Biomedical Engineering Reference
In-Depth Information
the hand versus that on the face). The dermis is a connective tissue layer under the basal
lamina and is comprised primarily of fibroblasts (also called stroma). The epidermis con-
sists of multiple layers of epithelia comprised of differentiating keratinocytes, with the least
differentiated cells located at the basal lamina. Thin skin has a squamous columnar organi-
zation (each column about 30
m in diameter). A stem cell compartment has been identified
in the deep pockets within the epidermis/dermis undulations and also in bulges near hair
follicles. The stem cells produce committed
progenitors
, also called “transit amplifying
cells,” which migrate into the shallow pockets and from there into cells that line the entire
basal lamina. Only epidermal cells adherent to the basal lamina are cycling, while cells that
lose their attachment to the basal lamina move upward and differentiate into succeeding
stages of cells. Ultimately, they turn into granular cells, and then into keratinized squames
that eventually flake off. Keratins are proteins defining the differentiated cells of the skin
and are evident in many forms—from forms that provide skin mechanical protection to
those that are present in body hair (or in feathers in birds or scales in other vertebrates).
The net proliferative rate of skin depends on the region of the body. In particular the turn-
over of skin is on the order of a few weeks.
m
The Liver
The liver is a maturational lineage system, including a stem cell compartment, that is
analogous to those in the bone marrow, skin, and gut. The liver's lineage is organized
physically within the acinus, the structural and functional unit of the liver. In cross
section, the acinus is organized like a wheel around two distinct vascular beds: six sets
of portal triads, each with a portal venule, hepatic arteriole, and a bile duct, form the
periphery, and the central vein forms the hub. The parenchyma, effectively the “spokes”
of the wheel, consist of plates of cells lined on both sides by the fenestrated sinusoidal
endothelium. By convention, the liver is demarcated into three zones: zone 1 is periportal;
zone 2 is midacinar; and zone 3 is pericentral. Blood flows from the portal venules and
hepatic arterioles at the portal triads, through sinusoids that line plates of parenchyma,
to the terminal hepatic venules and into the central vein. The stem cell compartment is
present around the portal triads, zone 1, and identified in anatomical entities called
Canals of Hering. The stem cells of the liver are at least bipotent and produce daughter
cells that become either biliary cells (bile duct epithelia) or hepatocytes. Hepatocytes
display marked morphologic, biochemical, and functional heterogeneity based on their
zonal location. The size of hepatocytes increases from zone 1 to zone 3, and one can
observe distinctive zonal variations in morphological features of the cells, such as mito-
chondria, endoplasmic reticulum, and glycogen granules. Hepatocytes show dramatic
differences in DNA content from zone 1 to zone 3, with periportal cells being diploid
and midacinar to pericentral cells shifting toward polyploid distinctions. Octaploid cells
in the pericentral zone show evidence of apoptosis. Adult rodent livers (rats and mice)
are 90 to 95 percent polyploid; adult human livers are 40 to 50 percent polyploid,
whereas fetal and neonatal liver cells are entirely diploid. The transition to adult ploidy
patterns is observed by age 3 to 4 weeks in rats and mice, and by late teenage years in
humans. With age, the liver becomes increasingly polyploid in all mammalian species
surveyed. This may help to explain the reduction in regenerative capacity of the liver
with age.
