Nanoporous microsystems for islet cell replacement
Tejal A. Desai
a,
*
, Teri West
b
, Michael Cohen
b
,
Tony Boiarski
b
, Arfaan Rampersaud
b
a
Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 USA
b
IMEDD Inc., Columbus, OH 43212, USA
Received 1 August 2003; accepted 15 May 2004
Available online 23 July 2004
Abstract
The inadequacy of conventional insulin therapy for the treatment of Type I diabetes has stimulated research on several
therapeutic alternatives, including insulin pumps and controlled release systems for insulin. One of the most physiological
alternatives to insulin injections is the transplantation of insulin-secreting cells. It is the beta cells of the islets that secrete insulin
in response to increasing blood glucose concentrations. Ideally, transplantation of such cells (allografts or xenografts) could
restore normoglycemia. However, as with most tissue or cellular transplants, the cellular grafts, particularly xenografts, are
subjected to immunorejection in the absence of chronic immunosuppression. Thus, it is of great interest to develop new
technologies that may be used for islet cell replacement. This research proposal describes a new approach to cellular delivery
based on micro- and nanotechnology. Utilizing this approach, nanoporous biocapsules are bulk and surface micromachined to
present uniform and well-controlled pore sizes as small as 7 nm, tailored surface chemistries, and precise microarchitectures, in
order to provide immunoisolating microenvironments for cells. Such a design may overcome some of the limitations associated
with conventional encapsulation and delivery technologies, including chemical instabilities, material degradation or fracture,
and broad membrane pore sizes.
D 2004 Elsevier B.V. All rights reserved.
Keywords: Immunoisolation; Islet cells; Insulin; Biocapsule
1. Introduction
The immunoisolation of transplanted cells and
tissue by size-based semipermeable membranes has
emerged as an extremely promising method of treat-
ing hormone deficiencies arising from such diseases
as Type I diabetes, Alzheimer’s disease, and hemo-
philia [1 –6]. It has been demonstrated that cellular
transplants, such as isolated pancreatic islets of Lan-
gerhans or hepatocytes, respond physiologically both
in vitro and in vivo by secreting bioactive substances
in response to appropriate stimuli, as long as they are
immunoprotected. However, with the exception of
autologous cells and tissue, overcoming immunologic
rejection of the transplanted cells is still the greatest
obstacle [7,8]. Although approaches involving poly-
meric microcapsules have yielded promising results
for autologous and allogeneic cell transplantation
without immunosuppression [15–18], few approaches
have been effective for nonimmunosuppressed xeno-
0169-409X/$ - see front matter D 2004 Elsevier B.V. All rights reserved.
doi:10.1016.j.addr.2003.11.006
* Corresponding author. Tel.: +1-617-358-3054; fax: +1-617-
353-6776.
E-mail address: tdesai@bu.edu (T.A. Desai).
www.elsevier.com/locate/addr
Advanced Drug Delivery Reviews 56 (2004) 1661– 1673