The immunoregulatory effects of mescenchymal stem cell (MSC) and its application have become a hot research topic in recent years. This article reviews the up-to-dated research advances in the features and mechanisms of immune regulation of MSC and its application.
Animals ; Humans ; Lymphocyte Subsets ; immunology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; physiology ; T-Lymphocytes, Regulatory ; immunology

The study was aimed to compare the effects of T-cell suppression mediated by mesenchymal stem cells (MSC) from normal individuals and myelodysplastic syndromes (MDS) patients. MSC were cultured from the bone marrow of 12 healthy volunteers and 12 MDS patients, the morphology, surface markers and expression of several cytokines of MSC from normal individuals and MDS patients were compared, and the effects of T-cell suppression were tested in the following assays: phytohemaglutinin (PHA)-primed cultures, mixed lymphocyte reaction (MLR), cell cycle of T-cell after PHA-primed cultures and apoptosis of T-cell as well. The results showed that the MSC from normal individuals and MDS patients were similar in morphology, proliferation and surface markers. The suppressions of T-cell proliferation induced by PHA and alloantigens mediated by MDS-MSC were significantly lower than that of normal MSC. More T-cells were arrested in G0/G1 phase by normal MSC, while the effects were deficient by MDS-MSC. The suppression of T-cell activation mediated by MDS-MSC was also lower than that of normal MSC, but suppression effect on T-cell apoptosis increased. The cytokines TGF-beta1, 3, FasL expressed by MDS-MSC were reduced as compared with normal MSC, but TGF-beta2 expression increased in MDS-MSC. It is concluded that although the morphology, proliferation and cell surface markers of MDS-MSC are normal, the T-cell suppression mediated by MDS-MSC is deficient as compared with normal controls. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined.
Adult ; Aged ; Bone Marrow Cells ; cytology ; physiology ; Female ; Humans ; Immune Tolerance ; immunology ; physiology ; Male ; Mesenchymal Stromal Cells ; immunology ; physiology ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; pathology ; T-Lymphocytes ; immunology

Mesenchymal stem cells have generated great interest among researchers and physicians due to their unique biological characteristics and potential clinical applications. Here, I propose for the first time the concept of a hierarchical system which is composed of all mesenchymal stem cells from post-embryonic subtotipotent stem cells to MSC progenitors. Post-embryonic subtotipotent stem cells are left-over cells during embryonic development and are on the top of the hierarchy. MSC system is a combination of cells that are derived from different stages of embryonic development, possess different differentiation potential and ultimately give rise to cells that share a similar set of phenotypic markers. The concept of MSC system has important implications: (1) it entirely explains the three important biological characteristics of MSC: stem cell properties of MSC, MSC as components of tissue microenvironment and immunomodulatory functions of MSC. (2) It balances immune responses and tissue metabolism. (3) It could provide tissue-specific stem cells for clinical application with high efficiency and safety. In a word, this concept constitutes an important part of the biological properties of MSC and will help researchers gain better insight into MSC.
Cell Differentiation ; Cellular Microenvironment ; Humans ; Immunomodulation ; Mesenchymal Stromal Cells ; immunology ; physiology ; Phenotype

Mesenchymal stem cells (MSCs) are a kind of adult stem cells which have the capability to differentiate into multiple cell types as well as self-renew continuously. Recent studies demonstrate that MSCs are low immunogenic and able to exert immunomodulatory function by various approaches, such as suppression of the lymphocyte proliferation, reduction of the dentritic cell generation, maturation and function, down-regulation of the CTL formation and enhancement of regulatory T-cell proportion. In vivo experiments show that MSC infusion can prolong the survival time of allo-skin graft in baboon and ameliorate experimental autoimmune encephalomyelitis in mice. Successful reports have been documented about clinical application of MSC in the management of graft-versus-host disease. In this review, the immunological characteristics and the immunomodulation functions in vitro and in vivo of MSC were summarized.
Animals ; Graft vs Host Disease ; prevention & control ; Humans ; Immunomodulation ; physiology ; Mesenchymal Stromal Cells ; immunology ; physiology ; T-Lymphocytes, Regulatory ; immunology

The defectiveness of bone marrow mesenchymal stem cells (BM-MSCs) in acquired aplastic anemia (AA) has been a frequent research topic in recent years. This review summarizes the defectiveness of BM-MSCs which is responsible for the mechanism of acquired AA and the prospective application of BM-MSCs in the treatment of acquired AA. An increasingly number of laboratory statistics has demonstrated that the defectiveness of BM-MSCs is more likely to play an important role in the pathogenesis of AA, namely, the apparently different biological characteristics and gene expression profiles, the decreased ability of supporting hematopoiesis as well as self-renewal and differentiation, and the exhaustion of regulating immune response of hematopoietic environment. Those abnormalities continuously prompt AA to become irreversible bone marrow failure along with the imbalanced immunity. With deepening research on MSCs, infusion of MSCs for the primary purpose of recovering hematopoietic microenvironment may become a new approach for the treatment of AA.
Anemia, Aplastic ; etiology ; immunology ; therapy ; Bone Marrow ; Cell Differentiation ; Cell Proliferation ; Cytokines ; analysis ; Humans ; Lymphocyte Activation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; physiology ; T-Lymphocytes, Regulatory ; immunology

This study was purposed to investigate the immunoregulatory effect of endothelial cells derived from mesenchymal stem cells (MSC). The human MSC was induced to differentiate into endothelial cells for one week. The phenotypes were evaluated by flow cytometry, the cell morphologic feature was observed by invert phase-contrast microscope and analysis of capillary formation was performed by using the in vitro angiogenesis kit. The immunoregulatory effect was detected by lymphocyte transformation test. The result indicated that during the differentiation cells grew fast and there was no significant change in the phenotypes, i.e. CD73, CD105, HLA-ABC were positive and CD34, CD80, CD86, HLA-DR, CD31 were negative. Immunofluorescence analysis showed typical expression of the von Willebrand factor. Differentiated MSCs formed capillary-like structure. Endothelial cells derived from MSC also revealed immunosuppressive effect on T cell proliferation in a dose-dependent manner. It is concluded that endothelial cells derived from MSC also harbor immunoregulatory effect on T lymphocytes.
5'-Nucleotidase ; metabolism ; Cell Differentiation ; physiology ; Cells, Cultured ; Child ; Endothelial Cells ; cytology ; immunology ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; T-Lymphocytes ; immunology ; von Willebrand Factor ; metabolism

This study was aimed to investigate if human heart harbored a population of primitive undifferentiated cells with the characteristics of MPC. Cells were isolated from human fetal heart and were cultured under conditions appropriate for bone marrow-derived MPCs. Their morphology, phenotypes and functions were tested by methods developed for MPC from other sources. The results showed that morphologically, cells were spindle shaped and resembled fibroblasts. In their undifferentiated state, cells were CD73, CD105, CD29, CD44, HLA-ABC, CD166 positive and CD45, CD34, CD86, HLA-DR negative. When cultured in adipogenic, osteogenic or chondrogenic media, cells differentiated into adipocytes, osteocytes and chondrocytes respectively. They could be extensively expanded in vitro and exhibited very low immunogenicity as evaluated by T cell proliferation assays. It is concluded that cells isolated from fetal heart possess similarity to their adult and fetal bone marrow counterparts in morphologic, immunophenotypic, and functional characteristics.
Bone Marrow Cells ; cytology ; Cell Adhesion ; Cell Differentiation ; Cells, Cultured ; Fetal Heart ; cytology ; Fetus ; Humans ; Mesenchymal Stromal Cells ; cytology ; immunology ; Multipotent Stem Cells ; physiology

The aim of this study was to explore effect of CD8+CD28- T-lymphocyte in the inhibition of mesenchymal stem cells (MSC) on T-lymphocyte proliferation. T cells were harvested by using nylon column and CD8+ T cells were sorted by magnetic beads; the T-lymphocyte proliferation in the presence of PHA was evaluated by MTT; the proportion of CD8+CD28- T cells was assayed by fluorescence-activated cell sorter (FACS). The results showed that MSC inhibited T-lymphocyte proliferation and the inhibitory effect depended on the amount of MSC; the data of FACS indicated that in the CD8+ T cells co-cultured with MSC, CD8+CD28- T cells were up-regulated significantly, compared with the non-treated CD8+ T cells. In conclusion, MSC perform their immunosuppressive function by up-regulation of CD8+CD28- T cells.
Bone Marrow Cells ; physiology ; CD28 Antigens ; analysis ; CD8 Antigens ; analysis ; Humans ; Lymphocyte Activation ; Mesenchymal Stromal Cells ; physiology ; T-Lymphocyte Subsets ; immunology ; Up-Regulation

Mesenchymal stem cells have two main properties: self renewal and the ability to differentiate multiple lineage. Because MSCs exhibit low immunogenicity and demonstrate significant suppressive activity in cell cultures containing alloreactive T cells, they play an important role in transplantation immunology, but the exact mechanism remains unknown. This article focuses on the immunoregulatory feature of MSCs to immunoeffector cells, such as T cells, B cells, and NK cells. The role of MSC in transplantation immunoregulation, regulatory mechanism of MSC in cellular immunity (direct contact of cells with cells, apoptosis and immunoregulation of MSC on lymphocytes), immunoregulation of MSC on DC and NK cells were reviewed.
Animals ; Cell Communication ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Humans ; Killer Cells, Natural ; cytology ; immunology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; physiology ; Signal Transduction ; T-Lymphocytes ; cytology ; immunology

OBJECTIVETo explore the effect of mouse bone marrow mesenchymal stem cells (MSCs) on the expression of chemokine receptors in T lymphocytes in vitro.

METHODSMouse bone marrow MSCs were separated with Percoll, cultured and expanded in low glucose DMEM. C57BL/6 mouse spleenocytes were cultured in the 24-hole flasks by the density of 1 x10(6)/hole. Phytohemagglutinin (PHA) was then added to the holes and cultured for 72 hrs. This study consisted of three groups. Groups A and B were co-cultured by adding MSCs as the ratio of 0.1 and 0.01 to spleenocytes respectively. The control group was cultured without MSCs. Three days later the suspended spleenocytes were harvested for detecting the expression of three chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes by the flow cytometry.

RESULTSThe expression of CD3(+)CCR5(+) and CD3(+)CCR7(+) were statistically different among the three groups. Group A had the strongest expression, followed by group B and the control group. The expression of CD3(+)CXCR3(+) in group A was statistically higher than that in group B and the control group.

CONCLUSIONSMSCs could up-regulate the expression of chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes stimulated by PHA.

Animals ; Bone Marrow Cells ; physiology ; Cells, Cultured ; Lymphocyte Activation ; Mesenchymal Stromal Cells ; physiology ; Mice ; Mice, Inbred C57BL ; Phytohemagglutinins ; pharmacology ; Receptors, CCR5 ; analysis ; Receptors, CCR7 ; analysis ; Receptors, CXCR3 ; analysis ; Spleen ; cytology ; immunology ; T-Lymphocytes ; immunology