Human Amniotic Membrane-Derived Mesenchymal and Epithelial Cells Exert Different Effects on Monocyte-Derived Dendritic Cell Differentiation and Function

Abstract

We previously demonstrated that mesenchymal cells from human amniotic membrane (hAMTCs) inhibit the generation and maturation of monocyte-derived dendritic cells (DCs) in vitro. Considering the crucial role of DCs in the immune response and that epithelial cells of the human amniotic membrane (hAECs) share some of the immunoregulatory properties of hAMTCs, we investigated whether hAECs also modulate monocytederived DCs. We compared hAECs with hAMTCs in a cell-to-cell contact setting and their secreted factors in modulating DC differentiation and function. First, we demonstrated that primary and expanded hAMTCs strongly inhibited the differentiation of DCs and induced a shift toward M2-like macrophages. This was observed when hAMTCs were cultured in contact (hAMTC-DC cont ) or in Transwells (hAMTC-DC tw ) with monocytes and even when medium conditioned by hAMTCs was used instead of hAMTCs. hAECs also prevented DC development, but to a lesser extent than hAMTCs. hAECs were more effective when cultured in contact with monocytes (hAEC-DC cont ) rather than in Transwells (hAEC-DC tw ). The modulatory capacity of hAECs changed during passaging unlike the hAMSCs. The ability to stimulate CD4 + and CD8 + T-cell proliferation was almost completely abolished by hAMTC-DC cont , whereas hAMTC-DC tw and hAEC-DC cont displayed only a reduced ability to stimulate CD8 + T cells. Furthermore, monocytes cocultured with hAMTCs and hAECs showed some similarities, but also differences in cytokine/chemokine secretion. Similarities were observed in the inhibition of IL-12p70 and TNF-a and the increase in IL-10 in supernatants taken from monocyteDCs cocultured with hAMTCs and hAECs in contact and Transwell settings. The inflammatory factors IL-8, CXCL9, and MIP-1a were significantly lower in hAMTC-DC cont , hAMTC-DC tw , and hAEC-DC cont conditions. In contrast, only hAMTCs (in both contact and Transwell conditions) were able to significantly increase IL-1b and CCL2. Altogether, we demonstrated that hAMTCs and hAECs affect DC differentiation, but that hAMTCs exerted a stronger inhibitory effect, abolished T-cell proliferation, and also induced more changes in cytokine/ chemokine production.

Extract of fetal membrane would inhibit thrombosis and hemolysis

“…Moreover, Pro-inflammatory cytokines including IL-1a and IL-1b are also down regulated by the AM [13]. In addition, both amniotic epithelial and mesenchymal cells have the ability to down-regulate the expression of TNF-a in monocyte-derived dendritic cells [58]. Therefore, the AM could inhibit coagulation by inhibiting inflammation.…”

Internalization of nanopolymeric tracers does not alter characteristics of placental cells

“…One of the hallmark properties of placental MSC is their immune modulatory ability [9,11,12,33,34]. In fact, the use of placental MSC has proven beneficial in preclinical models of diseases with underlying altered inflammatory processes [11,17], altogether rendering these cells attractive therapeutic options.…”

“…Furthermore, the monocyte-macrophage compartment is also influenced by hAMSC. Specifically, we have recently demonstrated that hAMSC block monocyte differentiation towards dendritic cells and induce their macrophage differentiation [12]. MSC isolated from placental villi exert similar immune modulatory effects both versus T cells [13] and monocytes [14].…”

Effect of human amniotic epithelial cells on pro‐fibrogenic resident hepatic cells in a rat model of liver fibrosis

“…hAEC were isolated from term placentas ( n = 5) as previously described . Briefly, the amnion was detached from chorion and washed in PBS (Sigma‐Aldrich, St Louis, MO, USA) supplemented with 100 U/ml penicillin (Lonza, Basel, Switzerland) and 100 μg/ml streptomycin (Sigma‐Aldrich).…”

“…Animal experiments were carried out in accordance with the guidelines established by the Italian law DL 26/2014 on the accommodation and care of animals used for scientific purposes. The hAEC isolation hAEC were isolated from term placentas (n = 5) as previously described [24]. Briefly, the amnion was detached from chorion and washed in PBS (Sigma-Aldrich, St Louis, MO, USA) supplemented with 100 U/ml penicillin (Lonza, Basel, Switzerland) and 100 lg/ml streptomycin (Sigma-Aldrich).…”