Assessing the immunosuppressive activity of alginate-encapsulated mesenchymal stromal cells on splenocytes

Moise, Sandhya; Dolcetti, Luigi; Dazzi, Francesco; Roach, Paul; Buttery, Lee; MacNeil, Sheila; Medcalf, Nick

Abstract

Mesenchymal stromal cells (MSCs) show immunosuppressive effects both via cell-to-cell contact (direct) with immune cells and by producing paracrine factors and extracellular vesicles (indirect). A key challenge in delivering this therapeutic effect invivo is retaining the MSCs at the site of injection. One way to address this is by encapsulating the MSCs within suitable biomaterial scaffolds. Here, we assess the immunosuppressive effect of alginate-encapsulated murine MSCs on proliferating murine splenocytes. Our results show that MSCs are able to significantly suppress splenocyte proliferation by ∼50% via the indirect mechanism and almost completely (∼98%) via the direct mechanism. We also show for the first time that MSCs as monolayers on tissue culture plastic or encapsulated within alginate, when physically isolated from the splenocytes via transwells, are able to sustain immunosuppressive activity with repeated exposure to fresh splenocytes, for as long as 9 days. These results indicate the need to identify design strategies to simultaneously deliver both modes of MSC immunosuppression. By designing cell-biomaterial constructs with tailored degradation profiles, we can achieve a more sustained (avoiding MSCs migration and apoptosis) and controlled release of both the paracrine signals and eventually the cells themselves enabling efficient MSC-based immunosuppressive therapies for wound healing.

Citation

Moise, S., Dolcetti, L., Dazzi, F., Roach, P., Buttery, L., MacNeil, S., & Medcalf, N. (2022). Assessing the immunosuppressive activity of alginate-encapsulated mesenchymal stromal cells on splenocytes. Artificial Cells, Blood Substitutes and Biotechnology, 50(1), 168-176. https://doi.org/10.1080/21691401.2022.2088547

• Journal Article Type: Article
• Acceptance Date: Jun 5, 2022
• Online Publication Date: Jun 21, 2022
• Publication Date: Jun 21, 2022
• Deposit Date: May 2, 2025
• Publicly Available Date: May 2, 2025
• Journal: Artificial Cells, Nanomedicine, and Biotechnology
• Print ISSN: 1073-1199
• Electronic ISSN: 1532-4184
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 50
• Issue: 1
• Pages: 168-176
• DOI: https://doi.org/10.1080/21691401.2022.2088547
• Public URL: https://nottingham-repository.worktribe.com/output/38100620
• Publisher URL: https://www.tandfonline.com/toc/ianb20/50/1
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ianb20; Received: 2022-01-28; Accepted: 2022-06-05; Published: 2022-06-21