Biomedical Engineering Reference
In-Depth Information
vascular supply and the stroma provided by the host tissue
as a matrix for attachment and reorganization (
Matas
et al.
, 1976
). This method offers opportunities for
a number of applications in replacing metabolic functions
as occurs in liver disease, for example (
Grossman
et al.,
1994
). However, cell mass sufficient to replace lost met-
abolic functions is difficult to achieve and its application
for replacing functions of structural tissues such as heart
valves or cartilage is rather limited. Several cell types may
be used for injection, such as bone marrow cells, blood-
derived progenitor cells, and muscle satellite cells (see
also the later subsection on tissue engineering of muscle).
Whole bone marrow contains multipotent mesen-
chymal stem cells (marrow stromal cells) that are de-
rived from somatic mesoderm and are involved in the
self-maintenance and repair of various mesenchymal
tissues. These cells can be induced
in vitro
and
in vivo
to
differentiate into cells of mesenchymal lineage, including
fat, cartilage and bone, and cardiac and skeletal muscle.
The first successful allogenic bone marrow transplant in
a human was carried out in 1968. More than 40,000
transplants (from bone marrow, peripheral blood, or
umbilical cord blood) were carried out worldwide in
2000 (
http://www.ibmtr.org/newsletter/pdf/2002Feb.
pdf
). The most common indications for allotransplants
are acute and chronic leukemias, myelodysplasia (MDS),
and nonmalignant diseases (aplastic anemia, immune
deficiencies, inherited metabolic disorders). Autotrans-
plants are generally used for non-Hodgkin's lymphoma
(NHL), multiple myeloma (MM), Hodgkin's lymphoma,
and solid tumors.
Experimental studies suggested that bone marrow-
derived or blood-derived progenitor cells may also con-
tribute, e.g., to the regeneration of infarcted myocardium
(
Orlic
et al.
, 2001a
).
Tissue Engineering
Blood
flow
Extravascular
compartments
Macrocapsules
sheaths, rods, discs
Microcapsules
spherical
dispersions
Pores
Fig. 7.1.2-1 Configurations of implantable closed-system devices
for cell transplantation. (Reprinted with permission from Langer,
R., and Vacanti, J. P., 1993. Science 260: 920-926.)
blood flows through, it can absorb substances secreted by
the therapeutic cells while the blood provides oxygen and
nutrients to the cells. In macroencapsulation systems,
a semipermeable membrane is used to encapsulate a rel-
atively large (up to 50-100 million per unit) number of
transplanted cells. Microcapsules are basically micro-
droplets of hydrogel with a diameter of less than 0.5 mm
housing smaller numbers of cells. Macrocapsules are far
more durable than microcapsule droplets and can be
designed to be refillable in the body. Moreover, they can
be retrieved, providing opportunities for more control
than microcapsules. Their main limitation is the number
of cells they can accommodate. In animal experiments,
implantable closed-system configurations have been
successfully used for the treatment of Parkinson's disease
as well as diabetes mellitus (
Aebischer
et al.
, 1991
, 1988;
Kordower
et al.
, 1995;
Date
et al.
, 2000
). If islets of
Langerhans are used, they will match the insulin released
to the concentration of glucose in the blood. This has
been successfully demonstrated in small and large ani-
mals with maintenance of normoglycemia even in long-
term experiments (
Kin
et al.
, 2002
;
Lacy
et al.
, 1991
;
Lanza
et al.
, 1999
;
Sullivan
et al.
, 1991
). Major draw-
backs of these systems are fibrous tissue overgrowth and
resultant impaired diffusion of metabolic products, nu-
trients, and wastes, as well as the induction of a foreign-
body reaction with macrophage activation resulting in
destruction of the transplanted cells within the capsule
(
Wiegand
et al.
, 1993
).
Closed-system method
Closed systems can be either implanted or used as ex-
tracorporeal devices. In this approach, cells are isolated
from the body by a semipermeable membrane that
allows diffusion of nutrients and the secreted cell prod-
ucts but prevents large entities such as antibodies, com-
plement factors, or other immunocompetent cells from
destroying the isolated cells. Protection is also provided
to the recipient when potentially pathological (e.g., tu-
morigenic) cells are transplanted. Implantable systems
(encapsulation systems) come in a variety of configura-
tions, basically consisting of a matrix that cushions the
cells and supports their survival and function and a sur-
rounding porous membrane (
Fig. 7.1.2-1
). In vascular-
type designs the transplanted secretory cells are housed
in a chamber around a vascular conduit separated from
the bloodstream by a semipermeable membrane. As
