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Journal article
Macrophage cell therapy enabled by interleukin-4 mRNA-loaded lipid nanoparticles to sustain a pro-reparative phenotype in inflammatory injuries
Biomaterials, v 328, 123869
May 2026
PMID: 41317703
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Abstract
The use of macrophage cell therapies is limited by their tendency to change phenotype in response to external cues in situ. Here we demonstrate that an optimized lipid nanoparticle (LNP) formulation effectively delivers IL4 mRNA to human and murine primary macrophages, resulting in rapid transfection, IL-4 secretion, and reparative phenotype modulation. In a model of murine volumetric muscle loss, adoptively transferred macrophages pre-treated with IL4-LNPs maintained a reparative phenotype for at least one week, despite the inflammatory injury microenvironment. IL4-LNP-treated macrophages also promoted a reparative phenotype in endogenous macrophages and supported muscle repair outcomes, including increased vascularization, fiber size distribution, and remodeling of the scaffold. T cell subtype in the muscle or the draining lymph node was not affected. The novel strategy established here may facilitate the control and use of macrophage cell therapies for other applications in regenerative medicine.
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Details
- Title
- Macrophage cell therapy enabled by interleukin-4 mRNA-loaded lipid nanoparticles to sustain a pro-reparative phenotype in inflammatory injuries
- Creators
- Erin M. O'Brien - Drexel UniversityTina Tylek - Drexel UniversityHannah C. Geisler - University of PennsylvaniaAlvin J. Mukalel - University of PennsylvaniaRicardo C. Whitaker - Drexel UniversitySamuel Sung - Drexel UniversityBenjamin I. Binder-Markey - Drexel UniversityDrew Weissman - University of PennsylvaniaMichael J. Mitchell - University of PennsylvaniaKara L. Spiller (Corresponding Author) - Drexel University
- Publication Details
- Biomaterials, v 328, 123869
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- US National Institutes of Health: NHLBI HL130037, NIAMS AR083080, NHLBI HL158189 NIH Director's New Innovator Award: DP2 TR002776 Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI)US National Science Foundation CAREER Award: CBET-2145491 Congressionally Directed Medical Research Programs (CDMRP): PR201467 NCI: 5P30CA056036-17
This work was supported by the US National Institutes of Health, NHLBI HL130037 to KLS, NIAMS AR083080 to KLS, and NHLBI HL158189 to EMO. MJM acknowledges support from an NIH Director's New Innovator Award (DP2 TR002776), a Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI), a US National Science Foundation CAREER Award (CBET-2145491), and the Congressionally Directed Medical Research Programs (CDMRP) (PR201467). This work utilized the Translational Pathology Shared Resource, as well as the Flow Cytometry and Human Immune Monitoring Shared Resource at the Sidney Kimmel Cancer Center, supported by the NCI grant 5P30CA056036-17. Some flow cytometry experiments were conducted at Drexel University's Cell Imaging Center, RRID:SCR_022689. The authors are grateful to Anisha Pavani and Jacob Taub for technical assistance.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Chemical and Biological Engineering; Physical Therapy (and Rehabilitation Sciences)
- Web of Science ID
- WOS:001631872400001
- Scopus ID
- 2-s2.0-105026628155
- Other Identifier
- 991022133488604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials