Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation

The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression. When examining patients with GvHD who received…

• KC
  King's College London
• B
  Bloodwise

  Awards: 14019, award297906, award297905, award297904, 12006, 15029
• MR
  Medical Research Council

  Awards: MR/L022699/1, MC_PC_14105, MR/J006742/1, MC_G0802523