Biomedical Engineering Reference
In-Depth Information
Yasko, A. W., Lane, J. M., Fellinger, E. J.,
Rosen, V., Wozney, J. M., and Wang, E.
A. (1992). The healing of segmental
bone defects, induced by recombinant
human bone morphogenetic protein
(rhBMP-2). A radiographic, histological,
and biomechanical study in rats.
J. Bone
Joint Surg. Am
. 74: 659-670.
Ye, Q., Zund, G., Jockenhoevel, S.,
Schoeberlein, A., Hoerstrup, S. P.,
Grunenfelder, J., Benedikt, P., and
Turina, M. (2000). Scaffold pre-coating
with human autologous extracellular
matrix for improved cell attachment in
cardiovascular tissue engineering.
ASAIO. J
. 46: 730-733.
Zieske, J. D., Mason, V. S., Wasson, M. E.,
Meunier, S. F., Nolte, C. J., Fukai, N.,
Olsen, B. R., and Parenteau, N. L.
(1994). Basement membrane assembly
and differentiation of cultured
corneal cells: importance of culture
environment and endothelial cell
interaction.
Exp. Cell Res.
214:
621-633.
Zilla, P., Deutsch, M., and Meinhart, J.
(1999). Endothelial cell transplantation.
Semin. Vasc. Surg
. 12: 52-63.
Zimmermann, W. H., Fink, C., Kralisch, D.,
Remmers, U., Weil, J., and
Eschenhagen, T. (2000). Three-
dimensional engineered heart tissue
from neonatal rat cardiac myocytes.
Biotechnol. Bioeng
. 68: 106-114.
Zimmermann, W. H., Schneiderbanger, K.,
Schubert, P., Didie, M., Munzel, F.,
Heubach, J. F., Kostin, S., Neuhuber, W.
L., and Eschenhagen, T. (2002). Tissue
engineering of a differentiated cardiac
muscle construct.
Circ. Res
. 90:
223-230.
Zund, G., Hoerstrup, S. P., Schoeberlein,
A., Lachat, M., Uhlschmid, G., Vogt,
P. R., and Turina, M. (1998). Tissue
engineering: a new approach in
cardiovascular surgery: seeding of human
fibroblasts followed by human
endothelial cells on resorbable mesh.
Eur. J. Cardiothorac. Surg
. 13:
160-164.
Zurn, A. D., Henry, H., Schluep, M.,
Aubert, V., Winkel, L., Eilers, B.,
Bachmann, C., and Aebischer, P. (2000).
Evaluation of an intrathe-cal immune
response in amyotrophic lateral sclerosis
patients implanted with encapsulated
genetically engineered xenogeneic cells.
Cell Transplant
. 9: 471-484.
failing liver. Later applications include the use of encap-
sulated cells for
in situ
synthesis and local delivery of
naturally occurring and recombinant cell products for the
treatment of chronic pain, Parkinson's disease, macular
degeneration, and similar disorders. Devices employed
for encapsulated cell therapy vary in size over several
orders of magnitude from small spheres, with a volume
of 10
-5
cm
3
, to large extracorporeal devices with a net
volume of w10 cm
3
. Their anticipated service life ranges
from a few hours in the case of the liver to several years
for other therapeutic implants. In some cases, the
immunoisolatory vehicles simply serve as constitutive
sources of bioactive molecules; in other cases, regulated
release is required; and for still others, host de-
toxification is the goal. Despite such a spectrum of ap-
plication parameters, devices containing immunoisolated
cells share many common features and design principles:
(1) Cells are rarely deployed more than 500
m
m(5
10
-2
cm) from the host; cells much farther than this critical
distance either undergo necrosis or cease to synthesize
and release protein. (2) Cells generally are supported on
a matrix or scaffold to provide some of the functions of
normal extracellular matrix and to prevent the formation
of large, unvascularized cellular aggregates. (3) Sep-
arative membranes are invariably self-supporting, thus
requiring a design trade-off between transport charac-
teristics and mechanical strength. (4) Both the mem-
brane and the matrices usually are prepared from either
hydrogels or reticulated foams, themselves chosen from
relatively few among the many available candidates.
In the remainder of this overview, we will describe
the immunological challenge of protecting cells with
barrier
7.1.3 Immunoisolation
Michael J. Lysaght and David Rein
Introduction
In the context of tissue engineering and cellular medi-
cine, the terms
immunoisolation
and
encapsulation
usu-
ally refer to devices and therapies in which living cells are
separated from a host by a selective membrane barrier.
This barrier permits bidirectional trafficking of small
molecules between host and grafted cells, and protects
foreign cells from effector agents of a host's immune
system. In analogy with pharmacological immunosup-
pression, the degree of protection afforded by immu-
noisolatory barriers depends upon the circumstances of
application and may be total or partial, long-term or
short-term. Occasional reference to the concept, which
is illustrated in
Fig. 7.1.3-1
, can be found as early as the
late 1930s and appears sporadically in the literature of
the 1950s and 1960s. The approach first received serious
investigational attention in the mid-1970s. Interest has
expanded considerably in the past two decades. Encap-
sulation currently encompasses a daunting array of ther-
apy formats, device configurations, and biomaterials.
The first modern efforts involving cell encapsulation
were directed at development of a long-term implant to
replace the endocrine function of a diabetic pancreas.
Other investigators quickly expanded this field of study
to include short-term extracorporeal replacement of the
materials;
summarize
critical
components
of
