Stem Cell Conversion Heralds New Treatment for Blood Disorders
Scientists from the University of Wisconsin-Madison have demonstrated for the first time the ability to differentiate human pluripotent stem cells (hPSCs) into various types of blood cells. The new conversion technique, using only four factors, can develop blood cell precursors from any cell in the body.
The stem cells used by the researchers are induced hPSCs, as the precursors can be any cell of the body. Researchers take samples from skin, muscle, inner cheek, or other areas and coax those cells back into a pluripotent state, meaning the cells can become almost any other cell type in the body. Then, using a special combination of factors in a specific order, researchers turn these cells into the desired mature cell type. This approach lessens the ethical quandaries of using embryonic stem cells while still providing the potential for enhanced differentiation and disease treatment.
Normally, the cells are turned into other cells by the use of a viral vector, which implants specific genes into the hPSC to promote differentiation. The researchers at UW instead used transcription factors, which are small proteins that help turn on specific genes that are already present in the cell’s DNA. This approach lessens the concern of using viral delivery, and is much more relevant to actual cellular development. “By overexpressing just two transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo”, says Dr. Igor Slukvin of the Department of Pathology and Laboratory Medicine in the UW School of Medicine and Public Health and the Wisconsin National Primate Research Center.
Cells treated with ETV2 and GATA2 developed into a pan-myeloid lineage, promoting differentiation into granulocytes (cells of the immune system), while cells treated with GATA2 and TAL1 develop into a erythro-megakaryocytic lineage, promoting differentiation into red blood cells and platelets.
Blood cell extraction is an arduous process, complicated in many instances by diseases such as leukemias and lymphomas. Even when isolated, the volume of cells is often inadequate to provide a large enough therapeutic effect. Previous differentiation protocols struggled with conversion efficiency, but Dr. Sluvkin’s group was able to yield 100% conversion with three times the expansion, turning one million hPSCs into thirty million blood cells.
Since the new blood cells will derive from the patient being treated, they will have the same type of DNA and cell surface markers as the patient’s normal blood cells. This will prevent immune rejection, allowing the cells to out compete damaged or diseased cells in ailments such as sickle cell anemia and certain infections.
Edward Marks is a PhD student at the University of Delaware. His research involves the healing of myocardial tissue after major cardiac events using nanomedicine techniques, with the goal of pushing any advancement directly into the clinic. Edward received his BS from Rutgers University and Masters from the University of Delaware.
