The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell. microenviromnent, and etiology of the liver injury. The following experiments investigated the impact of TGF-beta1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endoeenously produced TGF-beta1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF- l supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-beta1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease. (C) 2005 Elsevier Inc. All rialits reserved.