scholarly journals The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity

2019 ◽  
Vol 8 (7) ◽  
pp. 1025 ◽  
Author(s):  
Yueyuan Zhou ◽  
Yusuke Yamamoto ◽  
Zhongdang Xiao ◽  
Takahiro Ochiya
Keyword(s):  
Stem Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Cell Types ◽  
Paracrine Signaling ◽  
Immune Microenvironment ◽  
Paracrine Factors ◽  
Diverse Range ◽  
Almost All ◽  
Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) exist in almost all tissues, possessing the potential to differentiate into specialized cell types and exert immunomodulatory functions. Thus, they have attracted much attention as a promising therapeutic candidate. Recent studies have demonstrated that paracrine signaling is mainly responsible for the involvement of MSCs in the modulation of immune responses and the progression of diseases. Through release of secretome consisting of a diverse range of cytokines, chemokines, and extracellular vesicles (EVs), MSCs convey regulatory messages to recipient immune cells in the microenvironment. In this review, we focus on the recent advances in how MSCs contribute to immunomodulation through the secretion of paracrine factors. The further improved understanding of the molecular mechanism underlying the interactions between MSCs and immune cells highlights the paracrine biology of MSCs in the modulation of the immune microenvironment and promotes the clinical application of MSCs in regenerative medicine and immune diseases.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Adipose-derived stromal/stem cells improve epidermal homeostasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariko Moriyama ◽  
Shunya Sahara ◽  
Kaori Zaiki ◽  
Ayumi Ueno ◽  
Koichi Nakaoji ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Culture System ◽  
Wound Repair ◽  
Cell Types ◽  
Skin Wound ◽  
Epidermal Keratinocytes ◽  
Stromal Stem Cells ◽  
Collagen Vitrigel

AbstractWound healing is regulated by complex interactions between the keratinocytes and other cell types including fibroblasts. Recently, adipose-derived mesenchymal stromal/stem cells (ASCs) have been reported to influence wound healing positively via paracrine involvement. However, their roles in keratinocytes are still obscure. Therefore, investigation of the precise effects of ASCs on keratinocytes in an in vitro culture system is required. Our recent data indicate that the epidermal equivalents became thicker on a collagen vitrigel membrane co-cultured with human ASCs (hASCs). Co-culturing the human primary epidermal keratinocytes (HPEK) with hASCs on a collagen vitrigel membrane enhanced their abilities for cell proliferation and adhesion to the membrane but suppressed their differentiation suggesting that hASCs could maintain the undifferentiated status of HPEK. Contrarily, the effects of co-culture using polyethylene terephthalate or polycarbonate membranes for HPEK were completely opposite. These differences may depend on the protein permeability and/or structure of the membrane. Taken together, our data demonstrate that hASCs could be used as a substitute for fibroblasts in skin wound repair, aesthetic medicine, or tissue engineering. It is also important to note that a co-culture system using the collagen vitrigel membrane allows better understanding of the interactions between the keratinocytes and ASCs.

scholarly journals Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiel van Geffen ◽  
Astrid Deißler ◽  
Markus Quante ◽  
Harald Renz ◽  
Dominik Hartl ◽  
...  
Keyword(s):  
Immune System ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Responses ◽  
Immune Cells ◽  
Current Knowledge ◽  
Suppressor Cells ◽  
Interstitial Lung Diseases ◽  
Stromal Stem Cells

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.

scholarly journals PDTM-14. INTERACTIONS BETWEEN IMMUNE MICROENVIRONMENT, STEM CELLS, AND CELL PROLIFERATION IN PEDIATRIC EMBRYONAL CENTRAL NERVOUS SYSTEM [CNS] TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi189-vi190
Author(s):  
Kristian Schafernak ◽  
Emma Utagawa ◽  
Shwetal Mehta ◽  
Tiffany Di Modica ◽  
Elliott Mufson ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Immune Cells ◽  
Cns Tumors ◽  
Stem Cell Marker ◽  
Proliferation Index ◽  
Cytotoxic T Cell ◽  
Cell Marker ◽  
Tumor Associated Macrophages ◽  
Immune Microenvironment

Abstract Mounting evidence suggests the brain’s own immune cells, microglia, and perivascular macrophages play important roles in immune surveillance/inflammation, but also support proliferation/growth of gliomas, possibly through interactions with tumor stem cells. Immune cells are increasingly regarded as potential targets for cancer therapy, however, the immune microenvironment has not been well-studied in pediatric embryonal CNS tumors. In a series of 13 medulloblastomas, 7 PNETs and 6 ATRTs, we quantified the number of cells immunopositive for macrophage/microglia Ionizing calcium binding adaptor molecule 1 [Iba1], CD68 (expressed on both “M1” antitumor/proinflammatory macrophages and “M2” protumor/anti-inflammatory macrophages), CD163 (“M2” macrophages), CD3 (T-cell marker), CD4 (helper T cell), CD8 (cytotoxic T cell) and CD20 (B-cell marker) and correlated these findings with the stem-cell marker nestin and the Ki67/MIB1 proliferation index. Significant results were as follows: Across groups, CD68 showed a strong Spearman rank-order correlation with both CD163 (r=0.610, p=0.0007) and nestin (r=0.577, p=0.0017), while CD3 correlated strongly with CD8 (r=0.601, p=0.004), CD4 (r=0.526, p=0.005) and CD20 (r=0.499, p=0.008). Between groups, the number of CD163-positive cells was significantly higher in PNETs compared to medulloblastomas (p=0.035). Within the medulloblastoma group, CD68 showed a significant relationship with nestin (r=0.595, p=0.0387) and Ki67 (r=0.606, p=0.0333), and there was a robust correlation between CD4 and CD8 values (r=0.846, p=0.0000002). Within PNETs, there was a strong negative correlation between CD163 and nestin (r=-0.883, p=0.0000002), while CD68 correlated with CD4 (r=0.803, p=0.006). Within ATRTs, nestin and Ki67 were strongly correlated (r=1.000, p=0.0028) as were CD68 and CD163 (r=0.943, p=0.017). These data suggest a role for blocking embryonal CNS tumor-associated macrophages by inhibiting the CSF1R pathway (perhaps in conjunction with CD8-positive T cells which could antagonize the immunosuppressive function of tumor-associated macrophages) or reprogramming them from an M2 to an M1 phenotype (particularly in PNETs, which had the highest number of CD163-positive cells).

scholarly journals Immunohistochemical and Molecular Characterization of the Human Periosteum

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sönke Percy Frey ◽  
Hendrik Jansen ◽  
Stefanie Doht ◽  
Luis Filgueira ◽  
Rene Zellweger
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Immune Cells ◽  
Precursor Cells ◽  
Rt Pcr ◽  
Phenotypic Properties ◽  
Mhc Ii ◽  
Cambium Layer ◽  
Stromal Stem Cells

Purpose. The aim of the present study was to characterize the cell of the human periosteum using immunohistological and molecular methods.Methods. Phenotypic properties and the distribution of the cells within the different layers were investigated with immunohistochemical staining techniques and RT-PCR, focussing on markers for stromal stem cells, osteoblasts, osteoclasts and immune cells.Results. Immunohistochemical results revealed that all stained cells were located in the cambium layer and that most cells were positive for vimentin. The majority of cells consisted of stromal stem cells and osteoblastic precursor cells. The density increased towards the deeper layers of the cambium. In addition, cells positive for markers of the osteoblast, chondrocyte, and osteoclast lineages were found. Interestingly, there were MHC class II-expressing immune cells suggesting the presence of dendritic cells. Using lineage-specific primer pairs RT-PCR confirmed the immunofluorescence microscopy results, supporting that human periosteum serves as a reservoir of stromal stem cells, as well as cells of the osteoblastic, and the chondroblastic lineage, osteoclasts, and dendritic cells.Conclusion. Our work elucidates the role of periosteum as a source of cells with a high regenerative capacity. Undifferentiated stromal stem cells as well as osteoblastic precursor cells are dominating in the cambium layer. A new outlook is given towards an immune response coming from the periosteum as MHC II positive immune cells were detected.

scholarly journals Comparative Transcriptomics Identifies Potential Stemness-Related Markers for Mesenchymal Stromal/Stem Cells

2021 ◽  
Author(s):  
Myret Ghabriel ◽  
Ahmed El Hosseiny ◽  
Ahmed Moustafa ◽  
Asma Amleh
Keyword(s):  
Stem Cells ◽  
Cellular Therapy ◽  
Genetic Interaction ◽  
Antioxidant Defense System ◽  
Cell Types ◽  
Multipotent Cells ◽  
The Common ◽  
Regenerative Therapies ◽  
Stromal Stem Cells ◽  
Human And Mouse

Mesenchymal stromal/stem cells (MSCs) are multipotent cells residing in multiple tissues with the capacity for self-renewal and differentiation into various cell types. These properties make them promising candidates for regenerative therapies. MSC identification is critical in yielding pure populations for successful therapeutic applications; however, the criteria for MSC identification proposed by the International Society for Cellular Therapy (ISCT) is inconsistent across different tissue sources. In this study, we aimed to identify potential markers to be used together with the ISCT criteria to provide a more accurate means of MSC identification. Thus, we carried out a comparative analysis of the expression of human and mouse MSCs derived from multiple tissues to identify the common differentially expressed genes. We show that six members of the proteasome degradation system are similarly expressed across MSCs derived from bone marrow, adipose tissue, amnion, and umbilical cord. Also, with the help of predictive models, we found that these genes successfully identified MSCs across all the tissue sources tested. Moreover, using genetic interaction networks, we showed a possible link between these genes and antioxidant enzymes in the MSC antioxidant defense system, thereby pointing to their potential role in prolonging the life span of MSCs. Our results suggest that these genes can be used as stemness-related markers.

scholarly journals Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism

2021 ◽  
Vol 11 ◽  
Author(s):  
Jeu Park ◽  
Jee Hyung Sohn ◽  
Sang Mun Han ◽  
Yoon Jeong Park ◽  
Jin Young Huh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Immune Responses ◽  
Immune Cells ◽  
Adipose Stem Cells ◽  
Cellular Interactions ◽  
Multiple Impacts ◽  
Lipid Antigens ◽  
Lipid Metabolites ◽  
Underlying Mechanisms

Accumulating evidence reveals that adipose tissue is an immunologically active organ that exerts multiple impacts on the regulation of systemic energy metabolism. Adipose tissue immunity is modulated by the interactions between adipocytes and various immune cells. Nevertheless, the underlying mechanisms that control inter-cellular interactions between adipocytes and immune cells in adipose tissue have not been thoroughly elucidated. Recently, it has been demonstrated that adipocytes utilize lipid metabolites as a key mediator to initiate and mediate diverse adipose tissue immune responses. Adipocytes present lipid antigens and secrete lipid metabolites to determine adipose immune tones. In addition, the interactions between adipocytes and adipose immune cells are engaged in the control of adipocyte fate and functions upon metabolic stimuli. In this review, we discuss an integrated view of how adipocytes communicate with adipose immune cells using lipid metabolites. Also, we briefly discuss the newly discovered roles of adipose stem cells in the regulation of adipose tissue immunity.

scholarly journals Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

2018 ◽  
Vol 19 (10) ◽  
pp. 3240 ◽  
Author(s):  
Nicola Tempest ◽  
Alison Maclean ◽  
Dharani Hapangama
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Human Endometrium ◽  
Current Evidence ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Functional Layer ◽  
Almost All ◽  
Stromal Stem Cells

The human endometrium is a highly regenerative organ undergoing over 400 cycles of shedding and regeneration over a woman’s lifetime. Menstrual shedding and the subsequent repair of the functional layer of the endometrium is a process unique to humans and higher-order primates. This massive regenerative capacity is thought to have a stem cell basis, with human endometrial stromal stem cells having already been extensively studied. Studies on endometrial epithelial stem cells are sparse, and the current belief is that the endometrial epithelial stem cells reside in the terminal ends of the basalis glands at the endometrial/myometrial interface. Since almost all endometrial pathologies are thought to originate from aberrations in stem cells that regularly regenerate the functionalis layer, expansion of our current understanding of stem cells is necessary in order for curative treatment strategies to be developed. This review critically appraises the postulated markers in order to identify endometrial stem cells. It also examines the current evidence supporting the existence of epithelial stem cells in the human endometrium that are likely to be involved both in glandular regeneration and in the pathogenesis of endometrial proliferative diseases such as endometriosis and endometrial cancer.

scholarly journals Effects of degradable magnesium on paracrine signaling between human umbilical cord perivascular cells and peripheral blood mononuclear cells

2020 ◽  
Vol 8 (21) ◽  
pp. 5969-5983 ◽  
Author(s):  
Qian Wang ◽  
Lei Xu ◽  
Heike Helmholz ◽  
Regine Willumeit-Römer ◽  
Bérengère J. C. Luthringer-Feyerabend
Keyword(s):  
Stem Cells ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Human Mesenchymal Stem Cells ◽  
Human Umbilical Cord ◽  
Paracrine Signaling ◽  
Regenerative Processes ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Human mesenchymal stem cells (MSC) interact with numerous immune cells that can promote regenerative processes and influence inflammatory responses.

scholarly journals Dynamic secretome of bone marrow-derived stromal cells reveals a cardioprotective biochemical cocktail

2019 ◽  
Vol 116 (28) ◽  
pp. 14374-14383 ◽  
Author(s):  
Kshitiz ◽  
David D. Ellison ◽  
Yasir Suhail ◽  
Junaid Afzal ◽  
Laura Woo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Cell Types ◽  
Cardiac Cells ◽  
Therapeutic Effects ◽  
Paracrine Signaling ◽  
Context Specific ◽  
Analysis Platform ◽  
Stromal Stem Cells

Transplanted stromal cells have demonstrated considerable promise as therapeutic agents in diverse disease settings. Paracrine signaling can be an important mediator of these therapeutic effects at the sites of acute or persistent injury and inflammation. As many stromal cell types, including bone marrow-derived stromal cells (BMSCs), display tissue-specific responses, there is a need to explore their secretory dynamics in the context of tissue and injury type. Paracrine signals are not static, and could encode contextual dynamics in the kinetic changes of the concentrations of the secreted ligands. However, precise measurement of dynamic and context-specific cellular secretory signatures, particularly in adherent cells, remains challenging. Here, by creating an experimental and computational analysis platform, we reconstructed dynamic secretory signatures of cells based on a very limited number of time points. By using this approach, we demonstrate that the secretory signatures of CD133-positive BMSCs are uniquely defined by distinct biological contexts, including signals from injured cardiac cells undergoing oxidative stress, characteristic of cardiac infarction. Furthermore, we show that the mixture of recombinant factors reproducing the dynamics of BMSC-generated secretion can mediate a highly effective rescue of cells injured by oxidative stress and an improved cardiac output. These results support the importance of the dynamic multifactorial paracrine signals in mediating remedial effects of stromal stem cells, and pave the way for stem cell-inspired cell-free treatments of cardiac and other injuries.

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