Cellular Therapy with Donor Mesenchymal Stem Cells Combined with Co-Stimulation Blockade Prolongs Solid Organ Allograft Survival.

Background: Normothermic Machine Perfusion (NMP) has been established in the field of solid organ transplantation for both liver and kidney allografts. The ability to perfuse organs at body temperature enables viability assessment as well as optimisation prior to implantation. Discussion: A recent in vitro report of the use of Mesenchymal Stem Cells (MSCs) in the use of a normothermic lung perfusion circuit has raised the possibility of their use in solid organ transplantation. The aim of this short review is to outline the potential uses of bone marrow derived MSCs for their use in renal allograft ex vivo NMP. An overview is provided of current literature of NMP as well as theorised uses for MSCs.

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Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γModified Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2017/1025820 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 10

Author(s):

Kisha Nandini Sivanathan ◽

Darling Rojas-Canales ◽

Shane T. Grey ◽

Stan Gronthos ◽

Patrick T. Coates

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

T Cell ◽

Antigen Processing ◽

Cellular Therapy ◽

Human Mesenchymal Stem Cells ◽

Humoral Response ◽

Transcriptome Profiling ◽

Antigen Processing And Presentation ◽

Immunomodulatory Function

Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.

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Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation

Transplant International ◽

10.1111/j.1432-2277.2008.00786.x ◽

2009 ◽

Vol 22 (4) ◽

pp. 365-376 ◽

Cited By ~ 60

Author(s):

Meindert Crop ◽

Carla Baan ◽

Willem Weimar ◽

Martin Hoogduijn

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Organ Transplantation ◽

Immune Therapy ◽

Solid Organ Transplantation ◽

Solid Organ

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A new cellular therapy using soluble RAGE overexpressing-mesenchymal stem cells in a rat model of osteoarthritis

Cytotherapy ◽

10.1016/j.jcyt.2018.03.009 ◽

2018 ◽

Vol 20 (5) ◽

pp. e3

Author(s):

J. Baek ◽

M. Park ◽

S. Kim ◽

M. Cho

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Rat Model ◽

Cellular Therapy ◽

Soluble Rage

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Human Mesenchymal Stem Cells Inhibit In Vitro Antibody Production Against Alloantigens.

Blood ◽

10.1182/blood.v106.11.3033.3033 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3033-3033

Author(s):

Patrizia Comoli ◽

Rita Maccario ◽

Maria Antonietta Avanzini ◽

Fabrizio Ginevri ◽

Antonia Moretta ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

B Cell ◽

Antibody Production ◽

Third Party ◽

Favourable Effect ◽

Solid Organ ◽

Hematopoietic Stem ◽

Cross Match

Abstract Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation. In particular, this humoral response unfavorably affects the outcome of solid organ transplantation, and it has been hypothesized to be responsible for some of the clinical manifestations related to graft-versus-host disease (GVHD). In detail, the presence of antibodies against donor cells is a contraindication to kidney transplantation because of the risk of hyperacute rejection. In the effort to expand the donor pool, trials of allograft transplantation across HLA-sensitization have been conducted by means of strategies including pre-transplant plasmapheresis, intravenous immunoglobulins (Ig), anti-B cell monoclonal antibodies and splenectomy, associated with high-intensity immunosuppressive regimens. These measures have proved only partially successful in preventing humoral rejection in high-risk patients. Thus, the development of new therapeutic tools able to blunt alloantibody production could be a welcomed implementation to existing protocols. Mesenchymal stem cells (MSC) have been demonstrated to possess immunomodulatory capacity, since they induce T-cell hyporesponsiveness in vitro, prolong survival of skin graft in a primate model, and seem to decrease GVHD incidence and severity in humans given hematopoietic stem cell transplantation. To verify whether MSC may exert an inhibitory effect on antibody production, we stimulated B-cell-enriched peripheral blood mononuclear cells (PBMC) obtained from healthy controls (n=9) or sensitized prospective kidney recipients (n=5) in a mixed lymphocyte culture (MLC) against irradiated HLA-disparate stimulator PBMC (controls) or stimulators cells bearing HLA antigens matched with the positive cross-match (patients). Antibody production in the absence or in the presence of third-party allogeneic MSC (responder:MSC ratio:4:1) was then evaluated by ELISA. We found that the addition of MSC at the beginning of MLC considerably inhibited IgG and IgM production (median fold-decrease of IgG production: controls, 7; patients, 5; median fold-decrease of IgM production: controls, 17; patients, 4). Our preliminary findings indicate that third-party MSC are able to suppress antibody production in vitro, and may therefore help to overcome a positive cross-match in sensitized transplant recipients. These results may also contribute to partly explain the mechanism at the basis of the favourable effect played by MSC in patients with GVHD.

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Mobilised Peripheral Blood Could Be a Suitable Source of Mesenchymal Stem Cells?.

Blood ◽

10.1182/blood.v110.11.4103.4103 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4103-4103

Author(s):

Camillo Almici ◽

Rosanna Verardi ◽

Simona Braga ◽

Arabella Neva ◽

Domenico Russo ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factors ◽

Peripheral Blood ◽

Cellular Therapy ◽

Cultured Cells ◽

Basal Medium ◽

Optimal Growth ◽

Clinical Applications

Abstract Mesenchymal stem cells (MSC) are multipotent cells that are considered one of the most promising product for cellular therapy in regenerative medicine. MSC have been obtained and expanded from bone marrow and umbilical cord blood in adequate amounts for clinical applications. Under the right conditions, MSC could migrate from bone marrow into the peripheral circulation; however MSC have not been routinely isolated from peripheral blood, and studies are rare and not conclusive. The aim of the present study was to evaluate mobilised peripheral blood (MPB), obtained from patients undergoing apheresis collection of circulating hematopoietic progenitor cells, as a potential source of MSC for clinical applications. MPB samples (500–900 × 106 cells, N = 17) were separated by negative lineage-depletion immunoselection (RosetteSep). Selected cells were seeded in multi-well plates at low density in MesenCult Basal Medium without and with different combinations of growth factors (EGF, PDGF-BB, b-FGF). On reaching confluence, adherent cells were detached by 0.25% trypsin-EDTA treatment and replated for at least two passages. At each passage, surface antigen expression was analyzed by flowcytometry (CD45, CD34, CD105, CD44, CD73, CD166, CD31, HLA-DR and VE-caderine). Following immunoselection 9.5–17.1 × 106 cells were recovered from MPB samples. Cultured cells reached confluency in 3–4 weeks on first passage and in two weeks thereafter. Immunophenotyping showed negativity for CD45 antigen. The absence of growth factors in culture medium conditioned MSC growth capability, while the addition of PDGF-BB+EGF or b-FGF was able to boost the number of CD45−/CD73+/CD90+ cells in culture (see figure). However expansion remains still sub-optimal, having been reached in 8/17 samples. In conclusion, we demonstrate that MSC can be obtained from MPB, but expansion requires longer time period and appears more difficult compared to bone marrow. Therefore, further studies need to be conducted to find better culture conditions and optimal growth factor combinations to support MPB-derived MSC expansion. Figure Figure

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Immunomodulatory plasticity of mesenchymal stem cells: a potential key to successful solid organ transplantation

Journal of Translational Medicine ◽

10.1186/s12967-018-1403-0 ◽

2018 ◽

Vol 16 (1) ◽

Cited By ~ 26

Author(s):

Urvashi Kaundal ◽

Upma Bagai ◽

Aruna Rakha

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Organ Transplantation ◽

Solid Organ Transplantation ◽

Solid Organ

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Mesenchymal stem cells – a historical overview

Medical Journal of Cell Biology ◽

10.2478/acb-2020-0010 ◽

2020 ◽

Vol 8 (2) ◽

pp. 83-87

Author(s):

Katarzyna Stefańska ◽

Rut Bryl ◽

Lisa Moncrieff ◽

Nelson Pinto ◽

Jamil A. Shibli ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cellular Therapy ◽

Osteogenic Potential ◽

Experimental Medicine ◽

Cancer Tissue ◽

Multilineage Differentiation ◽

Differentiation Potential ◽

Clinical Utilization ◽

History Of

AbstractMesenchymal stem cells are currently one of the most extensively studied topics in experimental medicine, given their unique properties in terms of immunomodulation, multiple factors secretion and homing to injured tissue sites. Such characteristics were proven to be invaluable in various disease management treatments, for example in cancer, tissue regeneration or immunologic/inflammatory-related disorders. MSCs were first isolated from bone marrow in 1960-1970’s and were characterized as cells with fibroblastoid shape and osteogenic potential, which form clonogenic colonies (CFU-F – colony-forming unit-fibroblast). Nowadays the term ‘mesenchymal stem cells’ is used in regards to all of the cells meeting minimal criteria published in 2006 by the International Society for Cellular Therapy, however the name ‘mesenchymal stromal cells’ has been suggested to be more appropriate. Regardless of the name controversy, these cells exhibit multilineage differentiation potential, self-renewal ability, adhere to plastic and express specific surface antigens. In 2011 the first commercial product based on MSCs was developed and many more are expected to emerge. This review focuses on a historical perspective concerning studies on MSCs, controversies regarding their name and their characteristics and clinical utilization.Running title: The history of mesenchymal stem cells

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