scholarly journals Regulatory Effect of Mesenchymal Stem Cells on T Cell Phenotypes in Autoimmune Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Zhiping Wei ◽  
Jintao Yuan ◽  
Gaoying Wang ◽  
Dickson Kofi Wiredu Ocansey ◽  
Zhiwei Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Tissue Repair ◽  
T Cell Subsets ◽  
Autoimmune Conditions ◽  
T Cell Phenotypes ◽  
Cell Phenotypes

Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.

Abstract 13: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yanqing Gong ◽  
Jane Hoover-Plow ◽  
Ying Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tissue Repair ◽  
Critical Role ◽  
Cardiac Repair ◽  
Internal Diameter ◽  
Hematopoietic Stem

Ischemic heart disease, including myocardial infarction (MI), is the primary cause of death throughout the US. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms regulating G-CSF-induced cardiac repair may offer novel approaches for strengthening stem cell-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated cardiac repair after MI. Our data show that G-CSF significantly improves cardiac tissue repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue repair and heart function by G-CSF is observed in Plg -/- mice, indicating that Plg is required for G-CSF-regulated cardiac repair after MI. To investigate whether Plg regulates HPSC recruitment to ischemia area, bone marrow transplantion (BMT) with EGFP-expressing BM cells was performed to visualize BM-derived stem cells in infarcted tissue. Our data show that G-CSF dramatically increases recruitment of GFP+ cells (by 16 fold) in WT mice but not in Plg -/- mice, suggesting that Plg is essential for HPSC recruitment from BM to the lesion sites after MI. In further studies, we investigated the role of Plg in the regulation of SDF-1/CXCR-4 axis, a major regulator for HPSC recruitment. Our results show that G-CSF significantly increases CXCR-4 expression in infarcted area in WT mice. While G-CSF-induced CXCR-4 expression is markedly decreased (80%) in Plg -/- mice, suggesting Plg may regulate CXCR-4 expression during HSPC recruitment to injured heart. Interestingly, Plg does not affect SDF-1 expression in response to G-CSF treatment. Taken together, our findings have identified a critical role of Plg in HSPC recruitment to the lesion site and subsequent tissue repair after MI. Thus, targeting Plg may offer a new therapeutic strategy to improve G-CSF-mediated cardiac repair after MI.

Immunosupressive Property of Mesenchymal Stem Cells (MSCs) in Mixed Lymphocyte Reactions In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4313-4313 ◽  
Author(s):  
Jianyong Li ◽  
Lijuan Meng ◽  
Yu Zhu ◽  
Hua Lu ◽  
Changgeng Ruan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Bone Marrow Mscs ◽  
Human Bone Marrow Mscs ◽  
Mixed Lymphocyte Reactions ◽  
Activation Phase

Abstract Meesnchymal stem cells (MSCs) were successfully used in the prevention and treatment of graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. To further explore the immunosuppressive property of human bone marrow (MSCs) in alloantigen-induced mixed lymphocyte reactions (MLRs) in vitro, human bone marrow MSCs and lymphocytes were prepared from healthy volunteers. MSCs were expanded in vitro in Mesencult serum free media. MSCs were cocultured with one-way MLRs and bidirectional MLRs, responder cells were labeled with carboxyfluorescein diacetate- succinimidyl ester (CFSE) in bidirectional MLRs. Cell Counting Kit-8(CCK-8)kit was used in cell proliferation detection, T-cell subsets were analyzed by flow cytometry (FCM). The results showed that MSCs were positive for CD105, CD73, CD13, CD90 and were negative for hematopoietic cell markers. In one-way MLRs, MSCs down-regulated alloantigen-induced lymphocyte expansion in a dose-dependent and MHC-independend manner. In two-way MLRs, MSCs suppressed proliferation of CFSE positive cells. T cell subsets were changed: Th2 and Tc2 were down-regulated. Th2 was reduced from 1.70% to 0.65%, and Tc2 reduced from 1.10% to 0.47%, while Th1 and Tc1 were unaffected. T cells that became CD69+, which was an early activation marker, were significantly up-regulated from 7.14% to 26.12% and CD4+CD25+T regulatory cells (CD4+CD25+Tr) were up-regulated from 4.04% to 6.19%, which indicating that suppression did not interfere with activation phase of T cells and might be mediated by CD4+CD25+Tr partly. We conclede that MSCs down-regulated alloantigen-induced lymphocyte expansion. The immunosupressive effect might involve in post-activation phase of T cells. CD4+CD25+Tr might contribute to the suppressory activity of MSCs.

Loss of Gfi1 Impedes Development of T-Cell Lymphoma upon Exposure to N-ethyl-N-nitrosourea but Predisposes to Severe Myleodysplastic Changes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2221-2221
Author(s):  
Cyrus Khandanpour ◽  
Ulrich Duehrsen ◽  
Tarik Möröy
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Dna Damage ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Cell Lymphoma ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Deficient Mice

Abstract Exogenous toxic substances often cause the initiation and development of leukemia and lymphoma by acting as mutagens. N-ethyl-N-nitrosourea (ENU) is a paradigmatic example for such a substance, which introduces point mutations in the genome through DNA damage and repair pathways. ENU is widely used to experimentally induce T-cell lymphomas in mice. We have used ENU to investigate whether the hematopoietic transcription factor Gfi1 is required for lymphomagenesis. The Gfi1 gene was originally discovered as a proviral target gene and a series of experiments with transgenic mice had suggested a role of Gfi1 as a dominant oncogene with the ability to cooperate with Myc and Pim genes in the generation of T-cell lymphoma. In addition, Gfi1 deficient mice showed a defect in T-cell maturation but also aberration in myeloid differentiation and an accumulation of myelomonocytic cells. ENU was administered i.p. once a week for three weeks with a total dose of 300mg/kg to wild type (wt) and Gfi1 null mice. Wild type mice (12/12) predominantly developed T-cell tumors and rarely acute myeloid leukemia, as expected. However, only 2/8 Gfi1 −/− mice succumbed to lymphoid neoplasia; they rather showed a severe dysplasia of the bone marrow that was more pronounced than in wt controls. These changes in Gfi1 null mice were accompanied by a dramatic decrease of the LSK (Lin-, Sca1- and c-Kit+) bone marrow fraction that contains hematopoietic stem cells and by a higher percentage (18%) of bone marrow cells, not expressing any lineage markers (CD4, CD 8, Ter 119, Mac1, Gr1, B220, CD3). In particular, we found that the LSK subpopulation of Gfi1 deficient mice showed a noticeable increase in cells undergoing apoptosis suggesting a role of Gfi1 in hematopoietic stem cell survival. In addition, Gfi1−/− bone marrow cells and thymic T-cells were more sensitive to DNA damage such as radiation and exposure to ENU than their wt counterparts pointing to a role of Gfi1 in DNA damage response. Our results indicate that Gfi1 is required for development of T-cell tumors and that a loss of Gfi1 may sensitize hematopoietic cells and possibly hematopoietic stem cells for programmed cell death. Further studies have to show whether interfering with Gfi1 expression or function might represent a tool in the therapy of leukemia.

scholarly journals Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells on Mouse Bone-Marrow-Derived Dendritic Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Minhwa Park ◽  
Yu-Hee Kim ◽  
Jung-Hwa Ryu ◽  
So-Youn Woo ◽  
Kyung-Ha Ryu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Subsets ◽  
Regulatory Function ◽  
Mouse Bone Marrow ◽  
And Function

Mesenchymal stem cells (MSCs) are considered valuable sources for cell therapy because of their immune regulatory function. Here, we investigated the effects of tonsil-derived MSCs (T-MSCs) on the differentiation, maturation, and function of dendritic cells (DCs). We examined the effect of T-MSCs on differentiation and maturation of bone-marrow- (BM-) derived monocytes into DCs and we found suppressive effect of T-MSCs on DCs via direct contact as well as soluble mediators. Moreover, T cell proliferation, normally increased in the presence of DCs, was inhibited by T-MSCs. Differentiation of CD4+T cell subsets by the DC-T cell interaction also was inhibited by T-MSCs. The soluble mediators suppressed by T-MSCs were granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Taken together, T-MSCs exert immune modulatory function via suppression of the differentiation, maturation, and function of BM-derived DCs. Our data suggests that T-MSCs could be used as a novel source of stem cell therapy as immune modulators.

scholarly journals The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction

2020 ◽  
Vol 21 (14) ◽  
pp. 5013
Author(s):  
Tabito Kino ◽  
Mohsin Khan ◽  
Sadia Mohsin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
T Cell ◽  
Inflammatory Response ◽  
Stem Cell Transplantation ◽  
Immune Cells ◽  
Tissue Repair ◽  
Ischemic Injury ◽  
T Cell Subsets

Ischemic injury to the heart causes cardiomyocyte and supportive tissue death that result in adverse remodeling and formation of scar tissue at the site of injury. The dying cardiac tissue secretes a variety of cytokines and chemokines that trigger an inflammatory response and elicit the recruitment and activation of cardiac immune cells to the injury site. Cell-based therapies for cardiac repair have enhanced cardiac function in the injured myocardium, but the mechanisms remain debatable. In this review, we will focus on the interactions between the adoptively transferred stem cells and the post-ischemic environment, including the active components of the immune/inflammatory response that can mediate cardiac outcome after ischemic injury. In particular, we highlight how the adaptive immune cell response can mediate tissue repair following cardiac injury. Several cell-based studies have reported an increase in pro-reparative T cell subsets after stem cell transplantation. Paracrine factors secreted by stem cells polarize T cell subsets partially by exogenous ubiquitination, which can induce differentiation of T cell subset to promote tissue repair after myocardial infarction (MI). However, the mechanism behind the polarization of different subset after stem cell transplantation remains poorly understood. In this review, we will summarize the current status of immune cells within the heart post-MI with an emphasis on T cell mediated reparative response after ischemic injury.

The role of T cell phenotypes in decreased lymphoproliferation of the elderly

1989 ◽  
Vol 50 (1) ◽  
pp. 82-99 ◽  
Author(s):  
Deborah Matour ◽  
Meryle Melnicoff ◽  
Donald Kaye ◽  
Donna M. Murasko
Keyword(s):  
T Cell ◽  
The Elderly ◽  
T Cell Phenotypes ◽  
Cell Phenotypes

scholarly journals Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hussein A. Abbas ◽  
Dapeng Hao ◽  
Katarzyna Tomczak ◽  
Praveen Barrodia ◽  
Jin Seon Im ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Single Cell ◽  
T Cell Receptor ◽  
Myeloid Leukemia ◽  
Cell Receptor ◽  
T Cell Phenotypes ◽  
Cell Phenotypes ◽  
Acute Myeloid

AbstractIn contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8+ cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy-resistant patients. Trajectory analysis reveals a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8+ T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.

Sign in / Sign up

Export Citation Format

Share Document