The intra-hepatic population of liver progenitor cells expands during liver injury when hepatocyte proliferation is inhibited. These cells can be purified by density gradient centrifugation and cultured. Separated by size only this Population contains small cells of hematopoietic, epithelial and endothelial lineages and is thought to contain liver stem cells. The identity of liver stem cells remains unknown although there is some evidence that tissue Sca1(+) CD45(-) cells display progenitor cell characteristics. We identified both intra-hepatic and gall bladder Sca1(+) cells following liver injury and expanded ex vivo Sca1 cells as part of heterogenous Cell culture or as a Purified population. We found significant difference between the proliferation of Sca-1 cells when plated on laminin or Collagen I while proliferation of heterogenous Population was not affected by the extracellular matrix indicating the necessity for Culture of Sca1(+) cells with laminin matrix or laminin producing cells in long term liver progenitor cell cultures. (C) 2009 Elsevier Inc. All rights reserved.