LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing

Yonger Xue, Yuebao Zhang, Yichen Zhong, Shi Du, Xucheng Hou, Wenqing Li, Haoyuan Li, Siyu Wang, Chang Wang, Jingyue Yan, Diana D. Kang, Binbin Deng, David W. McComb, Darrell J. Irvine, Ron Weiss and Yizhou Dong ()
Additional contact information
Yonger Xue: The Ohio State University
Yuebao Zhang: The Ohio State University
Yichen Zhong: The Ohio State University
Shi Du: The Ohio State University
Xucheng Hou: Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai
Wenqing Li: The Ohio State University
Haoyuan Li: Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai
Siyu Wang: Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai
Chang Wang: Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai
Jingyue Yan: The Ohio State University
Diana D. Kang: The Ohio State University
Binbin Deng: The Ohio State University
David W. McComb: The Ohio State University
Darrell J. Irvine: Massachusetts Institute of Technology
Ron Weiss: Massachusetts Institute of Technology
Yizhou Dong: The Ohio State University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.

Date: 2024
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DOI: 10.1038/s41467-024-45094-5

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