Mesenchymal stem cells suppress B-cell terminal differentiation

Asari, Sadaki; Itakura, Susumu; Ferreri, Kevin; Liu, Chih-Pin; Kuroda, Yoshikazu; Kandeel, Fouad; Mullen, Yoko

doi:10.1016/j.exphem.2009.01.005

Cited by 303 publications

(258 citation statements)

References 45 publications

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“…This interpretation is consistent with the finding that MSC therapy does not interfere with virus-specific T cell responses [Karlsson et al, 2008]. Studies of the influence of MSC on B cell function have also generated heterogeneous results [Corcione et al, 2006;Rasmusson et al, 2007;Rafei et al, 2008;Traggiai et al, 2008;Asari et al, 2009]. Co-culture of human MSC with purified B cell populations under stimulatory conditions may inhibit B cell activation (proliferation differentiation, immunoglobulin (Ig) production and chemotaxis) [Corcione et al, 2006].…”

Section: Msc Suppression Of Adaptive Immunitysupporting

confidence: 74%

Allogeneic mesenchymal stem cells: Agents of immune modulation

2011

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Adult mesenchymal stem cells possess a remarkably diverse array of immunosuppressive characteristics. The capacity to suppress the regular processes of allogeneic rejection, have allowed the use of tissue mismatched cells as therapeutic approaches in regenerative medicine and as agents of immune deviation. This review describes recent advances in understanding the mechanistic basis of mesenchymal stromal or stem cells (MSC) interaction with innate immunity. Particular emphasis is placed on the effect of Toll-like receptor signalling on MSC and a hypothesis that innate immune signals induce a 'licensing switch' in MSC is put forward. The mechanisms underlying MSC suppression of T cell responses and induction of regulatory populations are surveyed. Conflicting data regarding the influence of MSC on B cell function are outlined and discussed. Finally the limits to MSC mediated immune modulation are discussed with reference to the future clinical application of novel cell therapies. J. Cell. Biochem. 112: 1963-1968, 2011. ß 2011 KEY WORDS: MESENCHYMAL STEM CELLS; IMMUNOLOGY; CELL THERAPY C ell-based therapies to treat human disease are set to become clinical reality. To the fore of these novel approaches is the use of adult mesenchymal stromal or stem cells (MSC). The term 'mesenchymal stem cell' was coined by Caplan in 1991 [Caplan, 1991] to describe the rare population of bone marrow derived, plastic adherent cells discovered by Friedenstein and Petrokova [1966]. Originally these stromal cells were assumed to directly repair degenerative disease by differentiation; however, it is now appreciated that MSC also release soluble factors that act in a paracrine manner to promote repair [Caplan, 2009]. However, while MSC might be considered as trophic agents that guide the processes of tissue repair, the nature of the trophic activities remain ill defined.The beneficial actions of MSC encompass anti-apoptotic, cytoprotective effects and the promotion of angiogenesis [Caplan, 2009] and it is the multifactorial, coordinated and targeted features of MSC that make the cell therapy approach superior to small molecule modalities. Angiogenic action is likely to be an important component of tissue repair; pericyte mediated vascular stability contributes to wound healing and tissue resident MSC may be derived from a perivascular precursor [Bianco et al., 2010], and may be intimately involved in neovascularisation of wounds and therefore regeneration.Whilst the above features are important attributes of MSC biology, one trophic function has become the subject of intense scrutiny in the last 7 years. It is now apparent that MSC are powerful modulators of the mammalian immune response. These findings date back to studies which demonstrated that tissue mismatched (allogeneic) and even species mismatched (xenogeneic) MSC were effective cell therapies [Bartholomew et al., 2002;Grinnemo et al., 2004]. The implications were that MSC would disobey the regular rules of tissue transplantation and enjoy a degree of immune privilege,...

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Section: Msc Suppression Of Adaptive Immunitysupporting

confidence: 74%

Allogeneic mesenchymal stem cells: Agents of immune modulation

2011

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“…In the present study, UC MSCs significantly depressed the serum concentration of IL-4 3 months after transplantation, which may have inhibited humoral immunity in the SLE patients and indirectly suppressed the secretion of autoantibodies, especially anti-dsDNA antibody (which is most closely correlated with clinical outcome in mice and humans with SLE [39]). In addition, it has been shown that MSCs exert a suppressive effect on B cell activation and terminal differentiation to plasma cells (40); therefore, suppression of humoral immunity may be one mechanism involved in the treatment effect of UC MSCT.…”

Section: Discussionmentioning

confidence: 99%

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

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

424

310

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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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“…IL-6, which is involved in the reversion of the maturation of dendritic cells to an immature phenotype, mediates MSC interference with the maturation of dendritic cells [50]. MSCs were found to inhibit B-cell proliferation by releasing soluble factors, especially B lymphocyte-induced maturation protein-1(Blimp-1), which is necessary for immunoglobulin production [72].…”

Section: Mscs and Target Cells: A Long-distance Relationshipmentioning

confidence: 99%

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

Pierro

Thébaud

2016

Curr Stem Cell Rep

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The imbalance of inflammatory and antiinflammatory responses in favor of inflammation plays a major role in the pathogenesis of many neonatal diseases. Inflammation in the perinatal period carries important longterm consequences, including neurodevelopmental and respiratory complications. Treatments able to restore immune homeostasis may reduce neonatal mortality and prevent longterm deleterious multi-organ consequences of unchecked inflammation. Mesenchymal stromal cells are a heterogenous group of progenitors cells with potent anti-inflammatory and immunomodulatory potential, among other diverse mechanisms of action. Thus, mesenchymal stromal cells (MSCs) may represent a novel and effective therapy for several neonatal diseases, potentially capable of preventing their longterm complications. This paper reviews the role of inflammation in the perinatal period and the therapeutic role of MSCs, focusing on their anti-inflammatory potential.

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Mesenchymal stem cells suppress B-cell terminal differentiation

Cited by 303 publications

References 45 publications

Allogeneic mesenchymal stem cells: Agents of immune modulation

Allogeneic mesenchymal stem cells: Agents of immune modulation

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

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

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