Biomedical Engineering Reference
In-Depth Information
Tissues are comprised of multiple cell types that interact dynamically with each other.
Therefore, tissue-specific functions are often observed only with cocultures of those multi-
ple cell types or with cultures of a particular cell type in combination with the signals from
the others. Those signals include insoluble factors in the extracellular matrix, signals from
direct cell-cell contact, and soluble signals from autocrine, paracrine, and endocrine interac-
tions. To use these signals as bioengineers, several basic concepts in cell biology need to be
understood and quantitatively characterized. These include the key cellular processes of
cell differentiation, hyperplastic and hypertrophic growth, migration (motion), protein syn-
thesis, and death (necrosis or apoptosis), all of which combine to define tissue function.
Basic information about stem cell and maturational lineage biology and the role of deter-
mined stem cells in organ function, genesis, and repair will be presented.
The creation of new engineered tissues requires that many bioengineering challenges
be met. For example, bioengineering considerations in cell therapies include injection
needle design and procedure protocols. For this application, needles must be optimized
to reduce shear stress on cell membranes. Nutrient mass transfer must be analyzed to deter-
mine the range of cell aggregate sizes that can be sustained as viable tissues.
Engraftment
techniques and seed site selection criteria must be established so cells will prosper and
assist in system homeostasis. Detrimental events, such as the formation of emboli, need to
be prevented. For more complex implantable devices and bioreactors, other challenges
will be faced. In these systems, the function, choice, manufacturing, and treatment of bio-
materials are important for cell growth and device construction. Fluid mechanics and mass
transfer play important roles in normal tissue function and therefore become critical issues
in ex vivo cellular device designs. System analysis of metabolism, cell-cell communication,
and other cellular processes can be used to define bioartificial organ specifications. A prop-
erly designed ex vivo culture system must appropriately balance the rates of biological and
physicochemical processes to obtain desired tissue functions. By mathematically modeling
this balancing effect, dimensionless parameter groups can be formulated that describe charac-
teristic ratios of time constants. In this way, new dimensionless values will evolve to relate
ratios of “physical times” with “biological times.”
Finally, the implementation of cell therapies and tissue grafts in the clinic requires
the recognition and resolution of several difficult issues. These include tissue harvest, cell
processing and isolation, safety testing, cell activation/differentiation, assay and medium
development, storage and stability, and quality assurance and quality control issues. These
challenges will be described in this chapter but are not analyzed in detail.
6.1.3 Human Cells and Grafts as Therapeutic Agents
Cell therapies use human cells as therapeutic agents to alleviate a pathological condition.
It is important to note that some cell therapies are already an established part of medical care.
One existing type of cell therapy is blood transfusion, which has been practiced for decades
with great therapeutic benefit. This therapy uses red blood cells (RBC) as the transplant prod-
uct into anemic patients to help to restore adequate oxygen transport. Similarly, platelets
have been transfused successfully into patients who have blood clotting problems. Bone
marrow transplantation (
BMT
) has been practiced for almost two decades, with tens of
thousands of cancer patients undergoing high-dose chemo- and radiotherapies followed by
