scholarly journals Mesenchymal Stromal Cells from Fetal and Maternal Placenta Possess Key Similarities and Differences: Potential Implications for Their Applications in Regenerative Medicine

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 127 ◽  
Author(s):  
Andrea Papait ◽  
Elsa Vertua ◽  
Marta Magatti ◽  
Sabrina Ceccariglia ◽  
Silvia De Munari ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Allogeneic Transplantation ◽  
Cell Polarization ◽  
T Regulatory Cell ◽  
T Lymphocyte Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Antigen Presenting

Placenta-derived mesenchymal stromal cells (MSC) have attracted more attention for their immune modulatory properties and poor immunogenicity, which makes them suitable for allogeneic transplantation. Although MSC isolated from different areas of the placenta share several features, they also present significant biological differences, which might point to distinct clinical applications. Hence, we compared cells from full term placenta distinguishing them on the basis of their origin, either maternal or fetal. We used cells developed by Pluristem LTD: PLacenta expanded mesenchymal-like adherent stromal cells (PLX), maternal-derived cells (PLX-PAD), fetal-derived cells (PLX-R18), and amniotic membrane-derived MSC (hAMSC). We compared immune modulatory properties evaluating effects on T-lymphocyte proliferation, expression of cytotoxicity markers, T-helper and T-regulatory cell polarization, and monocyte differentiation toward antigen presenting cells (APC). Furthermore, we investigated cell immunogenicity. We show that MSCs and MSC-like cells from both fetal and maternal sources present immune modulatory properties versus lymphoid (T cells) and myeloid (APC) cells, whereby fetal-derived cells (PLX-R18 and hAMSC) have a stronger capacity to modulate immune cell proliferation and differentiation. Our results emphasize the importance of understanding the cell origin and characteristics in order to obtain a desired result, such as modulation of the inflammatory response that is critical in fostering regenerative processes.

scholarly journals Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1401 ◽  
Author(s):  
Marta Magatti ◽  
Francesca Romana Stefani ◽  
Andrea Papait ◽  
Anna Cargnoni ◽  
Alice Masserdotti ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Immune Cell Subsets ◽  
New Perspective ◽  
Antigen Presenting ◽  
Open Question ◽  
Maternal Tolerance

During pregnancy, a successful coexistence between the mother and the semi-allogenic fetus occurs which requires a dynamic immune system to guarantee an efficient immune protection against possible infections and tolerance toward fetal antigens. The mechanism of fetal-maternal tolerance is still an open question. There is growing in vitro and in vivo evidence that mesenchymal stromal cells (MSC) which are present in perinatal tissues have a prominent role in generating a functional microenvironment critical to a successful pregnancy. This review highlights the immunomodulatory properties of perinatal MSC and their impact on the major immune cell subsets present in the uterus during pregnancy, such as natural killer cells, antigen-presenting cells (macrophages and dendritic cells), and T cells. Here, we discuss the current understanding and the possible contribution of perinatal MSC in the establishment of fetal-maternal tolerance, providing a new perspective on the physiology of gestation.

scholarly journals Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

2010 ◽  
Vol 11 (1) ◽  
pp. 11 ◽  
Author(s):  
Christina Holzwarth ◽  
Martin Vaegler ◽  
Friederike Gieseke ◽  
Stefan M Pfister ◽  
Rupert Handgretinger ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Proliferation And Differentiation ◽  
Oxygen Tensions

Mesenchymal Stromal Cells with Immunosuppressive Potential Can Be Mobilized Into Peripheral Blood by Electro-Acupuncture

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4805-4805
Author(s):  
Lizhen Liu ◽  
Qin Yu ◽  
Shan Fu ◽  
Hui Dong ◽  
Kaimin Hu ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Haematopoietic Stem Cell ◽  
Adherent Cells ◽  
Sprague Dawley ◽  
T Lymphocyte Proliferation ◽  
Immunosuppressive Property ◽  
Tgf Β1

Abstract Abstract 4805 Background: Mesenchymal stromal cells (MSCs) constitute a population of multipotential cells giving rise to adipocytes, osteoblasts and chondrocytes. Combining with their engraftment promoting capacity and immunosuppressive property, MSCs may be therapeutically useful for haematopoietic stem cell transplantation. A small number of MSCs can be mobilized into circulation by appropriate stimuli, such as hypoxia. However, there is little evidence for clinically useful methods for MSC mobilization. In this study, we used animal model to determine whether MSCs can be mobilized into peripheral blood (PB) by electro-acupuncture (EA), a traditional Chinese medical method. Design and Methods: Adult male Sprague-Dawley rats (200–220g) were randomly divided into there groups: EA-7 days, EA-14 days and control groups. For EA treatment, the rats were immobilized. A pair of stainless needles of 0.35mm diameter was inserted into points ‘Jizhong’ (GV6) and ‘Mingmen’ (DU4) and was then connected with output terminals of an EA apparatus. Alternating strings of dense-sparse frequencies were selected and the intensity was adjusted to induce slight twitch of the skin, with the intensity lasting for 30 min. Electro-acupuncture was applied to rats once a day for 7days or 14days. The control rats were immobilized for the same period without EA. To quantify the number of MSCs and evaluate mobilization efficiency, PB and bone barrow (BM) samples of each group were collected and colony-forming unit fibroblast (CFU-F) assays were performed. Mobilized PB derived MSCs were identified by immunophenotype and trilineage differentiation. Mixed lymphocyte reactions (MLR) were done to evaluate the immunosuppressive potential of mobilized MSCs and the cytokine levels TGF-β1, HGF and IL-10 in the supernatants of MSCs culture were measured by ELISA. Results: We found that MSCs can be mobilized into PB by electro-acupuncture. CFU-F frequency in rat PB was significantly increased after electro-acupuncture for 7days (8.20 ±1.48 vs.1.40 ±0.55 CFU-Fs per 3×106 cells) (p<0.05, n=5). PB CFU-F frequency increased to 12.4±1.82 per 3×106 cells in rats treated with electro-acupuncture for 14 days. However, no significant differences were observed in BM CFU-Fs among varies groups (P>0.05). Mobilized PB derived adherent cells were positive for CD90, CD29 and CD44, but negative for CD34 and CD45. After adipogenic, osteogenic, and chondrogenic induction, adherent cells from mobilized PB were positive for specific stains. In addition, they expressed mRNAs of Lpl and Pparg2 (adipocytic markers), Bglap and Runx2 (osteoblastic markers), and Col2a1 and Col10a1 (chondrocytic markers). These results showed that mobilized PB-derived cells could differentiate into adipocyte, osteoblast, and chondrocyte, which indicated that they are bona fide MSCs. The levels of immunosuppressive cytokines TGF-β1, HGF and IL-10 in the supernatants of PB-MSC culture were similar as BM MSCs. Results of MLR showed that mobilized PB derived MSCs inhibited T lymphocyte proliferation. Conclusion: Taken together, these data revealed, for the first time to the best of our knowledge, that multipotential MSCs can be mobilized by electro-acupuncture. Our study provides a clinical useful method to mobilize MSCs with immunosuppressive potential and highlight a novel insight into the mechanisms of electro-acupuncture therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Guoping Zheng ◽  
Menghua Ge ◽  
Guanguan Qiu ◽  
Qiang Shu ◽  
Jianguo Xu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spinal Cord Injuries ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cell Contact ◽  
Direct Cell ◽  
Almost All ◽  
Preclinical And Clinical Studies ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.

Regulation of TLR Expression and Activation in Human Mesenchymal Stromal Cells by IFN-a, IFN-g and TNF-a.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1790-1790
Author(s):  
Moïra François ◽  
Raphaëlle Romieu-Mourez ◽  
Marie-Noëlle Boivin ◽  
Jacques Galipeau
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Poly I:C ◽  
Marginal Effect ◽  
Human Mscs ◽  
Regulation Of Expression ◽  
Mesenchymal Progenitors ◽  
Polycytidylic Acid ◽  
Antigen Presenting ◽  
Molecular Patterns

Abstract Members of the toll-like receptor (TLR) family bind to pathogen-associated molecular patterns and subsequently induce the activation of the innate and adaptive immune responses. We investigated here the expression and role of TLRs in mesenchymal stromal cells (MSC), which are bone marrow-derived mesenchymal progenitors with recently described antigen presenting cell (APC) properties [Stagg et al, Blood (March 2006), Romieu et al., JI (in press)]. We observed that human MSCs express basal levels of TLR3 and TLR4, and these responded to their respective ligands, e.g. polycytidylic acid (poly I:C) or lipopolysaccharide (LPS), by the production of IL-6, IL-8 and IL-1b but not of active IL-12 p70 dimer. Exposure of MSCs to TNF-a increased the expression of TLR2 and TLR4 while IFN-a strongly upregulated TLR3 expression. By contrast, IFN-g had only a marginal effect on the expression of any TLR. IFN-a and poly I:C, as well as IFN-g and poly I:C or LPS were observed to work in synergy for the up-regulation of expression of several cytokines or inflammatory mediators, such as IL-12 p35 (IL-12A), TNF-a, RANTES, TRAIL, IFN-b and NOS2A in MSC. In contrast, none of these treatments induced the upregulation of IL-12 p40 (IL-12B), which may explain the lower levels of IL-12 p70 produced in MSCs compared to primary macrophages. Since c-Rel/p50 NF-kB dimers as well as IFN-induced IRF-1 were shown to control IL-12B and/or IL12A promoters, respectively, we next investigated expression of these transcription factors in MSCs. Results showed that MSC expressed the ubiquitous RelA NF-kB subunit but displayed significantly lower expression of c-Rel compared to macrophages. IRF-1 was upregulated following treatments with IFN-g or, to a lesser extent, with IFN-a. Therefore, the lower levels of IL-12 p70 seen in MSCs compared to macrophages may be explained by the absence of c-Rel in MSCs, which hinders the upregulation of IL-12A and IL-12B after exposure to single TLR ligands. However, the induction of IRF-1 by IFN-g or IFN-a may explain the synergistic effect observed in the upregulation of IL-12A in MSC treated with IFN-g or IFN-a and TLR ligands. In conclusion, TLR expression in human MSCs plays a role in their immune activation, although the outcome of this activation is different from the result of macrophage activation by TLR.

scholarly journals Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization

2017 ◽  
Vol 44 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
Dang-Dang Li ◽  
Liang Yue ◽  
Zhan-Qing Yang ◽  
Lian-Wen Zheng ◽  
Bin Guo
Keyword(s):  
Stromal Cells ◽  
Physiological Function ◽  
Embryo Implantation ◽  
Differentiation Markers ◽  
Mouse Uterus ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Implantation Sites ◽  
Implantation Period

Background/Aims: Hmgn2 is involved in regulating embryonic development, but its physiological function during embryo implantation and decidualization remains unknown. Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to examine the expression of Hmgn2 in mouse uterus during the pre-implantation period and explore its function and regulatory mechanisms in epithelial adhesion junction and stromal cell proliferation and differentiation. Results: Hmgn2 was primarily accumulated in uterine luminal epithelia on day 4 of pregnancy and subluminal stromal cells around the implanting blastocyst at implantation sites on day 5. Similar results were observed during delayed implantation and activation. Meanwhile, Hmgn2 expression was visualized in the decidua. In uterine epithelial cells, silencing of Hmgn2 by specific siRNA reduced the expression of adhesion molecules Cdh1, Cdh2 and Ctnnb1 and enhanced the expression of Muc1, whereas constitutive activation of Hmgn2 exhibited the opposite effects, suggesting a role for Hmgn2 in attachment reaction during embryo implantation. Estrogen stimulated the expression of Hmgn2 in uterine epithelia, but the stimulation was abrogated by ER antagonist ICI 182,780. Further analysis evidenced that attenuation of Hmgn2 might eliminate the regulation of estrogen on the expression of Cdh1, Cdh2 and Ctnnb1. In uterine stromal cells, progesterone induced the accumulation of Hmgn2 which advanced the expression of Prl8a2 and Prl3c1, two well-known differentiation markers for decidualization, but did not affect the proliferation of stromal cells. Knockdown of Hmgn2 blocked the progesterone-induced differentiation of uterine stromal cells. Moreover, Hmgn2 might serve as an intermediate to mediate the regulation of progesterone on Hand2. Conclusion: Hmgn2 may play an important role during embryo implantation and decidualization.

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