Biomedical Engineering Reference
In-Depth Information
Stem cells are dependent on signals from age- and tissue-specific stroma. The signals from
the stroma are only partially defined but include signals such as Leukemia Inhibitory
Factor (LIF), various fibroblast growth factors or FGFs, and various interleukins (e.g., IL 8,
IL11).
The most poorly understood of all the signals defining the stem cell niche(s) are those from
feedback loops, which are initiated from mature cells, and where these signals inhibit
stem cell proliferation. Implicit evidence for feedback loops is that cell expansion ex vivo
requires separation between cells capable of cell division (the diploid subpopulations)
and the mature nonproliferating cells.
Which tissues have stem cells?
For decades it was assumed that stem cell compartments exist only in the rapidly prolifer-
ating tissues such as skin, bone marrow, and intestine. Now, there is increasing evidence that
essentially all tissues have stem cell compartments, even the central nervous system. There
are now numerous reports of the isolation and characterization of tissue-specific stem cells,
and they are actively being investigated as a potential cell source for tissue engineering.
The Roles of Stem Cells
The stem cell compartment of a tissue is the fundamental source of cells for turnover and
regenerative processes. Stem cell commitment initiates cell replacement and genesis of the
tissue, resulting in tissue repair and maintenance of tissue functions. Stem cell depletion
due to disease or toxic influences (e.g., drugs) eventually leads to partial or complete loss
of organ function. Mutational events affecting the stem cells can result in tumors for which
both altered and normal stem cells are actively present. Thus, tumors are now considered
transformed stem cells, an idea originally proposed by Van Potter, Sell, and Pierce, and
now confirmed by current stem cell biologists.
6.2.2 The Maturational Lineages of Tissues
All stem cells are pluripotent, giving rise to multiple, distinct lineages of daughter
cells that differentiate, stepwise, into all of the mature cells of the tissue. A general model
for the production of mature cells arising from tissue-specific stem cells is shown in
Figure 6.9. Determined stem cells (pluripotent) replicate slowly in vivo, with rates influ-
enced by various systemic signals. Their immediate descendants are committed progenitors
(unipotent) capable of rapid proliferation and shown in some tissues (e.g., skin) to be the
acute responders to mild to moderate regenerative stimuli. The unipotent progenitors
mature in a stepwise fashion through intermediate stages into fully mature cells. Character-
istically, various tissue-specific functions are expressed in cells throughout the maturational
lineage and in a lineage-dependent fashion. One can generalize about these gradual pheno-
typic changes by categorizing the functions as “early,” “intermediate,” and “late” taskings.
In some cases, a specific gene is expressed uniquely only at a specific stage. In others, there
are isoforms of genes that are expressed in a pattern along the maturational lineage, while
in yet others there are changes in the levels of expression of the gene. Finally, the cells
progress to senescence, a phenomena that typifys aging cells. The maturation of the cells
is dictated in part by mechanisms inherent in the cells (e.g., changes in the chromatin)
