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

Author

Listed:
  • Yonger Xue

    (The Ohio State University
    Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai)

  • Yuebao Zhang

    (The Ohio State University)

  • Yichen Zhong

    (The Ohio State University
    Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai)

  • 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
    The Ohio State University)

  • Darrell J. Irvine

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Ron Weiss

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Yizhou Dong

    (The Ohio State University
    Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai)

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.

Suggested Citation

  • 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 & R, 2024. "LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45094-5
    DOI: 10.1038/s41467-024-45094-5
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    References listed on IDEAS

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    1. Waracharee Srifa & Nina Kosaric & Alvaro Amorin & Othmane Jadi & Yujin Park & Sruthi Mantri & Joab Camarena & Geoffrey C. Gurtner & Matthew Porteus, 2020. "Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Geoffrey C. Gurtner & Sabine Werner & Yann Barrandon & Michael T. Longaker, 2008. "Wound repair and regeneration," Nature, Nature, vol. 453(7193), pages 314-321, May.
    3. Piotr Barć & Maciej Antkiewicz & Katarzyna Frączkowska-Sioma & Diana Kupczyńska & Paweł Lubieniecki & Wojciech Witkiewicz & Małgorzata Małodobra-Mazur & Dagmara Baczyńska & Dariusz Janczak & Jan Paweł, 2022. "Two-Stage Gene Therapy (VEGF, HGF and ANG1 Plasmids) as Adjunctive Therapy in the Treatment of Critical Lower Limb Ischemia in Diabetic Foot Syndrome," IJERPH, MDPI, vol. 19(19), pages 1-9, October.
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