History, challenges and perspectives of cell microencapsulation

doi:10.1016/j.tibtech.2003.11.004

Trends in Biotechnology

Volume 22, Issue 2, February 2004, Pages 87-92

https://doi.org/10.1016/j.tibtech.2003.11.004 Get rights and content

Abstract

Cell microencapsulation continues to hold significant promise for biotechnology and medicine. The controlled, and continuous, delivery of therapeutic products to the host by immunoisolated cells is a potentially cost-effective method to treat a wide range of diseases. Although there are several issues that need to be addressed, including capsule manufacture, properties and performance, in the past few years, a stepwise analysis on the essential obstacles and limitations has brought the whole technology closer to a realistic proposal for clinical application. This paper summarizes the current situation in the cell encapsulation field and discusses the main events that have occurred along the way.

Section snippets

Potential advantages

In light of the increasing incidence of age-related diseases and the current desperate shortage of donor organs, the hope that encapsulated cells might be used as a therapeutic tool is increasingly being 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

Materials

It is widely understood that biocompatible materials, which do not interfere with cell homeostasis, have to be applied within capsules to allow for survival of the enclosed cells, and that the polymers used for allo- and xenotransplantation will differ, with the latter process probably requiring a much tighter membrane. Furthermore, it is essential that the capsules should have an adequate mechanical stability to allow for exchange of nutrients and metabolic waste.

In the search for a better

Diffusion and mass transport

The premise in designing a device with a semipermeable membrane is to adjust its permeability, in terms of the entry and exit of molecules. The appropriateness of a membrane depends on the control it allows over both the size-based exclusion and rate of diffusion of the molecules which either should or should not permeate the membrane to control the survival, as well as the metabolic efficacy, of the graft. Generally, the process of transporting various species across a membrane, characterized

Microcapsule mechanical stability

The initial enthusiasm regarding the alginate-PLL microcapsule was dampened after realizing that the membrane exhibits poor mechanical stability. The additional efforts in achieving the improved mechanical stability and durability of capsules resulted in a modification to the chemical composition of the membrane (Table 1). One approach involved replacing PLL with poly-L-ornithine (PLO) and decreasing capsule size from 800 to 400 μm [25]. In another study, polyanions with both weak (alginate)

Rejection pathways

Several pathways are involved in the rejection of immunoisolated cells. In allograft immunity, because immune mechanisms mainly consist of direct engagement of T lymphocyte sub-populations (i.e. CD8⁺) with donor cells, the physical isolation provided by the capsules should prevent cell-to-cell contact between the encapsulated tissue and the host's immune system, thereby facilitating the immunological acceptance of the graft. In the case of xenograft immunity, microcapsules could prevent access

Cell lines

Judicious choice of encapsulated cells is essential for the success of any biomedical application. Over the past few years, many different cell sources have been immobilized (immunoisolation is a specific form of a more general term – immobilization – with the former referring only to transplantation) (Figure 1), although clearly not all cells are suitable for encapsulation. Several factors should be carefully considered when choosing appropriate cell types for immobilization. The use of

Applications

The economic costs for standard medical treatment have contributed to the re-evaluation of the affordability of public and private healthcare options in many countries. In the USA alone, hundreds of billion dollars, ∼10% of the Gross National Product, are spent on the treatment of neurodegenerative and endocrine diseases and inborn errors of metabolism, as well as a variety of acute and chronic organ failures. Eighty five percent of these expenses are a result of the morbidity associated with

Future perspectives

Microencapsulation has a potentially significant future in medicine and biotechnology, the latter including agricultural and environmental applications. However, several significant challenges still face cell microencapsulation technology. For example, dosing should be carefully controlled by using cells that thrive and proliferate to a limited degree only, thereby preventing uncontrolled cell growth and overcrowding of the cells within the immunoisolation device. Moreover, constituent polymers

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Trends in Biotechnology

History, challenges and perspectives of cell microencapsulation

Abstract

Section snippets

Potential advantages

Materials

Diffusion and mass transport

Microcapsule mechanical stability

Rejection pathways

Cell lines

Applications

Future perspectives

Blood

Lancet

Lancet

Biomaterials

Biomaterials

Adv. Drug Deliv. Rev.

Int. J. Pharm.

Biomaterials

Adv. Drug Deliv. Rev.

Trends Mol. Med.

Lancet

Uber die antineoplastische immunitat; heterologe Einpflnzung von Tumoren in Huhner-embryonen

Ztschr. Krebsforsch

Semipermeable microcapsules

Science

Beta cell culture on synthetic capillaries: an artificial endocrine pancreas

Science

Microencapsulated islets as bioartificial endocrine pancreas

Science

Microencapsulated genetically engineered live E. coli DH5 cells administered orally to maintain normal plasma urea level in uremic rats

Nat. Med.

Normalization of diabetes in spontaneously diabetic cynomologous monkeys by xenografts of microencapsulated porcine islets without immunosuppression

J. Clin. Invest.

Cell encapsulation: promise and progress

Nat. Med.

Encapsulated cell technology

Nat. Biotechnol.

Islet transplantation in seven patients with Type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen

N. Engl. J. Med.

Human therapeutic cloning

Nat. Med.

Improvement of the biocompatibility of alginate/poly-L-lysine/alginate microcapsules by the use of epimerized alginate as a coating

J. Biomed. Mater. Res.