The role and regulation of complement activation as part of the thromboinflammation elicited in cell therapies

- During cell therapies cells come in contact with blood and trigger thromboinflammatory reactions.
- Indications for cell therapy include diabetes mellitus, liver insufficiency, and GVHD.
- Recently, progress has been made, but tissue loss due to thromboinflammation is a major problem.
- Mechanisms for thromboinflammation with special focus on complement activation are described.
- We discuss strategies to control thromboinflammation by novel coatings or systemic inhibitors.

Cell therapies in which the cells come into direct contact with blood and other body fluids are emerging treatment procedures for patients with various diseases, such as diabetes mellitus, liver insufficiency, and graft-versus-host disease. However, despite recent progress, these procedures are associated with tissue loss caused by thromboinflammatory reactions. These deleterious reactions involve the activation of the complement and coagulation cascades and platelet and leukocyte activation, ultimately resulting in clot formation and damage to the implanted cells.In this concept review, we discuss the basic mechanisms underlying the thrombininflammatory process, with special reference to the engagement of complement and emerging strategies for the therapeutic regulation of these reactions that include the use of selective systemic inhibitors and various procedures to coat the surfaces of the cells. The coating procedures may also be applied to other treatment modalities in which similar mechanisms are involved, including whole organ transplantation, treatment with biomaterials in contact with blood, and extracorporeal procedures.