McMaster University

McMaster University

Technology

Fabrication

Encapsulation of cells

Cells are harvested and mixed thoroughly with alginate, a natural hexose polymer extracted from seaweeds. The cell-polymer mixture is extruded as beads into CaCl2 to cross-link the polymers, washed, and then laminated with poly-L-lysine and alginate to confer a coating with defined permeability property.


Polymer Chemistry

An important component of this technology is the polymers used for the microcapsule fabrication. They need to be biocompatible so as to be well-tolerated by the host, and once polymerized to form the microcapsules, they need to confer defined permeability so as to be an effective immune barrier, permit exchange of nutrients with waste, and allow exit of the therapeutic molecules. Most of the studies were performed using the natural hexose polymer alginate extracted from seaweeds. For improving the long-term integrity of the microcapsules, various strategies  such as incorporating covalent photopolymerization or auto-cross-linked polymers, and even using synthetic polymer (HHM) have been studied. An alginate visible with MRI, ferrofluid, has also been used to allow non-invasive monitoring of the implanted microcapsules.


Biology

Cell types used for microencapsulation

A second important component of this technology is the encapsulated cells. They have to grow well in the laboratory to permit genetic modification, to be robust to survive the encapsulation procedure, and to adapt well to the microenvironment within the implanted microcapsules. Although fibroblasts fulfill many of these requirements, the myoblasts are particularly suited as they can differentiate terminally and stop proliferating – thus permitting a longer term survival within the finite space of microcapsules.

Fibroblasts

Myoblasts : in microcapsules in vitro
: in microcapsules in vivo
: human fetal derivation

Molecular engineering

An important advantage of this technology is the versatility in creating “designer molecules” for delivery.  Thus,  therapeutic proteins have been engineered to permit secretion from within the microcapsules (secretary signal),  and  once secreted, to be able to home in to the desired cells (receptor targeting) or organs (brain targeting).

Brain targeting

While this microencapsulation technology permits the encapsulated cells to evade from the host’s immune response, the therapeutic molecules exiting from the microcapsules may present at times as foreign proteins, thus provoking an allergic reaction and negating the benefit of the therapy. Thus, various strategies were studied to suppress this type of immune response.

  • Imaging of implanted microcapsules

Once the microcapsules have been implanted in a host, their functional and physical status would be difficult to monitor. Hence, strategies were developed to permit follow-up without invasive surgery or microcapsule retrieval. These were accomplished by rendering the microcapsules visible to magnetic imaging (MRI) and the encapsulated cells visible to optical imaging (BLI).

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