Abstract
Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments. The PA nanofibers were able to create a mesh-like coating for a wide range of cell lineages with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The targeting abilities of this system were assessed in vitro using human primary regulatory T (hTreg) cells coated with PAs displaying a vascular cell adhesion protein 1 (VCAM-1) targeting motif. This approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies. Statement of significance: Cell therapies hold great promise in the treatment of diseases and tissue regeneration, but their clinical use has been limited by cell survival, targeting, and function. We report here a method to coat single cells with a biodegradable matrix of biomimetic nanofibers composed of peptide amphiphile (PA) molecules. The nanofibers were able to coat cells, such as human primary regulatory T cells, with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 50-61 |
| Number of pages | 12 |
| Journal | Acta Biomaterialia |
| Volume | 177 |
| DOIs | |
| State | Published - Mar 15 2024 |
Funding
This work was supported by an award from the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern and support from the NUGoKidney Program. Additional support was provided by the U.S. Army Medical Research and Materiel Command under award numbers W81XWH2110862 (Z.J.Z.) and W81XWH2110911 (J.M.). Biological and chemical analysis was performed in the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). Confocal imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Cryo-TEM work made use of the BioCryo facility of Northwestern University's NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. Flow cytometry analysis performed in this work was supported by the Northwestern University \u2013 Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). The authors thank Mark Seniw for 3D scientific illustration, Stacey Chin for assistance with cryo-TEM images, and Hiroaki Sai for assistance with SAXS measurements and analysis. This work was supported by an award from the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern and support from the NUGoKidney Program. Biological and chemical analysis was performed in the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute at Northwestern University . The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-1542205 ). Confocal imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Cryo-TEM work made use of the BioCryo facility of Northwestern University's NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-1542205 ); the MRSEC program ( NSF DMR-1720139 ) at the Materials Research Center; the International Institute for Nanotechnology (IIN) ; and the State of Illinois, through the IIN. Flow cytometry analysis performed in this work was supported by the Northwestern University \u2013 Flow Cytometry Core Facility supported by Cancer Center Support Grant ( NCI CA060553 ). The authors thank Mark Seniw for 3D scientific illustration, Stacey Chin for assistance with cryo-TEM images, and Hiroaki Sai for assistance with SAXS measurements and analysis.
Keywords
- Artificial extracellular matrices
- Peptide amphiphiles
- Regenerative medicine
- Regulatory T cells
- Single cell coating
- Supramolecular scaffolds
ASJC Scopus subject areas
- Biotechnology
- Biomaterials
- Biochemistry
- Biomedical Engineering
- Molecular Biology
