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

Jiang, Xiao Xia; Zhang, Yi; Liu, Bing; Zhang, Shuang Xi; Wang, Ying; Yu, Xiao Dan; Mao, Ning

doi:10.1182/blood-2004-02-0586

Cited by 1,182 publications

(941 citation statements)

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“…Indeed, MSC have been shown to inhibit the maturation of monocyte-derived myeloid DC by downregulating both the surface expression of CD11c, CD83, MHC class II and costimulatory molecules, and the production of IL-12 upon TLR-mediated DC activation [47,[62][63][64]. Following interaction with MSC, myeloid DC have been shown to produce a decreased amount of TNF-a while plasmacytoid DC switched to an increased production of IL-10 [46].…”

Section: Msc and Dendritic Cellsmentioning

confidence: 99%

“…This effect, in turn, led to decreased IFN-c production by Th1 cells, increased IL-4 secretion by Th2 cells, and an increased number of regulatory T cells [46,47]. The mechanism of MSCinduced inhibition of DC differentiation and function appears to be mediated by soluble factors, such as PGE-2, released upon cell-to-cell contact [46,63].…”

Section: Msc and Dendritic Cellsmentioning

confidence: 99%

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Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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Section: Msc and Dendritic Cellsmentioning

confidence: 99%

Section: Msc and Dendritic Cellsmentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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“…The neurotrophic properties of these cells were demonstrated in several models of neurological diseases, including stroke [183] and trauma [184]. BMSC possess wide immunomodulatory functions; they inhibit maturation of monocytes into dendritic cells [185], they impair the antigen-presenting function of dendritic cells [186,187], they inhibit T-cell proliferation in a non-major histocompatibility complex (MHC) restricted manner [188][189][190], they induce a shift of T cells to an antiinflammatory (IL-4 producing) phenotype [190], and they inhibit B-cell proliferation and differentiation [191]. Several soluble factors have been implicated in the immunomodulatory functions of BMSC, such as indoleamine 2,3-dioxygenase, transforming growth factor-β1, hepatocyte growth factor, IL-10, and others, but these effects were also partially dependent on cell-cell contact (for more details see Uccelli et al [192]).…”

Section: Therapeutic Plasticity Of Non-neural Stem Cellsmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

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“…Recent studies have indicated that these pluripotent cells also differentiate into endoderm and neuroectoderm lineages, including neurons, hepatocytes, and cardiocytes (8)(9)(10)). An important function of MSCs for autoimmune diseases is their immunomodulatory effect on various activated lymphoid cells, such as T cells, B cells, natural killer cells, and dendritic cells (11)(12)(13). MSCs express low levels of HLA class I major histocompatibility complex (MHC) molecules and are negative for class II MHC costimulatory molecules such as CD80, CD86, and CD40 (14).…”

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confidence: 99%

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

412

304

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Objective. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE).Methods. We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines.Results. From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3-28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1-and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.Conclusion. Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE.Systemic lupus erythematosus (SLE) is an inflammatory disease with protean manifestations, ranging from relatively minor skin and joint symptoms to severe life-threatening major organ involvement, such as nephritis and neuropsychiatric complications (1). It is characterized by the presence of autoreactive T and B lymphocytes, with polyclonal activation of B cells and the consequent production of autoantibodies by plasma ClinicalTrials.gov identifier: NCT00698191.

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

Cited by 1,182 publications

References 42 publications

Immunoregulatory function of mesenchymal stem cells

Immunoregulatory function of mesenchymal stem cells

Cell Therapy for Multiple Sclerosis

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

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