Inhibition of Humoral Response to Allogeneic Porcine Mesenchymal Stem Cell With 12 Days of Tacrolimus

Poncelet, Alain; Nizet, Yannick; Vercruysse, Jonathan; Hiel, Anne Lise; Saliez, Alain; Gianello, Pierre

doi:10.1097/tp.0b013e31818bd96f

Cited by 21 publications

(18 citation statements)

References 57 publications

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“…The antibody surge in our study occurred rapidly (within 5 days) and accompanied the strong cellular immune activation. Reports that short-term T-cell-specific immunosuppression prevented the antibody response against transplanted MSCs support the hypothesis of a T-cell-driven humoral response against cellular grafts (Poncelet et al, 2008). Ongoing humoral rejection of islet grafts was successfully treated with an anti-CD20 monoclonal antibody (Kessler et al, 2009).…”

Section: Discussionmentioning

confidence: 71%

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

Deuse

Seifert

Phillips

et al. 2011

Journal of Cell Science

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KD was followed by flow cytometry and showed levels between 1% and 12% of those of naïve hESC between days 7 and 42 (means ± s.e.m.). (b) A total of 10 6 hESCs or hESC KD were transplanted into the gastrocnemius muscle of either immunocompetent Balb/c or severely immunocompromised SCID-beige mice. All ten Balb/c mice rapidly rejected the hESC transplants, whereas the cells survived in ten SCID-beige recipients. Rejection of hESC KD was markedly attenuated and four out of ten hESC KD grafts achieved long-term survival. 4128 Author Correction The first author apologises for these errors.Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells SummaryHuman embryonic stem cells (hESCs) can serve as a universal cell source for emerging cell or tissue replacement strategies, but immune rejection of hESC derivatives remains an unsolved problem. Here, we sought to describe the mechanisms of rejection for naïve hESCs and upon HLA class I (HLA I) knockdown (hESC KD ). hESCs were HLA I-positive but negative for HLA II and co-stimulatory molecules. Transplantation of naïve hESC into immunocompetent Balb/c mice induced substantial T helper cell 1 and 2 (Th1 and Th2) responses with rapid cell death, but hESCs survived in immunodeficient SCID-beige recipients. Histology revealed mainly macrophages and T cells, but only scattered natural killer (NK) cells. A surge of hESC-specific antibodies against hESC class I, but not class II antigens, was observed. Using HLA I RNA interference and intrabody technology, HLA I surface expression of hESC KD was 88%-99% reduced. T cell activation after hESC KD transplantation into Balb/c was significantly diminished, antibody production was substantially alleviated, the levels of graft-infiltrating immune cells were reduced and the survival of hESC KD was prolonged. Because of their very low expression of stimulatory NK ligands, NK-susceptibility of naïve hESCs and hESC KD was negligible. Thus, HLA I recognition by T cells seems to be the primary mechanism of hESC recognition, and T cells, macrophages and hESC-specific antibodies participate in hESC killing.

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Section: Discussionmentioning

confidence: 71%

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

Deuse

Seifert

Phillips

et al. 2011

Journal of Cell Science

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“…Second, it is of interest to know whether immunosuppressive therapies currently prescribed in organ transplantation can be effectively used to prevent anti-donor immune responses to alloMSCs in vivo without diminishing therapeutic efficacy. In this regard, Poncelet et al (2008) have shown, in a miniature pig model of myocardial infarction, that the calcineurin inhibitor tacrolimus significantly attenuated the anti-donor antibody response to allo-MSCs delivered directly into the infarct. Recently, Ge et al (2009) also demonstrated that a combination of allo-MSC infusion and low-dose sirolimus (rapamycin) therapy resulted in long-term survival of fully MHC-mismatched heart transplants in mice.…”

Section: To What Extent Are Allo-mscs Immunoprivilegedmentioning

confidence: 99%

Immunological Aspects of Allogeneic Mesenchymal Stem Cell Therapies

2010

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Allogeneic mesenchymal stem or stromal cells (MSCs) are proposed as cell therapies for degenerative, inflammatory, and autoimmune diseases. The feasibility of allogeneic MSC therapies rests heavily on the concept that these cells avoid or actively suppress the immunological responses that cause rejection of most allogeneic cells and tissues. In this article the validity of the immune privileged status of allogeneic MSCs is explored in the context of recent literature. Current data that provide the mechanistic basis for immune modulation by MSCs are reviewed with particular attention to how MSCs modify the triggering and effector functions of innate and adaptive immunity. The ability of MSCs to induce regulatory dendritic and T-cell populations is discussed with regard to cell therapy for autoimmune disease. Finally, we examine the evidence for and against the immune privileged status of allogeneic MSCs in vivo. Allogeneic MSCs emerge as cells that are responsive to local signals and exert wide-ranging, predominantly suppressive, effects on innate and adaptive immunity. Nonetheless, these cells also retain a degree of immunogenicity in some circumstances that may limit MSC longevity and attenuate their beneficial effects. Ultimately successful allogeneic cell therapies will rely on an improved understanding of the parameters of MSC-immune system interactions in vivo.

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“…Based on our previous work on tolerance after allogeneic full organ transplantation [13] as well as on our most recent experimental work demonstrating that with a moderate transient immunosuppression, the primary immune response to allogeneic MSC transplantation could be overcome [14], we decided to use in the present study a 12-day course of tacrolimus.…”

Section: Introductionmentioning

confidence: 99%

Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model☆

Poncelet

Hiel

Vercruysse

et al. 2010

European Journal of Cardio-Thoracic Surgery

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Inhibition of Humoral Response to Allogeneic Porcine Mesenchymal Stem Cell With 12 Days of Tacrolimus

Cited by 21 publications

References 57 publications

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

Immunological Aspects of Allogeneic Mesenchymal Stem Cell Therapies

Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model☆

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