Concise Review: Apoptotic Cell-Based Therapies–Rationale, Preclinical Results and Future Clinical Developments

Saas, Philippe; Daguindau, Étienne; Perruche, Sylvain

doi:10.1002/stem.2361

Cited by 50 publications

(60 citation statements)

References 81 publications

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“…Several studies have demonstrated the induction of immune tolerance in different settings in response to DC phagocytosis of apoptotic cells (reviewed in (63, 64)). The therapeutic potential of apoptotic cell induced immunosuppression has been explored based on data in animal models demonstrating effective control of chronic inflammation in the settings of allograft rejection and graft- versus -host disease (65, 66), diabetes (67), arthritis (68–71), septic shock (72), and other chronic and acute inflammatory conditions (reviewed in (73)). A recently completed phase I/IIa clinical trial concluded that a single infusion of early apoptotic donor cells to 13 patients with hematological malignancies a day prior to hematopoietic stem cell transplantation, is a safe and potentially effective prophylactic therapy for acute graft- versus -host disease (74).…”

Section: Suppression Of Inflammation and Immune Response By Apoptoticmentioning

confidence: 99%

The many ways tissue phagocytes respond to dying cells

Blander

2017

Immunological Reviews

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Summary Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells that have undergone apoptosis in situ has revealed a division of labor among the tissue resident phagocytes that sample them. Macrophages are uniquely programmed to process internalized apoptotic cell-derived fatty acids, cholesterol and nucleotides, as a reflection of their dominant role in clearing the bulk of apoptotic cells. Dendritic cells carry apoptotic cells to lymph nodes where they signal the emergence and expansion of highly suppressive regulatory CD4 T cells. A broad suppression of inflammation is executed through distinct phagocyte-specific mechanisms. A clever induction of negative regulatory nodes is notable in dendritic cells serving to simultaneously shut down multiple pathways of inflammation. Several of the genes and pathways modulated in phagocytes in response to apoptotic cells have been linked to chronic inflammatory and autoimmune diseases such as atherosclerosis, inflammatory bowel disease and systemic lupus erythematosus. Our collective understanding of old and new phagocyte functions after apoptotic cell phagocytosis demonstrates the enormity of ways to mediate immune suppression and enforce tissue homeostasis.

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Section: Suppression Of Inflammation and Immune Response By Apoptoticmentioning

confidence: 99%

The many ways tissue phagocytes respond to dying cells

Blander

2017

Immunological Reviews

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“…Apoptotic cells exert immunomodulatory effects either by releasing active immune mediators directly or indirectly via the modulation of phagocytes and dendritic cells [52]. The infusion of apoptotic cells attenuates systemic concentrations of inflammatory cytokines [53,54] Pigs receiving apoptotic cell secretome had an ejection fraction (57.0 versus 40.5 %), improved cardiac output (4.0 versus 2.4 L/min), and reduced infarct area (12.6 versus 6.9 %) compared to controls (see Table 2).…”

Section: Apoptosis and The Rise Of The Phoenix Signaling Pathwaymentioning

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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“…Apoptotic cells exert immunomodulatory effects either by releasing active immune mediators directly or indirectly via the modulation of phagocytes and dendritic cells [52]. The infusion of apoptotic cells attenuates systemic concentrations of inflammatory cytokines [53, 54], whereas anti-inflammatory cytokines, such as IL-10 [55–57] and/or TGF-β [53, 57], are released.…”

Section: Apoptosis and The Rise Of The Phoenix Signaling Pathwaymentioning

confidence: 99%

“…Based on the immunomodulatory capacities of apoptotic cells during the last decade, several pre-clinical studies evaluated their usage for the treatment of autoimmune disease or organ transplantation (Table 1) (reviewed in [52]).…”

Section: Pre-clinical Application Of Nucleated Apoptotic Cellsmentioning

confidence: 99%

“…This table is adapted from [52] Ag antigen, ATG anti-thymocyte globulin, BALF broncho-alveolar lavage fluid, BSA bovine serum albumin, CIA collagen-induced arthritis, DC dendritic cells, DSS dextran sulfate sodium, EAE experimental autoimmune encephalomyelitis, GvHD graft-versus-host disease, i.v . intravenous, i.p .…”

Section: Pre-clinical Application Of Nucleated Apoptotic Cellsmentioning

confidence: 99%

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Peripheral blood mononuclear cell secretome for tissue repair

et al. 2016

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For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings. However, a growing body of evidence indicates that other cell types, such as peripheral blood mononuclear cells (PBMCs), are capable of releasing significant amounts of biologically active paracrine factors that exert beneficial regenerative effects. The apoptotic PBMC secretome has been successfully used pre-clinically for the treatment of acute myocardial infarction, chronic heart failure, spinal cord injury, 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: Apoptotic Cell-Based Therapies–Rationale, Preclinical Results and Future Clinical Developments

Cited by 50 publications

References 81 publications

The many ways tissue phagocytes respond to dying cells

The many ways tissue phagocytes respond to dying cells

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

Peripheral blood mononuclear cell secretome for tissue repair

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