2004 Directors' Summary Synopsis

STEM CELL BIOLOGY

The study of stem cells is one of the most exciting, controversial, and debated fields in science today. One of the goals in Miami Project laboratories is to learn how stem cells can be "turned on" to replace damaged neurons. Researchers at The Miami Project have undertaken work to define how neurogenesis – the formation of new neurons – is regulated in both embryonic and adult neural stem cells (NSCs).

One replacement strategy may involve triggering stem cells within the nervous system to move to and mature in the injured area. Recent research suggests that, throughout life, the adult brain retains a limited capacity to make new neurons. Two specific areas in the brain contain NSCs and are known to generate new neurons. Dr. Daniel Liebl and his colleagues have been conducting studies to understand how various molecules influence the transformation of adult neural stem cells to nerve cells. Their studies suggest a family of molecules, the ephrins, may play an important role in triggering adult neurogenesis.

Another cell replacement strategy may involve manipulation of stem cells in culture dishes prior to transplantation. Drs. Pantelis Tsoulfas and Patrick Wood have been involved in studies to gain understanding of the types of cell-signaling events that influence the differentiation of embryonic stem cells (ESCs) into specific families of cells. In a recent study, he and his colleagues examined a group of proteins called bone morphogenetic proteins (BMP) and found that this family of proteins helps ESCs to transform into a variety of cells found in the developing nervous system. With continuing research, they hope to determine specific genetic and molecular cues for the manipulation of stem cells into specific and useful cell types.

In addition to identifying in vitro techniques that will push stem cells to neurogenesis, it is also important to assure that transplanted cells survive. Preliminary studies of the transplantation of stem cells into the adult nervous system have shown that the transplanted cells rarely survive in sufficient quantities and rarely differentiate into desired neurons. One reason for their poor survival is the damaged nervous system lacks neurotrophic factors that provide nourishment to the cells. Dr. Jacqueline Sagen and her colleagues have examined an approach to this problem and their findings suggest that the transplantation of chromaffin cells along with stem cells enhances their survival. Chromaffin cells produce several neurotrophic agents that may aid in neuroprotection, survival of stem cells, and their differentiation more toward neurons.

Scientists believe if the development of stem cells into mature nerve cells can be achieved, they may become a useful source to replace cells in a variety of nervous system disorders. The basic goals of stem cell research in Miami Project laboratories is to understand and influence how these cells transform into specific families of cells and to test their usefulness in animal models of SCI.