? ? Mesenchymal stem cells (MSCs) are one of the most extensively studied adult stem cells and have broad potential uses. A few of their uses include, studying developmental pathways, disease modeling, in vitro toxicology models, compound screening, humanized animal models and potentially cellular therapy. Although MSC are proliferative, a drawback with these cells is that unlike human embryonic stem cell (ESC), MSC are not immortal stem cells. For any application that uses large quantities of MSC, such as high throughput drug compound screening, eventually MSC will have to be re-derived, likely from a different genetic background, thus assay responses may differ among genetic backgrounds and could reduce assay consistency and robustness. If reporter genes are added or line specific characteristics are found, these unique characteristics may be lost when MSC are freshly isolated from different genotypes. Aruna Biomedical proposes to develop turnkey kits containing human ESC derived monolayer cultures of MSC that can be reliably and quantitatively differentiated into MSC derived lineages. This project follows the model set forth in a previous NIH STTR to Aruna for neural stem cells. That grant resulted in the first human ESC derived product commercially available to the research community. These Aruna kits and services are for neural stem cell researchers and we currently provide custom assays for drug discovery to major pharmaceutical companies. We have preliminary data to suggest that this same monolayer differentiation and culture platform technology will generate uniform MSC under the right conditions. For this project, we propose to 1) repeatedly derive adherent cultures of MSC populations from human ESCs (WA09), and then 2) demonstrate reproducible MSC lineage differentiation of hESC derived MSC cells, leading to a phase II application that will produce an optimized process. In turn these will provide never before available MSC kits to the research community in multiple formats 1) a kit containing the cells and reagents needed to propagate and differentiate the ESC derived MSC into multiple lineages 2) a reagent kit to researchers who wish to derive their own human MSC lines from ESC. This will allow researchers to add specific markers, make genetic changes to a master ESC line prior to the derivation of the MSC and then re-derive MSC from the master ESC line again at a later date 3) customized genetically modified MSC to meet the needs of the researchers.
Mesenchymal stem cells are useful in cell therapy and stem cell research but they have a limited lifespan in culture. We will develop a unique and limitless supply of mesenchymal stem cells derived from human embryonic stem cells, opening up new uses and enhance existing uses of these important cell types. ? ? ?
