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

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

Research output: Contribution to journalArticlepeer-review

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 in vivo 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.
Original languageEnglish
Pages (from-to)168-176
Number of pages9
JournalArtificial Cells, Nanomedicine, and Biotechnology
Volume50
Issue number1
Early online date22 Jun 2022
DOIs
Publication statusPublished - 31 Dec 2022

Keywords

  • Mesenchymal stromal cells
  • alginate
  • encapsulation
  • immunosuppression
  • splenocytes

ASJC Scopus subject areas

  • Biotechnology
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmaceutical Science

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