Biomedical Engineering Reference
In-Depth Information
6.2.3 Models for Stem Cell Proliferative Behavior
It should be clear by now that the replication functions of stem cells are critical to tissue
function and tissue engineering. How do stem cells divide, and what happens when they
divide? Three models describe the dynamic behavior of the stem cell population.
The Clonal Succession Concept
Cellular systems are maintained by a reservoir of cells that either grows very slowly or
may be in a dormant state. In these cases, the reservoir of cells is available throughout
the tissue's lifespan and can be routinely challenged to enter the complex process of cell
proliferation and differentiation. Once triggered, such a stem cell would give rise to a large
clonal population of mature cells. Any one of these clones would now have a limited life
span, since feedback signals dissipate the need to maintain cell production fluxes. After
time, such a clone will “burn out,” and, if needed, a new stem cell clone would take over
the cell production role.
Deterministic Self-Maintenance and Self-Renewal
This model relies on an assumption that stem cells can self-replicate. Following a stem
cell division, there is a 50 percent probability that one of the daughter cells maintains the
stem cell characteristics, while the other undergoes differentiation. The probability of self-
renewal is regulated and may not be exactly 50 percent, depending on the dynamic state
of the tissue.
Stochastic Models
This model considers that the progeny of a stem cell division can generate zero, one, or
two stem cells as daughter cells (notice that the clonal succession model assumes zero, and
the deterministic model assumes one). The assumption is that each of the three outcomes
has a particular property.
6.2.4 Stem Cells and Tissue Engineering
Stem Cells Build Tissues
Stem cells are the source of the cells that make up all tissues in the body during develop-
ment. In addition, certain tissues in adults have reservoirs of resident stem cells that can be
mobilized to repair damage when needed. Thus, stem cells build and maintain tissues
in vivo and are of great interest because of their potential use to also generate tissue ex vivo.
The use of stem cells in tissue engineering has rapidly gained momentum because of their
very high proliferative capacity and ability to differentiate into multiple cell types.
Ex Vivo Growth and Manipulation of Stem Cells
The classical definition of a stem cell holds that it has both the ability to divide into a new
stem cell without differentiating and to differentiate into a specialized cell type. This makes
stem cells attractive as a cell source for tissue engineering because the number of stem
cells can be expanded greatly before they are differentiated toward a specific tissue lineage.
This scenario offers a theoretically inexhaustible source of cells with which to create new
tissues. However, the ex vivo conditions for truly self-replicative expansion have not been
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