Abstract 4580

Infusion of third-party mesenchymal stem cells (MSCs) appears to be a promising therapy for steroid-refractory acute graft-versus-host disease (GvHD). Little is known about how MSCs interact with the innate immune system after clinical infusion. In this study, we show that exposure of MSCs to ABO-compatible human blood activates the complement system, which triggers complement-mediated effector cell functions, and correlates with the immunosuppressive properties of MSCs. We found deposition of the complement component 3 (C3) derived opsonins iC3b and C3dg on MSCs, and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. These events triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation; but could be prevented by culturing MSCs in human ABserum or by blocking complement function. Our study demonstrates the important role of the complement system as a possible mediator of immune modulation in clinical applications using MSCs, and implies that complement activation may substantially affect the treatment efficiency.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
anaphylatoxins, cd18 antigens, complement 3, complement activation, complement system proteins, graft-versus-host disease, graft-versus-host disease, acute, immunosuppressive agents, inactivated c3b, infusion procedures

Author notes

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Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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