scholarly journals Immunosuppressant Drugs Mitigate Immune Responses Generated by Human Mesenchymal Stem Cells Transplanted into the Mouse Parenchyma

2021 ◽  
Vol 30 ◽  
pp. 096368972110190
Author(s):  
Jung Won Hwang ◽  
Su Hyeon Myeong ◽  
Na-Hee Lee ◽  
Hyeongseop Kim ◽  
Hyo Jin Son ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Immune Surveillance ◽  
Human Mesenchymal Stem Cells ◽  
Immunohistochemical Analysis ◽  
Human Mscs ◽  
Cast Doubt ◽  
Study Support ◽  
High Infiltration

It has been widely accepted that mesenchymal stem cells (MSCs) can evade the immune surveillance of the recipient. However, emerging research cast doubt on whether MSCs are intrinsically immune-privileged. Previously, we observed that the transplantation of human MSCs (hMSCs) into the mouse parenchyma attracted a high infiltration of leukocytes into the injection tract. Thus, in order to reduce the immune responses generated by hMSCs, the aim of this study was to assess which immunosuppressant condition (dexamethasone only, tacrolimus only, or dexamethasone and tacrolimus together) would not only reduce the overall immune response but also enhance the persistence of MSCs engrafted into the caudate putamen of wild-type C57BL/6 mice. According to immunohistochemical analysis, compared to the hMSC only group, the administration of immunosuppressants (for all three conditions) reduced the infiltration of CD45-positive leukocytes and neutrophils at the site of injection. The highest hMSC persistence was detected from the group that received combinatorial administrations of dexamethasone and tacrolimus. Moreover, compared to the immunocompetent WT mouse, higher MSC engraftment was observed from the immunodeficient BALB/c mice. The results of this study support the use of immunosuppressants to tackle MSC-mediated immune responses and to possibly prolong the engraftment of transplanted MSCs.

scholarly journals Preconditioning of Human Mesenchymal Stem Cells to Enhance Their Regulation of the Immune Response

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Arman Saparov ◽  
Vyacheslav Ogay ◽  
Talgat Nurgozhin ◽  
Medet Jumabay ◽  
William C. W. Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Human Mesenchymal Stem Cells ◽  
Regulatory Function ◽  
Harsh Environment ◽  
Human Mscs

Mesenchymal stem cells (MSCs) have attracted the attention of researchers and clinicians for their ability to differentiate into a number of cell types, participate in tissue regeneration, and repair the damaged tissues by producing various growth factors and cytokines, as well as their unique immunoprivilege in alloreactive hosts. The immunomodulatory functions of exogenous MSCs have been widely investigated in immune-mediated inflammatory diseases and transplantation research. However, a harsh environment at the site of tissue injury/inflammation with insufficient oxygen supply, abundance of reactive oxygen species, and presence of other harmful molecules that damage the adoptively transferred cells collectively lead to low survival and engraftment of the transferred cells. Preconditioning of MSCsex vivoby hypoxia, inflammatory stimulus, or other factors/conditions prior to their use in therapy is an adaptive strategy that prepares MSCs to survive in the harsh environment and to enhance their regulatory function of the local immune responses. This review focuses on a number of approaches in preconditioning human MSCs with the goal of augmenting their capacity to regulate both innate and adaptive immune responses.

scholarly journals Effect of alternan versus chitosan on the biological properties of human mesenchymal stem cells

RSC Advances ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 4370-4379 ◽  
Author(s):  
Thanapon Charoenwongpaiboon ◽  
Kantpitchar Supraditaporn ◽  
Phatchanat Klaimon ◽  
Karan Wangpaiboon ◽  
Rath Pichyangkura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Biological Properties ◽  
Human Mscs

Alternan α-1,3- and α-1,6-linked glucan, promotes proliferation, migration, and differentiation of human MSCs.

scholarly journals Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem Cells (hMSCs) Engraftment in NOD/SCID Mice following Irradiation

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Sabine François ◽  
Benoit Usunier ◽  
Luc Douay ◽  
Marc Benderitter ◽  
Alain Chapel
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Total Body Irradiation ◽  
Human Mesenchymal Stem Cells ◽  
Scid Mice ◽  
Human Mscs ◽  
Long Term Treatment ◽  
Total Body

There is little information on the fate of infused mesenchymal stem cells (MSCs) and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs) intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice submitted to total body irradiation (TBI) or local irradiation (abdominal or leg irradiation). The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR). Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.

scholarly journals Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Yu Zhang ◽  
Dilaware Khan ◽  
Julia Delling ◽  
Edda Tobiasch
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Human Mscs ◽  
Industrialized Countries ◽  
Tight Control ◽  
Age Related ◽  
Donor Cells ◽  
Immunosuppressive Microenvironment

Human mesenchymal stem cells (hMSCs) are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient’s body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.

Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 4120-4126 ◽  
Author(s):  
Xiao-Xia Jiang ◽  
Yi Zhang ◽  
Bing Liu ◽  
Shuang-Xi Zhang ◽  
Ying Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Human Mesenchymal Stem Cells ◽  
Interleukin 4 ◽  
Human Mscs ◽  
Gm Csf ◽  
Macrophage Colony ◽  
And Function

AbstractMesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.

scholarly journals Human mesenchymal stem cells are resistant to UV-B irradiation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ramon Lopez Perez ◽  
Jannek Brauer ◽  
Alexander Rühle ◽  
Thuy Trinh ◽  
Sonevisay Sisombath ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
P53 Protein ◽  
Human Mesenchymal Stem Cells ◽  
Clonogenic Survival ◽  
Cellular Adhesion ◽  
Dermal Fibroblasts ◽  
Human Mscs ◽  
Skin Damage ◽  
Skin Injuries

AbstractAlbeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage. While multipotent mesenchymal stem cells (MSCs) may aid the regeneration of UV-B-induced skin injuries, the influence of UV-B irradiation on MSCs remains widely unknown. Here, we show that human MSCs are relatively resistant to UV-B irradiation compared to dermal fibroblasts. MSCs exhibited higher clonogenic survival, proliferative activity and viability than dermal fibroblasts after exposure to UV-B irradiation. Cellular adhesion, morphology and expression of characteristic surface marker patterns remained largely unaffected in UV-irradiated MSCs. The differentiation ability along the adipogenic, osteogenic and chondrogenic lineages was preserved after UV-B treatment. However, UV-B radiation resulted in a reduced ability of MSCs and dermal fibroblasts to migrate. MSCs exhibited low apoptosis rates after UV-B irradiation and repaired UV-B-induced cyclobutane pyrimidine dimers more efficiently than dermal fibroblasts. UV-B irradiation led to prolonged p53 protein stability and increased p21 protein expression resulting in a prolonged G2 arrest and senescence induction in MSCs. The observed resistance may contribute to the ability of these multipotent cells to aid the regeneration of UV-B-induced skin injuries.

scholarly journals SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Botti Chiara ◽  
Caiafa Ilaria ◽  
Coppola Antonietta ◽  
Cuomo Francesca ◽  
Miceli Marco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Therapeutic Angiogenesis ◽  
Induced Response ◽  
Human Mscs ◽  
Hypoxic Conditions ◽  
And Migration

Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types. Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders. However, the molecular mechanisms underlying these effects remain unclear. A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function. Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions. Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level. We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level. Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis. Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs. Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.

Preparation of inorganic-organic hybrid membrane for peripheral nerve reconstruction

2013 ◽  
Vol 2013 (CICMT) ◽  
pp. 000173-000176
Author(s):  
Yuki Shirosaki ◽  
Satoshi Hayakawa ◽  
Akiyoshi Osaka ◽  
Maria A. Lopes ◽  
José D. Santos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Nerve ◽  
Functional Recovery ◽  
Human Mesenchymal Stem Cells ◽  
Hybrid Membrane ◽  
Human Mscs ◽  
Hybrid Membranes ◽  
Nerve Reconstruction ◽  
Porous Chitosan

The treatment of peripheral nerve injuries is still one of the most challenging tasks in neurosurgery, as functional recovery is rarely satisfactory in these patients. The concept behind the use of biodegradable nerve guides is that no foreign material should be left in place after the device has fulfilled its task, so as to spare a second surgical intervention. In a previous study, flexible and biodegradable chitosan-3-glycidoxypropyltrimethoxysilane (GPTMS) hybrid membranes exhibited better cytocompatibility in terms of osteoblastic cells than chitosan membrane. Porous chitosan hybrid membranes, derived by freeze-drying the hybrid gels, showed that the cells were attached and proliferated both on the surface and into pores. In this study, the porous chitosan-silicate hybrid membranes with non-differentiated human mesenchymal stem cells isolated from Wharton's jelly of umbilical cord were used to reconstruct the crushed peripheral nerve. Axonotmesis lesion of 3 mm was enwrapped with the hybrid membranes with or without a monolayer of non-differentiated human mesenchymal stem cells. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks. The combination of hybrid membranes and human MSCs infiltration showed a slightly better recovery than the untreated control (the just crushed nerve). On the other hand, the hybrid membrane alone promoted the crushed peripheral nerve reconstruction. It is expected that the porous chitosan hybrid membranes is candidate for the clinical tool in peripheral nerve reconstructive surgery.

scholarly journals Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma

2006 ◽  
Vol 203 (5) ◽  
pp. 1235-1247 ◽  
Author(s):  
Aarif Y. Khakoo ◽  
Shibani Pati ◽  
Stasia A. Anderson ◽  
William Reid ◽  
Mohamed F. Elshal ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Kaposi's Sarcoma ◽  
Human Mesenchymal Stem Cells ◽  
Kaposi’S Sarcoma ◽  
Stem Cell Population ◽  
Cell Contact ◽  
Human Mscs

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell–cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt.

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