Stem Cells and Regenerative Biology

All cells in our body have a repertoire of approximately 40,000 genes upon which to draw, but at any moment in time, only about one-quarter of these genes (10,000) are turned on (expressed). The fundamental basis for differences in the various types of cells (heart, brain, liver, skin) that comprise our body is found in the cell's decision as to which genes it turns-on and which genes it represses. During fetal development, embryonic stem cells with full access to the genome give rise to the multitude of cell types required for formation of a complete individual, spinning out progeny with progressively restricted access to the genome which are committed to certain cellular fates.

It is now recognized that the adult body contains reservoirs of residual stem cells resembling the primitive cells of the embryo, and that these cells may have the capacity to be instructed to produce a panoply of cell types for therapeutic benefit. Technologies for returning full access to the genome of mature, differentiated cells are also rapidly being developed, forecasting a day when almost any cell might make suitable starting material for re-programming to produce cells with stem cell-like qualities.

The need for progress in cell and organ replacement therapies is already acute and growing, as society trends towards a more aged population. Furthermore, it is clear that many diseases simply cannot be cured by small-molecule drugs, including Type I diabetes, Parkinson’s Disease, liver failure, and cartilage deterioration (degenerative joint disease). For these diseases, therapies based on introduction of replacement cells or organs are the keys to progress.

The overall goal of the Stem Cell Biology and Regenerative Biology program is to promote regeneration of tissues in disease and normal aging. Progress in this area of “regenerative medicine” will depend on progress in stem cell biology and will require development of expertise and technology in the isolation, culture, and manipulation of cells with the capacity to differentiate into various cell types. Recent research suggests that a single or a few classes of stem cells reside in many adult tissues, and that environmental signals determine how these cells differentiate. It will be important to determine what those signals are. In this regard, the Institute has a long tradition of working on mouse embryonic stem cells and differentiation developmental biology, which lays the foundation for this initiative.

Scientists collaborating within this Program have recently demonstrated that cells within the bone marrow of adult mice (mammals) are constantly migrating into the brain and producing new nerve cells. Though occurring in very small numbers, this seminal observation suggests the existence of a naturally occurring pathway for regeneration of the nervous system, and forecasts a day when drugs might be developed to boost the endogenous production of new brain cells from the bone marrow. Sanford-Burnham Institute researchers have also identified a gene regulator (transcription factor) that operates as a master-switch in stem cells, driving them to become brain cells (neurons). Studies of muscle stem cells by scientists affiliated with this Program have also provided an animal (mouse) model for testing cell replacement therapies for muscular dystrophies. Engineering cell replacement therapies for restoration of insulin-producing cells in patients with Type I diabetes is another goal of this Program.