Biomedical Engineering Reference
In-Depth Information
by means of time-lapse videography. They commit to differentiation in culture. The first
and second doubling take about 60 hours, and then the cycling rate speeds up to about
24 hours cycling time. By the fifth and sixth doubling, they are dividing at a maximal rate
of 12 to 14 hours doubling time.
What evidence is there that stem cells exist?
Lethally irradiated mice that would otherwise die from complete hematopoietic failure
can be rescued with as few as 20 selected stem cells. These animals reconstitute the multiple
lineages of hematopoiesis as predicted by the stem cell model. In sublethally irradiated
animals, genetically marked mesenchymal stem cells found in bone marrow will give rise
to cells in multiple organs over a long time period. These investigations and many others
have established conclusively the presence of stem cells, their multilineage potential, and
their ability to persist over long periods of time in vivo.
Stem Cell Niches
The field of stem cell niches is rapidly expanding due to its importance in regulating
stem cell fate. The goal is to define and understand the local microenvironment of the stem
cell compartment. The field is still new but already has yielded generalizations that are
proving to be useful guides for defining ex vivo expansion conditions for the cells:
Stem cells do not have the enzymatic machinery to generate all their lipid derivatives
from single lipid sources and so require complex mixtures of lipids for survival and
functioning.
Calcium concentrations are quite critical in defining whether stem cells will expand or
undergo
differentiation. The mechanisms underlying the phenomenology are poorly
understood.
Specific trace elements, such as copper, can cause more rapid differentiation of some
determined stem cell types. It is unknown whether this applies to all stem cells, and the
mechanism(s) is not known.
Specific mixtures of hormones and growth factors are required, with the most common
requirements being insulin and transferrin/Fe. Addition of other factors can result in
expansion of committed progenitors and/or lineage restriction of the stem cells toward
specific fates.
The matrix chemistry of known stem cell compartments consists of age-specific and
cell-type-specific cell adhesion molecules, laminins, embryonic collagens (e.g., type
III and IV collagen), hyaluronans, and certain embryonic/fetal proteoglycans. With
maturation of the stem cells toward specific cell fates, the matrix chemistry changes
in a gradient fashion toward one typical for the mature cells. Although the matrix
chemistry of the mature cells is unique for each cell type, a general pattern is the
inclusion of adult-specific cell adhesion molecules, various fibrillar collagens (e.g., type I,
II collagen), fibronectins, and adult-specific proteoglycans. A major variant is that for
skin and neuronal cells, in which mature cells lose expression of collagens, fibronectins,
and laminin. Additionally, the matrix chemistry of these cell types is dominated by
CAMs and proteoglycans.
