TY - JOUR
T1 - Mesenchymal Stromal Cell-Mediated Treatment of Local and Systemic Inflammation through the Triggering of an Anti-Inflammatory Response
AU - Martinez, Jonathan O.
AU - Evangelopoulos, Michael
AU - Brozovich, Ava A.
AU - Bauza, Guillermo
AU - Molinaro, Roberto
AU - Corbo, Claudia
AU - Liu, Xuewu
AU - Taraballi, Francesca
AU - Tasciotti, Ennio
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - drug delivery
KW - inflammation
KW - mesenchymal stromal/stem cells
KW - nanovectors
KW - sepsis
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U2 - 10.1002/adfm.202002997
DO - 10.1002/adfm.202002997
M3 - Article
AN - SCOPUS:85092528783
VL - 31
JO - Advanced Functional Materials
JF - Advanced Functional Materials
SN - 1616-301X
IS - 3
M1 - 2002997
ER -