Acute Myeloid Leukemia (AML) is a cancer that is related to the blood and bone marrow. In a normal human, the bone marrow produces stem cells that eventually differentiate into either myeloid stem cells or a lymphoid stem cell. Lymphoid stem cells become immune cells, and myeloid stem cells can become either red blood cells (RBC), white blood cells (WBC), or platelets. In AML, the myeloid stem cells do not differentiate correctly and begin to produce abnormal RBC's, WBC's, and platelets - this is called leukemia. When leukemia cells begin to build in the blood and bone marrow, there is less room in the body for healthy cells, putting the patient at risk for infection, ischemia, and heavy bleeding.
Current treatment of this disease includes chemotherapy and stem cell therapy to replace previously destroyed myeloid cells, but, there remain many complications associated with this treatment, including host-versus-graft disease, which entails the transplanted cells regarding the recipient's body as foreign. Once this happens, the transplanted cells attack the recipient's body which can complicate the life of the patient heavily. Recently, though, studies have shown that induced pluripotent stem cells can be used to bypass bone marrow stem cell collection, as well as host-versus-graft disease. Upon exposure to the correct cytokines and growth factors, these stem cells are able to differentiate into hematopoietic stem cells. The aim of our research is to optimize Induced Pluripotent Stem Cell (iPSC) to Hematopoietic Stem Cell (HSC) differentiation by investigating the effects of OP9 cells in differentiation. While this is an effective method of generating HSCs, our aim is to determine whether the OP9 cells are necessary to induce differentiation, or if simply the proteins secreted by OP9 cells are sufficient. Furthermore, we look to isolate and identify the proteins that are responsible for the differentiation of the secreted proteins are found to be the cause for differentiation. The focus of the experiment is on the OP9 co-culturing methodology and the isolation of molecular components that are responsible for induced hematopoiesis. The results of this research will be critical in further understanding hematopoiesis and the engraftment potential of iPSCs in patients of leukemia.