Biomedical Engineering Reference
In-Depth Information
of cellular therapies is therefore substantial. Progress in decreasing the costs of these
therapies also will encourage investment into new types of treatments. In this way, new
medical products will be developed to greatly improve the quality of life and productivity
of affected individuals.
The concept of directly engineering tissues was pioneered by Y. C. Fung in 1985. The first
symposium on this topic was organized by Richard Skalak and Fred Fox in 1988, and since
then the field of tissue engineering has grown rapidly. Thousands of scholarly articles have
been written on the topic, and in 1995 a peer-reviewed journal called
was
established. Since that time, the original journal has sprouted into three separate journals
(
Tissue Engineering
) to more broadly cover the field,
and numerous other journals in the topic area have emerged, including the
Part A: Primary Papers
,
Part B: Reviews
, and
Part C: Methods
Journal of Tissue
Engineering and Regenerative Medicine
. The field also has received considerable attention in
the lay press because of the opportunities it presents to revolutionize medicine for an aging
population.
The last two decades have seen remarkable advances in biology that have enabled tangi-
ble progress in tissue engineering. Cutting-edge cell therapies that have reached the
advanced stages of development include various forms of immunotherapies, chondrocytes
for cartilage repair, liver and kidney cells for extracorporeal support devices,
-islet cells for
diabetes, skin cells for patients with ulcers or burns, and genetically modified myocytes for
treatment of muscular dystrophy. In addition, engineered tissues such as blood vessels,
bladders, urethras, and other tissues are rapidly moving toward the clinic. As would be
expected based on tissue complexity, the challenges faced with each tissue are different.
A few examples are provided in the following sections for illustrative purposes.
b
Bone Marrow Transplantation
Bone marrow is the body's most prolific organ. It produces on the order of 400 billion
myeloid cells daily, all of which originate from a small number of pluripotent stem cells
(Figure 6.3). The bone marrow is comprised of 500 to 1,000 billion cells and regenerates
itself every two to three days, which represents normal hematopoietic function. Individuals
under hematopoietic stress, such as systemic infection or sickle cell anemia, will have blood
cell production rates that exceed the basal level. The prolific nature of bone marrow cells
makes it especially susceptible to damage from radio- and chemotherapies. Bone marrow
damage limits the extent of these therapies, and some regimens are fully myoablative. With-
out any hematopoietic support, patients who receive myoablative dose regimens will die
due to hematopoietic failure.
Bone marrow transplantation (BMT) was developed to overcome this problem. In an
autologous setting, the bone marrow is harvested from the patient prior to radio- and
chemotherapies. It is cryopreserved during the time period that the patient undergoes treat-
ment. After chemotherapeutic drug application and several half-lives of the drug have
passed, the bone marrow is rapidly thawed and returned to the patient. The bone marrow
cells are simply introduced into the circulation, and the bone marrow stem cells naturally
“home” to the marrow cavity and reconstitute bone marrow function. In other words, the
hematopoietic tissue is rebuilt in vivo by these cells. This process takes several weeks to
complete, during which time the patient is immunocompromised.
