Pooled MSCs for treatment of severe hemorrhage.

摘要

MSCs have attracted great interest in regenerative medicine because they can differentiate into several tissues of mesenchymal origin, such as bone, cartilage, tendon and cardiomyocytes. Infused MSCs improve the outcome of acute renal, neural and lung injury, possibly by promoting a shift from production of proinfiammatory cytokines to antiinflammatory cytokines at the site of injury. MSCs also have immunomodulatory effects and they reduce alloreactive T-cell responses and mitogenic responses in vitro. We investigated the use of MSCs for immuno-modulation in patients with acute GVHD of the gastrointestinal tract, liver and skin, and were able to demonstrate MSC donor DNA in the target organ. Subsequently, MSCs were also used for tissue toxicity such as hemorrhagic cystitis, pneumomediastinum and perforated colon. Responses were seen in half of the patients, although many subsequently died from infection. MSCs reduced alloreactivity in MLCs in vitro equally effectively, irrespective of whether they were autologous or HLA mismatched. This has also been confirmed in vivo, in which responses in GVHD were the same regardless of whether the MSCs were HLA identical, HLA haploidentical or HLA mismatched.