Biomedical Engineering Reference
In-Depth Information
factors, nutritional supplements, and basal media containing specific concentrations of
calcium, trace elements, and gases. Reviews of these conditions for many cell types are
available in recently published textbooks and journal articles.
6.2 BIOLOGICAL CONSIDERATIONS
6.2.1 Stem Cells
It is now thought that essentially all tissues contain stem cell populations that can
produce cellular progeny that differentiate into mature tissue phenotypes. The maturational
process includes two branches: the “commitment“ branch, in which pluripotent stem cells
produce daughter cells with restricted genetic potentials appropriate for a single set of cell
activities (unipotent), and the “differentiation” branch, in which sets of genes are activated
and/or altered in their levels of expression. The following sections discuss how these major
tissue subdivisions work together to generate or repair tissues in order to provide tissue
functions.
Stem Cells and the “Niche” Hypothesis
Pluripotent stem cells are cells that are capable of producing daughter cells with more
than one fate; they can self-replicate, and they have the ability to produce daughter cells
identical to the parent. Totipotent stem cells are cells that can generate all the cell types
of the organism. Determined stem cells are cells in which the genetic potential is restricted
to a subset of possible fates; they can produce some, but not all, of the cell types in the
organism.
Determined stem cells of the skin can produce all the cell types in the skin but not those
of the heart. Similarly, determined stem cells of the liver can produce all liver cell types but
not brain. The lay press often refers to determined stem cells as “adult stem cells,” which is
a misnomer because determined stem cells are present in fetal and adult tissue. The deter-
mined stem cells give rise to unipotent progenitors, also called committed progenitors, with
genetic potential restricted to only one fate. These unipotent progenitors rapidly proliferate
into large numbers of cells that then differentiate to mature cells. The stem cells and the
unipotent progenitors are the normal counterparts to tumor cells and to immortalized
cell lines. Determined stem cells identified to date are small in size (typical diameters of
6-10
m), have a high nucleus to cytoplasmic ratio (blast-like cells), and express certain
early genes (e.g., alpha-fetoprotein) and antigens (e.g., CD34, CD117). They have chromatin
that binds particular dyes at levels lower than that of the chromatin in mature cells,
enabling them to be isolated as “side-pocket” cells using flow cytometric technologies. Stem
cells express an enzyme, telomerase, that maintains the telomeres of their chromosomes at
constant length, a factor in their ability to divide indefinitely in vivo and ex vivo. Multiple
parameters must be used to permit isolation and purification of any determined stem cell
type, since there is no one parameter (antigen, size, cell density) sufficient to define any
determined stem cells. Furthermore, they appear to grow very slowly in vivo and may
commit to growth and differentiation in a stochastic manner. A first-order rate constant
for hemopoietic stem cells is about one day and their cycling times have been measured
m
