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Encyclopedia of Physical Science and Technology EN016J-783 August 1, 2001 10:58

Tissue Engineering 841

months to a year, although the reliability of the procedure Another source of stem cells is embryos, which can be
is far from perfect. A common recurrent problem with obtained at the blastocyst stage. Embryonic stem cells are
immuno-isolated cells is the presence of a foreign-body totipotent, meaning that they have the potential to differ-
reaction against the capsule material itself, leading to the entiate into any cell type found in the body. In the presence
generation, over a period of days to weeks, of a fibrotic of leukemia inhibitory factor, embryonic stem cells self-
layer around it, compromising nutrient transport and the renew without any loss of development potential. Other-
release of insulin from the implanted cells. Besides im- wise, they differentiate into a wide variety of cell types,
provements in the biocompatibility of the material, one the nature of which depends on the specific factors added
avenue that may improve function of these devices is the to the culture medium. Cloning techniques enable replac-
use of materials and/or factors promoting the growth of ing the original DNA from the embryonic stem cell with
blood vessels near the surface of the capsule. that of a patient (extracted from one of the patient’s cells
It has also been suggested that the longevity of islet cells such as skin). The availability of such cells could have
may be limited in encapsulated systems, and that integra- important implications for engineering tissues made of
tion into the host tissue may be necessary for a permanent cells that have typically lost their ability to replicate, such
cure. Thus, as an alternative to immuno-isolation, other as neurons, lung epithelium, etc. However, serious ethi-
approaches are currently being sought to either eliminate cal considerations will have to be resolved prior to using
the antigenic proteins and polysaccharide moieties on im- human embryonic stem cells in such applications. Fur-
planted cells or interfere with the signaling pathways gov- thermore, more progress is needed in order to increase the
erning these immune responses. These studies are in fact yield of specific cell types used in tissue engineering from
not limited to tissue-engineered constructs, but are also stem cells.
under investigation for the transplantation of whole or- Clinical applications for engineered tissues often re-
gans. For example, transgenic strains of pigs, which have quire a readily available supply of a large number of cells
a body size similar to a human and which express human when the need arises. Maintaining a continuous supply by
surface antigens, are currently being developed. culture techniques or obtaining fresh cells in large num-
bers from animal or human sources is clearly impractical.
Thus, long-term preservation methods will be critical for
IV. FUTURE PROSPECTS FOR the future clinical applications of tissue engineering. Cry-
TISSUE ENGINEERING opreservation is the most efficient method of preservation,
and careful studies of the effects of freezing-associated os-
Tissue engineering is a relatively new and rapidly evolv- motic, chemical, thermal, and mechnical stresses will be
ing field still in its infancy. Exciting new discoveries in required. Although many such studies have been carried
biology will soon open new avenues for tissue engineers. out on dissociated cells in suspension, there have been
One of these discoveries is the recent identification of stem few studies on tissue constructs, which pose special chal-
cells. Stem cells have a high replication potential and can lenges because the optimal freezing conditions for dif-
differentiate into a large number of different cell types. ferent cell types may not be the same, and the freezing
The best characterized stem cells are those of hematopoi- conditions may be difficult to control uniformly in a three-
etic origin that populate the bone marrow. These cells are dimensional system.
also found in very small numbers in the peripheral circu- In summary, tissue engineering encompasses a wide
lation. They have been cultured successfully in vitro on spectrum of disciplines, including biological and chemical
a stromal layer of connective tissue cells to produce all sciences, engineering sciences, and medicine. Although
common blood cell lineages, including red blood cells, tissue engineering is a relatively new field, exciting appli-
monocytes, lymphocytes, and platelets. More recent dis- cations, varying from artificial skin to treat severe burns
coveries suggest that wound healing in specialized tis- patients to a bioartificial pancreas to treat diabetics, have
sues such as muscle sometimes involves the homing of in some cases reached standard clinical practice, and in
stem cells present in the circulation. While the exact na- others shown major advances and promising preliminary
ture of these cells remains to be elucidated, they open clinical results. Thus, it is not unreasonable to expect that
up exciting avenues for tissue engineering. For example, a number of new tissue engineering approaches will enter
such stem cells could be harvested from a patient’s blood, the realm of clinical applications within the next decade.
(requiring a minimally invasive procedure), grown, dif- However, it should be borne in mind that clinical suc-
ferentiated in vitro into the tissue type needed, and then cess relies heavily on our fundamental understanding of
implanted back into the patient. Since patients would re- the many complex issues associated with reconstruction
ceive their own cells, no immune suppression would be and modification of tissues as well as the development of
needed. reliable technologies for large-scale handling of tissues.