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
N1 - Funding Information:
The authors would like to thank Dr. Mauro Ferrari of HMRI for helpful discussions on manuscript preparation and on the use of MSV. This work was financially supported by the NIH (5U54CA143837 and 1R21CA190024), the William Randolph Hearst Foundation, and the Cullen Trust for Health Care. In addition, J.O.M. was supported by the NIH predoctoral fellowships F31CA154119 and TL1RR024147. The authors would also like to thank Dr. Enrica De Rosa and HMRI Intravital Microscopy Core for IVM setup, acquisition, and analysis, Dr. David Haviland and HMRI Flow Cytometry Core Facility for flow cytometry setup and acquisition, Dr. Kemi Cui and HMRI Advanced Cellular and Tissue Microscope Core Facility for traditional confocal scanning services, HMRI Small Animal Imaging Core for access to IVIS Spectrum, HMRI Microscopy ‐ SEM/AFM Core for access to Nova NanoSEM 230, HMRI Research Pathology Core for tissue preparation, Dr. Junping You for animal manipulation, Dr. Bruna Corradetti for mouse MSC isolation and characterization, Dr. Jana S. Burchfield and Megan Livingston for constructive edits of this manuscript, and Dr. Erika L. Spaeth, Vivek Kuran, Sebastian Powell, Nupur Basu, Chibuike Ofoegbuna, Katy R. Lipscomb, Anna Pastò, and Christian Boada for assistance with various experiments including MSC maintenance, preparation of therapeutic components, assistance with animal experiments, and histology.
Funding Information:
The authors would like to thank Dr. Mauro Ferrari of HMRI for helpful discussions on manuscript preparation and on the use of MSV. This work was financially supported by the NIH (5U54CA143837 and 1R21CA190024), the William Randolph Hearst Foundation, and the Cullen Trust for Health Care. In addition, J.O.M. was supported by the NIH predoctoral fellowships F31CA154119 and TL1RR024147. The authors would also like to thank Dr. Enrica De Rosa and HMRI Intravital Microscopy Core for IVM setup, acquisition, and analysis, Dr. David Haviland and HMRI Flow Cytometry Core Facility for flow cytometry setup and acquisition, Dr. Kemi Cui and HMRI Advanced Cellular and Tissue Microscope Core Facility for traditional confocal scanning services, HMRI Small Animal Imaging Core for access to IVIS Spectrum, HMRI Microscopy - SEM/AFM Core for access to Nova NanoSEM 230, HMRI Research Pathology Core for tissue preparation, Dr. Junping You for animal manipulation, Dr. Bruna Corradetti for mouse MSC isolation and characterization, Dr. Jana S. Burchfield and Megan Livingston for constructive edits of this manuscript, and Dr. Erika L. Spaeth, Vivek Kuran, Sebastian Powell, Nupur Basu, Chibuike Ofoegbuna, Katy R. Lipscomb, Anna Past?, and Christian Boada for assistance with various experiments including MSC maintenance, preparation of therapeutic components, assistance with animal experiments, and histology.
Publisher Copyright:
© 2020 The Authors. Published by Wiley-VCH GmbH
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
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
UR - http://www.scopus.com/inward/record.url?scp=85092528783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092528783&partnerID=8YFLogxK
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 -