Understanding of Immunoisolation

A variety of systems can be employed for cell or enzyme immobilization. These include, for example, microcarriers, gel entrapment, hollow fibers, encapsulation and conformal coatings. The latter three have been extensively tested in small animal models over the last 20 years, particularly in the area of diabetes therapy. The polymeric materials used in bioartificial endocrine devices (the terms bioartificial and endocrine device are often distinguished from ‘artificial organs’ due to the presence of tissue in the former two) serve two major purposes:

1. As a scaffold and an extracellular matrix they favor the attachment and differentiation of functional cells or cell clusters and keep them separate from one another;

2. As permselective envelopes which provide immunoisolation of the transplant from the host.

The central concept of immunoisolation is the placement of a semipermeable barrier between the host and the transplanted tissue. The properties required for the semipermeable membranes used in cell transplantation depend strongly on the source of cells. An allograft is a transplant between individuals within one species, while a xenograft is a graft between individuals from different species.

Immunoisolation of transplanted cells by artificial barriers that permit crossover of low molecular weight substances, such as nutrients, electrolytes, oxygen, and bioactive secretory products, though not of immune cells and high molecular weight proteins such as antibodies (IgG, IgM), provides great promise for developing new technologies to overcome these problems in a reasonable time frame.

Device Geometry Considerations

The immunoisolation of allogeneic or xenogeneic islets can be achieved via two main classes of technology: macroencapsulation and microencapsulation. Macroencapsulation refers to the reliance on larger, prefabricated “envelopes” in which a slurry of islets or cell clusters is slowly introduced and sealed prior to implantation. An intravascular device usually consists of a tube through which blood flows, on the outside of which is the implanted tissue contained within a housing. The device is then implanted as a shunt in the cardiovascular system. Extravascular devices are implanted directly into tissue in a body space such as the peritoneal cavity, though some have also been vascularized into a major artery such as in Calafiore’s clinical trial. Geometrical alternatives include cylindrical tubular membranes containing tissue within the lumen and planar diffusion chambers comprised of parallel flat sheet membranes between which the implanted tissue is placed.

Microencapsulation refers to the formation of a spherical gel around each group of islets, cell cluster or tissue fragment. Microcapsules based on natural or synthetic polymers have been used for the encapsulation of both mammalian and microbial cells as well as various bioactive substances such as enzymes, proteins and drugs. A review of alternative semipermeable microcapsules prepared from oppositely charged water soluble polyelectrolyte pairs has been presented in recent papers. The main advantage of this approach is that cells, or bioactive agents, are isolated from the body by a microporous semipermeable membrane and the encapsulated material is thus protected against the attack of the immune system. In the case of microencapsulated pancreas islets, a suspension of microcapsules is typically introduced in the peritoneal cavity to deliver insulin to the portal circulation.

Tags: Bio Technology, Bio Genetics, Cell Encapsulation

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