Human predecidual stromal cells have distinctive characteristics of pericytes: Cell contractility, chemotactic activity, and expression of pericyte markers and angiogenic factors

Muñoz-Fernández, Raquel; Mata, Claudia De La; Prados, Alejandro; Perea, Ana; Ruiz-Magaña, María José; Llorca, Tatiana; Fernández-Rubio, Pablo; Blanco, Osmany; Abadía-Molina, Ana Clara; Olivares, Enrique G.

doi:10.1016/j.placenta.2017.11.010

Cited by 21 publications

(33 citation statements)

References 48 publications

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“…These lines consisted of a highly purified, uniform, adherent cell population in which almost all cells expressed the endometrial stromal cell marker CD10 [35], together with CD13, CD29, CD44, CD73, CD90, CD105, α-smooth muscle (SM) actin, nestin, podoplanin, and vimentin, and lacked CD15, CD19, CD34, CD45, CD62P, and HLA-DR expression. This antigen phenotype is fully compatible with that of bone marrow MSCs [19,36] (Table 1). To establish HFF lines from the human foreskin, we used the method described by Kimatrai and colleagues [28] to establish preDSC lines from the decidua.…”

Section: Isolation and Culture Of Predsc And Hff Linessupporting

confidence: 64%

“…Furthermore, experimental evidence showed strong similarities between pericytes and mesenchymal stromal/stem cells (MSCs), and some have proposed that they constitute the same cell population [22][23][24]. In this connection, we previously confirmed that the antigen phenotype of preDSCs is compatible with MSCs [5,19,25]. Functions such as cell contractility, resistance to apoptosis, and inhibition of lymphocyte apoptosis are also shared by MSCs and preDSCs [18,[26][27][28][29][30].…”

Section: (Continued From Previous Page)supporting

confidence: 60%

“…The isolation and maintenance of highly purified human preDSC lines in culture allowed us to analyze the antigen phenotype of these cells and study their functions [3-5, 18, 19]. Based on the perivascular location of preDSCs, together with their expression of pericyte markers and angiogenic factors, their phagocytic activity, and their capacity to contract in vitro, we demonstrated a close relationship between preDSCs and pericytes [19], contractile cells that surround microvascular endothelial cells [20,21]. Furthermore, experimental evidence showed strong similarities between pericytes and mesenchymal stromal/stem cells (MSCs), and some have proposed that they constitute the same cell population [22][23][24].…”

Section: (Continued From Previous Page)mentioning

confidence: 99%

“…We used the preDSC lines obtained in recent work as reported earlier [19]. These lines consisted of a highly purified, uniform, adherent cell population in which almost all cells expressed the endometrial stromal cell marker CD10 [35], together with CD13, CD29, CD44, CD73, CD90, CD105, α-smooth muscle (SM) actin, nestin, podoplanin, and vimentin, and lacked CD15, CD19, CD34, CD45, CD62P, and HLA-DR expression.…”

Section: Isolation and Culture Of Predsc And Hff Linesmentioning

confidence: 99%

“…We used three preDSC clones obtained in earlier work [19]. Predecidual stromal cell clones were obtained from preDSC lines by limiting dilution in 96-well plates, using complete Opti-MEM supplemented with 10% FCS.…”

Section: Cell Cloningmentioning

confidence: 99%

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

et al. 2019

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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)

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Section: Isolation and Culture Of Predsc And Hff Linessupporting

confidence: 64%

Section: (Continued From Previous Page)supporting

confidence: 60%

Section: (Continued From Previous Page)mentioning

confidence: 99%

Section: Isolation and Culture Of Predsc And Hff Linesmentioning

confidence: 99%

Section: Cell Cloningmentioning

confidence: 99%

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

et al. 2019

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Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy

Signorelli

Ayoglu

Johansson

et al. 2019

J cachexia sarcopenia muscle

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Background Duchenne muscular dystrophy (DMD) is a fatal disease for which no cure is available. Clinical trials have shown to be largely underpowered due to inter-individual variability and noisy outcome measures. The availability of biomarkers able to anticipate clinical benefit is highly needed to improve clinical trial design and facilitate drug development.Methods In this study, we aimed to appraise the value of protein biomarkers to predict prognosis and monitor disease progression or treatment outcome in patients affected by DMD. We collected clinical data and 303 blood samples from 157 DMD patients in three clinical centres; 78 patients contributed multiple blood samples over time, with a median follow-up time of 2 years. We employed linear mixed models to identify biomarkers that are associated with disease progression, wheelchair dependency, and treatment with corticosteroids and performed survival analysis to find biomarkers whose levels are associated with time to loss of ambulation. Results Our analysis led to the identification of 21 proteins whose levels significantly decrease with age and nine proteins whose levels significantly increase. Seven of these proteins are also differentially expressed in non-ambulant patients, and three proteins are differentially expressed in patients treated with glucocorticosteroids. Treatment with corticosteroids was found to partly counteract the effect of disease progression on two biomarkers, namely, malate dehydrogenase 2 (MDH2, P = 0.0003) and ankyrin repeat domain 2 (P = 0.0005); however, patients treated with corticosteroids experienced a further reduction on collagen 1 serum levels (P = 0.0003), especially following administration of deflazacort. A time to event analysis allowed to further support the use of MDH2 as a prognostic biomarker as it was associated with an increased risk of wheelchair dependence (P = 0.0003). The obtained data support the prospective evaluation of the identified biomarkers in natural history and clinical trials as exploratory biomarkers. Conclusions We identified a number of serum biomarkers associated with disease progression, loss of ambulation, and treatment with corticosteroids. The identified biomarkers are promising candidate prognostic and surrogate biomarkers, which may support drug developers if confirmed in prospective studies. The serum levels of MDH2 are of particular interest, as they correlate with disease stage and response to treatment with corticosteroids, and are also associated with the risk of wheelchair dependency and pulmonary function.

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Pericytes in the Placenta: Role in Placental Development and Homeostasis

Barreto

Romagnolli

Cereta

et al. 2019

Advances in Experimental Medicine and Biology

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Human predecidual stromal cells have distinctive characteristics of pericytes: Cell contractility, chemotactic activity, and expression of pericyte markers and angiogenic factors

Cited by 21 publications

References 48 publications

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

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

Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy

Pericytes in the Placenta: Role in Placental Development and Homeostasis

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