Translating Stem Cells From Laboratory to Clinic - Ontario-area scientists discuss approaches to development of stem-cell therapies. - BioPharm International

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Translating Stem Cells From Laboratory to Clinic
Ontario-area scientists discuss approaches to development of stem-cell therapies.


BioPharm International
Volume 26, Issue 4, pp. 40-45

DELIVERY SYSTEMS


Molly Soichet
Molly Soichet, PhD, professor, Chemical Engineering and Applied Chemistry, Canada Research Chair in Tissue Engineering, University of Toronto.

BioPharm: Developing stem cells as therapeutics will require specialized methods to deliver cells to specific sites within the body, with the goal either to allow those cells to integrate into host tissues or to remain encapsulated as drug delivery vehicles. Can you discuss the role that materials science plays in developing cell therapy delivery systems?

Soichet: There are three strategies that have required materials science for cell therapy. In encapsulated cell therapy, cells are encased in a polymeric membrane that allows the selective diffusion of biomolecules across the membrane. The idea is that the cells act as growth factor factories, producing biologically-active molecules on demand, as in the case of diabetes, or constitutively, in the case of Parkinson's Disease. The proteins produced by the cells can diffuse out of the membrane and nutrients and oxygen can diffuse into the membrane, keeping the cells encased within the membrane viable and functional. The goal of encapsulated cell therapy is that the polymeric membrane provides stealth properties to the cells within, so that they are not rejected. This method works, but there continues to be challenges with transplanting sufficient numbers of cells to have a therapeutic effect and to have this effect sustained for a sufficiently long time. Immunogenic factors are thought to be too large to diffuse in; however, when encapsulated cells die, they may shed some antigens that lead to an inflammatory response.

In exogenous cell delivery, cells are often transplanted in saline or a minimal medium; however, most of the cells die upon transplantation. In the nervous system, the goal is for the transplanted cells to survive and integrate into the host circuitry. To achieve these two big challenges in the field, the polymeric biomaterial serves to provide a permissive environment for enhanced survival and cell integration. Unlike encapsulated cell therapy, in exogenous cell delivery the goal is to have the transplanted cells migrate out of the biomaterial and integrate with the host. By enhancing cell survival (through the choice and design of the biomaterial), cell integration becomes more likely, leading to greater tissue regeneration and functional recovery.

In endogenous cell stimulation, the resident stem cells are stimulated through the delivery of biomolecules that promote their proliferation, migration, and differentiation. Here again, biomaterials can be used to deliver those factors that are required. Using injectable polymers and controlled-release vehicles, minimally invasive strategies can be developed.


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