Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells

Mougel, F.; Bonnefoy, Francis; Kury-Paulin, S; Borot, Sophie; Perruche, Sylvain; Kantélip, B.; Penfornis, A.; Saas, Philippe; Kleinclauss, F.

doi:10.1016/j.diabet.2012.08.008

Cited by 12 publications

(23 citation statements)

References 28 publications

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“…Most of the studies report the prevention of the disease, which means that apoptotic cells were infused during the triggering stage of the disease (i.e., at immunization with autoantigens or at the time of transplantation) or before the disease occurred. This is true for Type 1 diabetes in nonobese diabetic mice [47], experimental autoimmune encephalomyelitis [12,62,106], arthritis [36,107,108], fulminant hepatitis [109], contact hypersensitivity [110][111][112], acute and chronic graft rejection [86,[113][114][115], hematopoietic cell engraftment [2,14,85,116,117], acute GvHD disease [14] and reduction of infarction size after acute myocardial infarction [118,119]. Thus, it is difficult to transpose this in the clinical setting where, in general, the disease is already present when a therapeutic solution has to be found.…”

Section: Preclinical Data Using Early Apoptotic Cell Infusion In Expementioning

confidence: 93%

“…The infused apoptotic cell number and the schedule of infusion are relatively homogeneous among the different studies: 5 × 10 5 -10 7 in mice [2,12,14,36,48,63,85,86,92,106,107,[109][110][111][112][113][114][115][116][117]121,122], or 8 × 10 6 -10 8 in rats [108,118,119]. In general, only one infusion was performed (18 out of 21).…”

Section: Hematopoietic Engraftmentmentioning

confidence: 99%

“…; 35 Gy g-irradiated apoptotic spleen cells (5 × 10 6 ); donor-specific; and possible involvement of Tregs [113] Hematopoietic cell Tx…”

Section: Cardiac Allograftmentioning

confidence: 99%

“…Cells rendered apoptotic are mainly leukocytes at an early apoptotic stage (including mouse spleen cells in 13 [2,14,85,86,106,[110][111][112][113][114][115][116][117], rat peripheral blood mononuclear cells (PBMCs) in two [118,119], mouse T cells in two [12,63], the human Jurkat T-cell line in one [92] and rat or mouse thymocytes in three studies [36,107,108], while mouse neutrophils [121] and a mouse b-cell line were used in one study [48]); The tolerogeneic apoptotic stimuli used are as follows: g-irradiation in ten [2,14,85,108,113,[116][117][118][119]122], UVB irradiation in seven [48,86,92,109,110,114,115], Fas-mediated death in three [2,12,63], spontaneous apoptosis in culture due to survival factor deprivation in two [107,121] and dexamethasone treatment in one study [36].…”

Section: Hematopoietic Engraftmentmentioning

confidence: 99%

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Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

2013

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Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

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Section: Preclinical Data Using Early Apoptotic Cell Infusion In Expementioning

confidence: 93%

Section: Hematopoietic Engraftmentmentioning

confidence: 99%

“…; 35 Gy g-irradiated apoptotic spleen cells (5 × 10 6 ); donor-specific; and possible involvement of Tregs [113] Hematopoietic cell Tx…”

Section: Cardiac Allograftmentioning

confidence: 99%

Section: Hematopoietic Engraftmentmentioning

confidence: 99%

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Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

2013

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“…In addition, gamma-irradiated splenocytes promote allogeneic bone marrow engraftment [83,84,92]. The infusion of apoptotic leukocytes 7 days before the administration of allogeneic pancreatic islets has been shown to improve transplant survival through the modulation of regulatory T-cells [81].…”

Section: Pre-clinical Application Of Nucleated Apoptotic Cellsmentioning

confidence: 99%

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

Beer¹,

Mildner²,

Gyöngyösi³

et al. 2018

Cell Engineering and Regeneration

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stroke, and wound healing. In this review we describe the benefits of choosing PBMCs instead of stem cells in regenerative medicine and characterize the factors released from apoptotic PBMCs. We also discuss pre-clinical studies with apoptotic cell-based therapies and regulatory issues that have to be considered when conducting clinical trials using cell secretome-based products. This should allow the reader to envision PBMC secretome-based therapies as alternatives to all other forms of cell-based therapies.

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Concise Review: Mechanisms Behind Apoptotic Cell-Based Therapies Against Transplant Rejection and Graft versus Host Disease

Morelli

Larregina

2016

Stem Cells

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The main limitations to the success of transplantation are the anti-graft response developed by the recipient immune system, and the adverse side effects of chronic immunosuppression. Graft-versus-host disease (GVHD) triggered by donor-derived T lymphocytes against the recipient tissues is another serious obstacle in the field of hematopoietic stem cell transplantation. Several laboratories have tested the possibility of promoting antigen (Ag)-specific tolerance for therapy of graft rejection, GVHD, and autoimmune disorders, by developing methodologies that mimic the mechanisms by which the immune system maintains peripheral tolerance in the steady state. It has been long recognized that the silent clearance of cells undergoing apoptosis exerts potent immune-regulatory effects and provides apoptotic cell-derived Ags to those Ag-presenting cells (APCs) that internalize them, in particular macrophages and dendritic cells. Therefore, in situ-targeting of recipient APCs by systemic administration of leukocytes in early apoptosis and bearing donor Ags represents a relatively simple approach to control the anti-donor response against allografts. Here, we review the mechanisms by which apoptotic cells are silently cleared by phagocytes, and how such phenomenon leads to down-regulation of the innate and adaptive immunity. We discuss the evolution of apoptotic cell-based therapies from murine models of organ/tissue transplantation and GVHD, to clinical trials. We make emphasis on potential limitations and areas of concern of apoptotic cell-based therapies, and on how other immune-suppressive therapies used in the clinics or tested experimentally likely also function through the silent clearance of apoptotic cells by the immune system.

show abstract

Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells

Cited by 12 publications

References 28 publications

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

Concise Review: Mechanisms Behind Apoptotic Cell-Based Therapies Against Transplant Rejection and Graft versus Host Disease

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