Abstract
Rheumatoid arthritis (RA) is a chronic immune-mediated disease managed by conventional synthetic drugs, such as methotrexate (MTX), and targeted drugs including biological agents. Cell-based therapeutic approaches are currently developed in RA, mainly mesenchymal stroma cell-based approaches. Early-stage apoptotic cells possess direct and indirect anti-inflammatory properties. During the elimination of dying cells (a process called efferocytosis), specific mechanisms operate to control immune responses. There are compelling evidences in experimental models of arthritis indicating that apoptotic cell administration may benefit joint inflammation, and may even have therapeutic effects on arthritis. Additionally, it has been demonstrated that apoptotic cells could be administered with standard treatments of RA, such as MTX or TNF inhibitors (TNFi), given even a synergistic response with TNFi. Interestingly, apoptotic cell infusion has been successfully experienced to prevent acute graft-vs.-host disease after hematopoietic cell transplantation in patients with hematologic malignancies, with a good safety profile. In this mini-review, the apoptotic cell-based therapy development in arthritis is discussed, as well as its transfer in the short-term to an innovative treatment for patients with RA. The use of apoptotic cell-derived factors, including secretome or phosphatidylserine-containing liposomes, in RA are also discussed.
Highlights
Rheumatoid arthritis (RA) is a chronic immune-mediated disease that primarily affects the peripheral joints
A preventive effect of apoptotic cell administration on clinical scores has been observed in all the arthritis models tested [47,48,49,50], except in the serum transfer-induced arthritis (STIA) model [47]
Implication of IL-10-producing T cells [T regulatory 1 (Tr1) cells], Treg and/or IL-10-secreting Breg cells has been shown to be triggered by apoptotic cell infusion in arthritis models and associated with the reduction of joint inflammation [47,48,49] (Table 1)
Summary
Rheumatoid arthritis (RA) is a chronic immune-mediated disease that primarily affects the peripheral joints. In this review, we will comment the current knowledge of apoptotic cell-based treatment in arthritis, and discuss the potential use of this cellular therapy in patients with RA. Apoptotic cell-based therapies have been evaluated through intravenous (IV), intraperitoneal (IP), or IA administration of early stage apoptotic cells in the main arthritis models.
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