Our CIRM-funded project studied a novel method of isolating and expanding diverse cell types from human pluripotent stem cells in order to increase the diversity and purity while decreasing the cost and complexity of making such products. This novel strategy utilized the method of creating expandable lines of cells from a single cell (hence the line is said to be a “clonal” cell line), where that cell was no longer pluripotent, but instead had begun to differentiate into a body cell type. These novel cell lines are called “human clonal embryonic progenitor (hEP) cell lines.” Under the grant, we extensively examined these lines to determine their potential for use in human therapeutic applications. One goal of the funded research was to determine whether their were molecules on the surface of the cells that would facilitate the repeated derivation of the lines should they prove valuable in medicine. We demonstrated that indeed, proteins could be identified that specifically recognized the lines thereby aiding in the identification of the lines. We also exposed the lines to diverse signals to explore the differentiation potential of hEP cells. In hundreds of such experiments where the cells were examined by looking at global gene expression, we discovered many novel and medically-important cell types could be made in this manner such as cartilage, bone, tendon, as well as many other cell types. In the case of the lines capable of making cartilage, we have published results showing their ability to effect the repair of damaged cartilage. An important advantage of the hEP cell lines is that they are clonally purified, therefore they represent a relatively homogenous population of cells. This is in comparison to standard ES-derived cell populations that most often comprise a widely heterogenous (mixed) population of cells. As such, we believe hEP lines have distinctive advantages, both in terms of safety (better defined biology without unintended admixture of diverse cell types) and in terms of manufacturing (better ability to provide well defined assays and measurements during the derivation and cell production process).