MICROBEADS

MICROBEADS

A key component for developing successful retinal degeneration drug treatments is the availability of efficient drug delivery systems. A variety of systems under active development include virus vectors, cell-based delivery vehicles and encapsulated devices. However, new research led by Dr M Dominik Fischer, now at the Nuffield Laboratory of Ophthalmology, Oxford, introduces a novel approach, which he presented to delegates attending the 3rd EURETINA Winter Meeting. The new system, characterised by the delivery of genetically engineered human mesenchymal stem cells (MSCs) encapsulated within miniaturised alginate spheres or “MicroBeads”, may provide the means to achieve sustained drug release without necessitating repeat administration.

Dr Fischer explained that MicroBeads were “small spherical structures with a core of human mesenchymal stem cells, the core, about 120 μm across in diameter is protected by a biopolymer that shields the cells from the host humoral and cellular immune response but is semi-permeable for small proteins or substances, and biologicals that can be secreted with a size limit of about 300kDa. So it is quite a versatile system in that you can engineer those cells to secrete neuro-protective substances or even antiangiogenic or anti-inflammatory biologicals”.

The concept of MicroBeads,
Courtesy of M Dominik Fischer

Such a delivery system may provide an advantage over alternative approaches if the engineered cells can be designed to deliver a steady and reproducible level of therapeutic biologicals over a sustained period of time.

Dr Fischer told delegates that for “any form of retinal disorder you would think that there is a therapeutic target level of your biological that you would like to achieve; if you do an intravitreal injection you have a quick rise of concentration of your drug and a quick drop again; ideally you would like to achieve consistent dosing at that therapeutic target level and have a physiological feedback between the diseased tissue and your compound. This is why we think MircoBeads might be a good idea; having a cellular system in place that can have a physiological feedback with the target tissue and possibly express the therapeutic biological around the ideal target level”.

The initial objective of Dr Fischer’s studies at the Centre for Ophthalmology in Tubingen was to monitor the viability of MicroBead encapsulated MSCs in the mouse eye by histologically tracking the impact of the delivery procedure and the subsequent expression of an engineered reporter construct, green fluorescent protein.

Dr Fischer reported that successful expression of the reporter gene was demonstrated for up to four months following implantation. In addition, the research results showed that the MicroBeads remained stationary and functional throughout the four months investigated suggesting the potential of MicroBeads for sustained delivery of biologicals making them a promising candidate for intermediate-term therapeutic use in human hereditary retinal degenerations and other ocular disorders.

While there may be significant further work ahead in optimising the technology, the opportunity to control levels of therapeutic drug delivery will undoubtedly spur continued research on the application of the encapsulated cells. In particular, the use of inducible promoters to control gene expression and thereby ensure constant and safe therapeutic levels of a drug, combined with the added safety feature of a cellular suicide gene, all present a level of control for clinicians to fine tune the next wave of molecular medicine tools. 

 

 

 

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