Concerns arising from MSC retrieval from cryostorage and effect on immune suppressive function and pharmaceutical usage in clinical trials

Abstract

Marrow‐derived mesenchymal stromal cells ( MSC s) from either autologous or from random donor origin are being investigated in a large number of clinical trials as a cellular pharmaceutical for treatment of immune disorders such as Crohn's disease, systemic lupus erythematous, multiple sclerosis, Gv HD and others. Most typically, a polyclonal pool of ex vivo culture expanded cells is cryopreserved after serial passaging and banked for later use. Human subjects subsequently receive an intravenous transfusion of MSC s which were retrieved from cryostorage no more than a few hours beforehand. It is assumed that viable, immediate post‐thaw MSC s deploy the same biochemical, homing and immune modulatory features as their pre‐freeze counterparts. We here propose that this assumption may be erroneous and may provide, in part, an explanation for discrepancy between pre‐clinical models of MSC effectiveness and negative outcome of a large prospective randomized Phase III clinical trial (NCT00366145) of random donor MSC s for treatment of steroid‐resistant acute Gv HD .