Nature Chemistry | The Sceptical Chymist

2011 Fall MRS: A plug for stem cells

Posted on behalf of Rosamund Daw (Senior Editor, Nature)

In the field of materials science as applied to regenerative medicine, a common theme is the design of novel scaffold materials as supports for stem cell growth and differentiation. However not all stem cell therapies use scaffolds. In some biomedical research efforts, cells are injected directly into the site of need. Such a strategy has been applied to a variety of different injuries and diseases, for example Parkinson’s disease, stroke, heart attack and spinal-cord injuries. Though the approach has had some successes, a major stumbling block has been simply the ability to deliver a payload of viable cells to the site. Sarah Heilshorn at Stanford University has been investigating how materials science can help and presented her group’s findings in the ‘Biomaterials for Tissue Regeneration’ Symposium at the Fall MRS [The design of hydrogel cell carriers to improve stem cell viability during transplantation by direct injection; Brian Aguado, Sarah Heilshorn; Symposium KK; 2011 MRS Fall Meeting].

Early in vitro model experiments surprisingly revealed that the cell injection procedure itself led to severe membrane damage and around 40% cell death. Heilshorn suggested that this cell death was the result of elongational flow at the entrance of the syringe needle, disrupting cell membranes. Her research group has been investigating how hydrogels can mechanically protect cells from damage during injection. In particular they have focused on physically-crosslinked protein hydrogels. The physical crosslinks are easily broken on the application of shear, and it is this which Heilshorn believes helps protect the cells. The hydrogel shear thins at the walls of the syringe during injection providing lubrication to allow the rest of the gel to flow as a plug through the needle rather than with the differential flows across the bore experienced by a fluid which causes the extensive cell death.

Ingeniously, the material is comprised of two components and gelation occurs on mixing. This obviates the need for one of the usual gelation ‘triggers’ such as a temperature or pH, required in a single component gel, which can also damage the cells.

Heilshorn’s group have demonstrated that human adipocyte-derived stem cells and mouse adipocyte-derived stem cells can happily proliferate and differentiate inside the hydrogels. Furthermore the hydrogels improve the retention of cells injected into a mouse model, compared to delivery in alginate, saline or collagen. Adipocyte- or fat-derived stem cells are easily harvested from patients and are likely to be one of the first stem cell types to be used routinely in the clinic.

I shall look forward to the next chapter in the story, to find out if the hydrogels offer enhanced therapeutic capability.


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