloning efficiency of 4 to 15%; significantly reduced the embryo resorption rate (P < 0.001) in the mouse model of abortion; and survived for prolonged periods in immunocompetent mice. The fact that 3 preDSC clones underwent both decidualization and mesenchymal differentiation shows that the same type of cell exhibited both DSC and MSC characteristics.(Continued on next page)

An efficient protocol to generate placental chorionic plate-derived mesenchymal stem cells with superior proliferative and immunomodulatory properties

“…It is reported that bone mesenchymal stem cells improve pregnancy outcome by inducing maternal tolerance to the allogeneic fetus in abortion-prone matings in mouse [45]. Another study shows that MSCs have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion, which may be relevant in the decidual mechanisms of maternal–fetal immune tolerance [46]. Both studies indicate MSCs possess the ability to improve maternal–fetal immune tolerance.…”

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

“…In the past few years, the endometrial therapeutic effects of MSCs derived from different tissues such as bone marrow [ 17 ], umbilical cord [ 18 , 19 ], human decidual [ 20 ], and uterus [ 21 ] have been investigated intensively, thus, providing new approaches to restore the endometrium to its normal morphology and function. In particular, the umbilical cord Wharton’s jelly was reported to be an ideal source of stem cells for clinical treatment and scientific research applications because of its highest concentration of allogeneic MSCs compared to that of other tissues [ 22 ].…”

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

“…In the past few years, the endometrial therapeutic effects of MSCs derived from different tissues such as bone marrow [17] , umbilical cord [18,19] , human decidual [20] , and uterus [21] have been investigated intensively, thus, providing new approaches to restore the endometrium to its normal morphology and function. In particular, the umbilical cord Wharton's jelly was reported to be an ideal source of stem cells for clinical treatment and scienti c research applications because of its highest concentration of allogeneic MSCs compared to that of other tissues [22] .…”