Mesenchymal stem cells (MSC) are the non-hematopoietic stem cells with a multi-differentiation potentials, which has a low immunogenicity and immune regulation ability. MSC immune regulation ability is particularly important, such as MSC can inhibit the activation and proliferation of T, B lymphocytes, NK cells and dendritic cells (DC). Meanwhile, MSC is able to reconstruct the human hematopoietic microenvironment, improving the successful rate of hematopoietic stem cell transplantation. Graft versus host disease (GVHD) is the main factor causing hematopoietic stem cell transplantation-related mortality. Based on the above mentioned properties, MSCs are used to treat autoimmune diseases and GVHD, recently. Therefore, deep exploration of the cellular immune mechanisms of MSC to treat GVHD is particularly important. This review focuses on progress of research related to treatment of GVHD by MSC immune mechanisms and briefly summarizes the status of the clinical studies.
Graft vs Host Disease ; immunology ; therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; immunology

Mesenchymal stem cells (MSCs) are multipotent cells derived from many adult tissues, which can differentiate into cells of the mesodermal lineage, such as adipocyte, osteocyte and chondrocyte, as well as cells of other embryonic lineages. They are a promising tool for tissue engineering. In addition, MSC interacts with immune system, suppressing T cell, B cell and NK cell function and dendritic cell activities. MSC migrates to injured tissue to promote the survival of damaged cells and induces peripheral immune tolerance. The role of MSC in reducing the incidence and severity of graft versus host disease (GVHD) clinically has recently been reported. The immunoregulatory function of MSCs also shows a growing promise in the therapeutic application in autoimmune diseases. This review discusses the mechanism of MSC immunomodulatory ability and its therapeutic potential in autoimmune diseases.
Autoimmune Diseases ; surgery ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; immunology

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells possessing multi-differentiation potential, and were widely used in stem cell transplantation, tissue engineering, organ transplantation and immunotherapy, etc. However, the distribution and differentiation of MSCs after reinfusion directly influence their application. In this paper the "homing" characteristics, mechanisms and significance of MSCs were reviewed.
Cell Movement ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; immunology

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

Bone marrow mesenchymal stem cells (BM-MSC) have the characteristics of self-renewal and multipotency. They secrete a variety of cytokines and provided and ideal microenvironment for the division, proliferation and differentiation of hematopoietic stem cells (HSC) through the interaction with other stromal cells. Previous studies indicated that MSC could enhance engrafment and alleviate GVHD in allo-HSC and MSC co-transplantation. This effect on transplantation immunity may associate with escaping MHC compatible HSC from antigen recognition and suppressing activation and proliferation of nonspecific lymphocytes. In this paper, the characteristics of BM-MSC influencing transplantation immunity and its mechanism were reviewed.
Bone Marrow Cells ; cytology ; immunology ; Graft vs Host Disease ; immunology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; cytology ; immunology ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; immunology ; Transplantation Immunology

There has been an increasing interest in recent years on mesenchymal stem cell (MSC). It is well known that MSCs are capable of self-renewal and differentiating into many cell lineages. MSC can be expended to a large quantity that is required for clinical transplantation. Recent studies show that MSC have potential application in immune diseases due to their unique immunologic characteristics, such as low immunogenicity and immunoregulatory function. But their immunoregulatory mechanism is not yet clear. This review discusses the advances in researches on the mechanism of MSCs' immunoregulatory function and potential clinical application in immune disease and organ transplantation.
Animals ; B-Lymphocytes ; immunology ; Graft vs Host Disease ; immunology ; Humans ; Immune Tolerance ; immunology ; Immunotherapy ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; immunology ; T-Lymphocytes ; immunology

Objective To investigate the effect of adipose mesenchymal stem cells(AMSCs) on the peripheral blood lymphocyte(PBL) in psoriasis vulgaris(PV) patients and the expression and secretion profiles of related inflammatory cytokines in the PBL.Methods AMSCs from three PV patients were co-cultured with PBL. Peripheral blood regulatory cells(Treg) and T helper cell 17(Th17)ratio was measured by flow cytometry. The anti- and pro-inflammatory cytokines expressed and secreted by PBL were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA).Results The Treg/total lymphocyte ratio was significantly higher in the healthy people AMSCs+PBL co-culture group[(3.2±0.5)%;P=0.001],but AMSCs in patients had a tendency to promote the proliferation of Treg cells [(1.3±0.2)%],with no significant difference(P=0.485) when compared with the PBL culture alone group[(1.0±0.1)%]. qRT-PCR showed that the ability of PBL in expressing Treg transcription factor forkhead box p3 and transforming growth factor(TGF)-Β mRNA was significantly lower in psoriasis AMSCs+PBL co-culture group than in the healthy people AMSCs+PBL co-culture group(P=0.00,P=0.03),AMSCs had a tendency to promote the expression of interlukin(IL)-10 in peripheral blood lymphocytes,but there was no significant difference(P=0.09).ELISA showed the PBL in healthy people AMSCs+PBL co-culture group secreted the anti-inflammatory cytokine IL-10[(156.9±41.8) ng/Μl] and TGF-Β[(2774.1 ± 526.4) ng/Μl];in contrast,the abilities of PBL in PV patient AMSCs+PBL co-culture group in secreting the anti-inflammatory cytokines has a downward trend:IL-10[(90.4±28.8) ng/Μl] and TGF-Β[(1597.9±55.7) ng/Μl],although the differences were not statistically significant. After the co-culture,the proportion of Th17 cells in the psoriasis AMSCs+PBL co-culture group[(0.8±0.3)%] showed a decreasing trend when compared with the PBL culture alone group[(1.1±0.1)%],although the results were not statistically significant. Also,the proportion of Th17 cells showed no significant difference between PV patient AMSCs+PBL co-culture group and healthy people AMSCs+PBL co-culture group. Finally,both the psoriasis AMSCs+PBL co-culture group and the healthy people AMSCs+PBL co-culture group showed no obvious inhibitory effect on the expression and secretion of Th17 transcription factor retinoid-related orphan nuclear receptor Γt and pro-inflammatory cytokines IL-17 and IL-23 in PBL,and there was no significant difference between these two groups.Conclusions AMSCs in PV patients have decreased ability in regulating the anti-inflammatory function of peripheral blood Treg lymphocytes. However,they have no effect on the proinflammatory effect of peripheral blood Th17 lymphocytes.
Adipose Tissue ; cytology ; Cytokines ; immunology ; Forkhead Transcription Factors ; immunology ; Humans ; Inflammation ; immunology ; Mesenchymal Stem Cells ; cytology ; Psoriasis ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., "subtotipotent stem cell" hypothesis, MSC system, and "Yin and Yang" balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database ( http://clinicaltrials.gov ) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.
Cell Differentiation ; Humans ; Immune System Diseases ; immunology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; immunology ; physiology ; Randomized Controlled Trials as Topic ; Regenerative Medicine

Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications.
Animals ; *Cellular Microenvironment ; Humans ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology/immunology/*metabolism ; Regenerative Medicine/*methods

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
Humans ; B7-H1 Antigen/metabolism* ; Mesenchymal Stem Cells/immunology* ; T-Lymphocytes/metabolism* ; Immunomodulation