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Single-Cell Encapsulation for Improved Cell Therapies

Tunable crosslinked alginate microgels that improve persistence and function of mesenchymal stromal cells

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This three-dimensional rendering shows the nucleus (greenish blue) and cytoskeleton (yellow) of a single encapsulated mesenchymal stromal cell (MSC) surrounded by a thin layer of alginate hydrogel (purple). This microfluidic-enabled method for encapsulating single cells could pave the way for more effective cell therapies and precise tissue engineering capabilities. Credit: Wyss Institute at Harvard University

Mesenchymal stromal cells (MSCs) are valued for their ability to secrete compounds that modulate the body’s immune system, making them an attractive solution for existing problems with cell therapies including host-vs-graft disease and organ transplant rejections. However, MSCs are rapidly cleared from the body and can come under fire from the immune system. Efforts to address these issues by suspending MSCs in protective biomaterials have resulted in bulky hydrogels that are too large to be given intravenously and can stifle the MSCs’ function.

The Wyss Institute has developed a novel single-cell encapsulation method that coats individual MSCs with a thin layer of an alginate-based hydrogel that is thin enough to be termed a “microgel.” The microgel is further cross-linked for improved resistance to mechanical clearance and immune attack, and is cultured so that the MSCs within it multiply to produce a greater collective effect. These tunable microgels provide the protective value of a biomaterial coating, allow injectability, and enhance cell functionality.

One of the strong points of this work is that it uses a completely non-genetic approach to dramatically increase cell survival in transplant contexts, where it’s sorely needed.

David Mooney
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Dividing MSCs (blue) within a thin layer of the crosslinked alginate microgel (purple) showed improved performance over a previous version of the microgel, and could be a model for improving cell therapy in humans. Credit: Wyss Institute at Harvard University

Initial experiments in mice demonstrated that these cross-linked, multicellular microgels dramatically extended the persistence of MSCs in the body, even when an immune response against the microgel was induced. When introduced into mice along with allogeneic bone marrow cells, the encapsulated MSCs led to a greater number of allogeneic marrow cells in the mice’s marrow cavity and blood and increased the amount of allogeneic marrow engraftment compared to bare MSCs.

Importantly, these encapsulates can be readily preserved by cryofreezing, making them amenable to use in hospitals and other clinical centers.

This technology is undergoing further de-risking at the Wyss Institute.

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