Mesenchymal Stromal Cell-Mediated Treatment of Local and Systemic Inflammation through the Triggering of an Anti-Inflammatory Response

Jonathan O. Martinez, Michael Evangelopoulos, Ava A. Brozovich, Guillermo Bauza, Roberto Molinaro, Claudia Corbo, Xuewu Liu, Francesca Taraballi, Ennio Tasciotti

Research output: Contribution to journalArticle

Abstract

The emergence of cell-based therapeutics, specifically the use of mesenchymal stromal/stem cells (MSCs), stands to significantly affect the future of targeted drug delivery technologies. MSCs represent a unique cell type, offering more than only regenerative potential but also site-specific inflammatory targeting and tissue infiltration. In this study, a versatile multicomponent delivery platform, combining MSC tropism with multistage nanovector (MSV)-mediated payload delivery, is debuted. It is demonstrated that the incorporation of drug-loaded MSVs bestows MSCs with the ability to transport anti-inflammatory payloads, achieving a fivefold increase in payload release without negatively impacting cellular functions, viability, extravasation, and inflammatory homing. When incorporated within MSCs, MSVs avoid rapid sequestration by filtering organs and conserve a 15-fold increase in local inflammatory targeting compared to healthy ears. Furthermore, this MSC-mediated MSV platform (M&Ms) rapidly triggers a 4.5-fold reduction of local inflammation compared to free drug and extends survival to 100% of treated mice in a lethal model of systemic inflammation.

Original languageEnglish (US)
Article number2002997
JournalAdvanced Functional Materials
Volume31
Issue number3
DOIs
StateAccepted/In press - 2020

Keywords

  • drug delivery
  • inflammation
  • mesenchymal stromal/stem cells
  • nanovectors
  • sepsis

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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