Xeno-immunosuppressive properties of human decidual stromal cells in mouse models of alloreactivity in vitro and in vivo

Sadeghi, Behnam; Heshmati, Yaser; Khoein, Bita; Kaipe, Helen; Uzunel, Mehmet; Walfridsson, Julian; Ringdén, Olle

doi:10.1016/j.jcyt.2015.09.001

Cited by 16 publications

(26 citation statements)

References 44 publications

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“…Although the immunological mechanisms involved in our in vivo experiments were not studied, several lines of experimental evidence confirm that MSCs function across species barriers [57]. In this connection, it has been shown before that human DSCs can interact with the rat and mouse immune systems [58,59]. The expression of HLA-G and the secretion of IL-10 by preDSCs [3] may be additional mechanisms involved in the induction of tolerance and escape from the immune response in xenotransplants [60,61].…”

Section: Discussionmentioning

confidence: 68%

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: Discussionmentioning

confidence: 68%

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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“…After the application of both exclusion and inclusion criteria, a total of 119 studies ( 33 – 151 ) were selected for analysis. Other 13 articles ( 152 – 164 ) were manually included for analysis in this systematic review after the reading of the articles previously selected and through the examination of their references.…”

Section: Resultsmentioning

confidence: 99%

“…Other 13 articles ( 152 – 164 ) were manually included for analysis in this systematic review after the reading of the articles previously selected and through the examination of their references. Therefore, a total of 132 manuscripts ( 33 – 164 ) formed the basis of this systematic review.…”

Section: Resultsmentioning

confidence: 99%

“…Medical complications that can occur following a hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and hemophagocytic lymphohistiocytosis were treated with hMSCs in 40 ( 33 – 70 – 72 ) and two studies ( 52 , 73 ), respectively. Chronic inflammatory disorders of the intestine such as Crohn's disease, ulcerative colitis and type II refractory celiac disease were treated with hMSCs in 19 ( 99 – 115 , 155 , 156 ), two ( 116 , 117 ) and one ( 118 ) manuscript, respectively.…”

Section: Resultsmentioning

confidence: 99%

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The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

et al. 2018

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Background: One of the greatest challenges for medicine is to find a safe and effective treatment for immune-related diseases. However, due to the low efficacy of the treatment available and the occurrence of serious adverse effects, many groups are currently searching for alternatives to the traditional therapy. In this regard, the use of human mesenchymal stem cells (hMSCs) represents a great promise for the treatment of a variety of immune-related diseases due to their potent immunomodulatory properties. The main objective of this study is, therefore, to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of the administration of hMSCs for the treatment of immune-related diseases was evaluated.Methods: The article search was conducted in PubMed/MEDLINE, Scopus and Web of Science databases. Original research articles assessing the therapeutic potential of hMSCs administration for the in vivo treatment immune-related diseases, published from 1984 to December 2017, were selected and evaluated.Results: A total of 132 manuscripts formed the basis of this systematic review. Most of the studies analyzed reported positive results after hMSCs administration. Clinical effects commonly observed include an increase in the survival rates and a reduction in the severity and incidence of the immune-related diseases studied. In addition, hMSCs administration resulted in an inhibition in the proliferation and activation of CD19+ B cells, CD4+ Th1 and Th17 cells, CD8+ T cells, NK cells, macrophages, monocytes, and neutrophils. The clonal expansion of both Bregs and Tregs cells, however, was stimulated. Administration of hMSCs also resulted in a reduction in the levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, IL-2, IL-12, and IL-17 and in an increase in the levels of immunoregulatory cytokines such as IL-4, IL-10, and IL-13.Conclusions: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.

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“…A study showed that mice treated with 9-Gy total body irradiation, HSCT, and very high doses of human DSCs (40 × 10 -6 /kg) died from pulmonary embolism [46]. …”

Section: Discussionmentioning

confidence: 99%

Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

Aronsson-Kurttila

Baygan²,

Moretti³

et al. 2018

Acta Haematol

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Background/Aims: Hemorrhagic cystitis (HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). Stromal cells have been tested as therapy for HC. Decidua stromal cells (DSCs) protect the fetus from the mother's immune system. Methods: Eleven patients with HC of grades 3-4 were treated with DSCs after HSCT. The median age was 33 years (range 8-50), and the median dose of DSCs was 1.5 × 10⁶/kg (range 0.7-2.5). The patients were given 1 dose (1-4). Results: In 5 patients, HC disappeared within 5 days after DSC infusion. Patients who received DSCs within 3 days after the start of HC had a duration of HC of 5 days and a shorter duration of pain than patients who were given DSCs later (p = 0.02). Three patients received DSCs prepared in albumin instead of AB-plasma and tended to have a shorter duration of pain (p = 0.07). There was no infusion toxicity. Adverse events were those often seen after HSCT. Nine of the 11 patients (82%) were alive 1 year after HSCT. Conclusions: Based on this pilot study, we started a randomized, placebo-controlled double-blind study using 2 doses of 1 × 10⁶ DSCs/kg suspended in albumin for treatment of early HC.

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Xeno-immunosuppressive properties of human decidual stromal cells in mouse models of alloreactivity in vitro and in vivo

Cited by 16 publications

References 44 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

The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

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