2. Academic Validation
  3. LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing

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

  • Nat Commun. 2024 Jan 25;15(1):739. doi: 10.1038/s41467-024-45094-5.
Yonger Xue # 1 2,  Yuebao Zhang # 1,  Yichen Zhong # 1 2,  Shi Du 1,  Xucheng Hou 2,  Wenqing Li 1,  Haoyuan Li 2,  Siyu Wang 2,  Chang Wang 2,  Jingyue Yan 1,  Diana D Kang 1,  Binbin Deng 3,  David W McComb 3 4,  Darrell J Irvine 5 6 7 8 9,  Ron Weiss 5 10 11,  Yizhou Dong 12 13
Affiliations

Affiliations

  • 1 Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
  • 2 Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 3 Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA.
  • 4 Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, USA.
  • 5 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 6 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 7 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 8 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • 9 Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • 10 Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • 11 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • 12 Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA. yizhou.dong@mssm.edu.
  • 13 Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yizhou.dong@mssm.edu.
  • # Contributed equally.
PMID: 38272900 DOI: 10.1038/s41467-024-45094-5
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.

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