Year 2
Our plan is to find ways to facilitate transplants of stem cell-derived cells to genetically different recipients. We propose to inactivate the rejection capability of natural killer cells, a white blood cell type that can reject transplanted cells. To explore this we started with a mouse model. Previously we generated evidence that there are one or more cell types in normal mice can inactivate the rejection capacity of natural killer cells. Our first aim is to identify that cell type to see it can be injected into mice to inactivate the natural killer cells. In the last year we discovered that the relevant cells include both blood cell types and non blood cell types. We showed however, that tolerance induced by non-blood cell types induces a more stable type of tolerance than that induced by blood cell types. We went on to develop a system in live mice to test subtypes of cells that can induce tolerance. Using this system, we could show that a heterogeneous mixture of blood cell types could induce tolerance. The system is suitable for testing specific blood cell, or non blood cell, types for their capacity to induce tolerance. We will undertake those studies in the coming months. The hope is that once the cell type has been identified, it could be generated from stem cells and injected into patients to facilitate transplants of other cell types derived from the same stem cells.