The autoimmune response in type 1 diabetes combined with the response to allogeneic cell transplantation remains a formidable barrier to transplant success that currently requires the use of powerful immunosuppressive drugs.
Encapsulation strategies have the potential to ameliorate these responses to promote survival post-transplantation, with modifications to the biomaterial chemistry, the incorporation of biologics or cell co-transplantation being used to avoid lifelong immunosuppression.
Allogeneic islets are the current standard for clinical use; however, the supply of these islets is insufficient to meet the need for patients. Alternative sources such as human embryonic stem cell-derived β-cells and porcine islets have the potential to satisfy demand, although efficacy, safety and regulatory issues remain to be addressed.
Vascularization of the transplant site is being developed to enhance islet function post-transplantation by providing the nutrients necessary for survival, while also allowing the sensing of glucose and the distribution of insulin. Oxygen is frequently the limiting factor and oxygen delivery systems are also being developed to complement the vascularization process.
A small number of islet encapsulation systems have been applied clinically, all of which have demonstrated good safety profiles, although it is too early to evaluate functional outcomes.
Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans.
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Financial support for this work was provided by R01EB009910 (L.D.S.) and JDRF (T.D. and L.D.S.).
L.D.S. has financial interests in Cour Pharmaceuticals Development Co. T.D. is a scientific founder of Encellin Inc., a cell therapy device company. The University of California, San Francisco (UCSF) has filed a provisional patent application on a macroencapsulation technology for cell-based therapy.
- Type 1 diabetes
(T1D). A chronic condition of aberrant glucose homeostasis that is characterized by a severe deficiency of insulin secretion resulting from atrophy of the islets of Langerhans.
Insulin-secreting cells of the islets of Langerhans.
Elevated blood glucose above normal levels.
Suppressed blood glucose below normal levels.
Suppression (such as, by drugs or disease) of the immune response.
Derived from, originating in or being a member of another species.
To surround, encase or protect in or as if in a capsule.
The presence of a normal concentration of glucose in the blood.
The formation of blood vessels.
Involving, derived from, or being genetically identical or similar individuals of the same species, especially with respect to antigenic interaction.
Involving, derived from or being individuals of the same species that are sufficiently genetically dissimilar to interact antigenically.
A condition marked by an increase in interstitial fibrous or scar tissue.
The ability of a particular substance to provoke an immune response in the body of a human or an animal.
A deficiency of oxygen reaching the tissues of the body.
The failure to mount an immune response to a person's own proteins and other antigens.
Members of a class of immunoregulatory proteins (interleukin or interferon) that are secreted by cells especially of the immune system.
- Regulatory T cells
(Treg cells). A subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens and prevent autoimmune disease.
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