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JOSÉ LUIS PEDRAZ y GORKA ORIVE AN. R. ACAD. NAC. FARM.

the potential impact of this field is still far broader, the past few years have seen
several firsts which has brought the whole technology much closer to a realistic
proposal for clinical application.

Key words: Microcapsule.— Cell.— Encapsulation.— Biotechnology.

EXTENSIVE ABSTRACT

In the past decades, much effort has been focused on the development of im-
munoisolation technologies for the long-term transplantation of biologically active
molecules to restore or improve native tissue function. The potential impact of
these technologies from a therapeutic and economic standpoint of view is enor-
mous since chronic administration of immunosuppressants and implementation of
strict immunosuppressive protocols might be eliminated, thereby facilitating pa-
tients´ life quality.

Microcapsules are probably the current preferable system for cell transplanta-
tion and represent an exciting biotechnological approach for both organ replace-
ment and continuous and controlled drug delivery. The concept of cell microen-
capsulation is in theory fairly simple. It consists of enclosing the biologically active
material within a polymeric matrix surrounded by a semipermeable membrane
that is designed to circumvent immune rejection. This membrane allows the bi-
directional diffusion of nutrients, oxygen and waste, yet prevents immune cells and
antibodies, which might destroy the enclosed cells, from entering. In this way, it
is possible to maintain the long-term function of the transplant in a sequestered
environment.

In light of increasing incidence of age-related diseases and the current despe-
rate shortage of donor organs, the hope that encapsulated cells may be used as
therapeutics seems increasingly to be realized. Furthermore, the potential of this
approach includes encapsulated cells which supply the host with regulated and/or
continuous «de novo» delivery of therapeutic product. These artificial cells can be
transplanted into a variety of tissues and organs, making the technology suitable
for a local (solid tumors), regional (brain), oral or systemic delivery (intraperito-
neal) of therapeutics. When long-term continuous delivery of therapeutics is requi-
red, the cost of encapsulated cells may be off-set by the cost of the therapeutic
product. Further, the same capsule chemistries could be used for a large number
of patients regardless of the Human Leukocyte Antigen (HLA), making this appro-
ach cost-effective.

Recent progress in the field has brought the whole technology much closer to
a realistic proposal for clinical application. In fact, the results achieved from small
and large animal models have provided the scientific basis for several clinical trials
including the encapsulation of allogeneic islets for the treatment of diabetes, or the
most recent immobilization of cytochrome P450 enzyme expressing cells for the
eradication of pancreatic cancer.

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