Stem Cell Biology and Bioengineering Laboratory
Embryogenesis, the maturation of a small inner cell mass into tissues and then into organ systems that comprise a living organism, is a complex developmental process involving coordinated cues that direct cell behavior. Tissue engineering and regenerative medicine attempt to recapitulate that developmental process within an engineered scaffold, but with varying degrees of success to date. One major stumbling block has been our lack of understanding of the in vivo microenvironments for specific cell types, making it difficult to mimic development with functional engineered tissue constructs or engineered “smart cells.” Our group explores how these microenvironments affect stem cell niches.To understand how such processes might occur, it is important to have a fundamental grasp on what stem cells are. First, they are uncommitted cells, i.e. not a specific type of cell such as a muscle or bone cell. These cells undergo 'self-renewal' in that they can propogate themselves for long periods through cell division, unlike most cells that are of a specific type. Secondly, they can mature into a variety of specific types of cells such as the beating heart muscle cells, neurons in the brain or endothelial cells that line blood vessels. All of these cells are highly specialize but they all originated from a common pool of cells during development. Our group primarily works with two kinds of stem cells (both from animals and humans): embryonic stem cells and mesenchymal stem cells, which have different functions and characteristics. Embryonic Stem Cells, or ES cells, are derived from the 'blastocyst,' a small cluster of cells that forms 3 to 5 days post-fertilization. Mesenchymal Stem Cells, or MSCs, are derived from the bone marrow of adult patients. While ES cells are "pluripotent," meaning they can form almost any tissue in the body, MSCs are "multipotent" in that they are limited to become only specific types of cells (bone, muscle, etc). NIH has a wonderful website for further information on stem cells.
Our group wants to study these types of stem cells so that we can better understand what differentiates these cells from specialized cell types with the goal of being able to direct the behavior of these cells in cell-based therapies, such as stem cell injections into the heart muscle of heart attack patients to regenerate muscle (called "Cellular Cardiomyoplasty"). The cue that we primarily use to direct stem cell behavior is the extracellular matrix, or ECM, a network of fibrous proteins that surround cells and provide sites for cell attachment. This network is comprised mainly of long polymer-like proteins, namely collagen, fibronectin, and laminin, which can send cells biochemical, mechanical, topographical, and patterning cues among others, all of which influence how a stem cell behaves and matures into a specific type of cell.
Scanning electron micrograph of cells embedded in a fibrous extracellular matrix.
(From T. Nishida et al., Invest. Ophthalmol. Vis. Sci. 29:1887–1890, 1988. © Association for Research in Vision and Opthalmology.)
Embryonic Stem Cells
Mesenchymal Stem Cells
Department of Bioengineering
University of California, San Diego