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

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...

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Bibliographic Details
Published in:Nature communications 2024-01, Vol.15 (1), p.739-13, Article 739
Main Authors: Xue, Yonger, Zhang, Yuebao, Zhong, Yichen, Du, Shi, Hou, Xucheng, Li, Wenqing, Li, Haoyuan, Wang, Siyu, Wang, Chang, Yan, Jingyue, Kang, Diana D., Deng, Binbin, McComb, David W., Irvine, Darrell J., Weiss, Ron, Dong, Yizhou
Format: Article
Language:English
Subjects:
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Chemokines
CXCL12 protein
Diabetes
Diabetes mellitus
Effectiveness
Growth factors
Hepatocyte growth factor
Humanities and Social Sciences
Immune response
Lipids
mRNA
multidisciplinary
Nanoparticles
Pharmacology
Proteins
Regeneration (physiology)
Science
Science (multidisciplinary)
Stem cells
Tissue engineering
Wound healing
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Summary: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. Adipose stem cells are promising therapeutic agents in tissue regeneration. Here the authors develop a lipid nanoparticle/RNA engineering platform to enhance the protein production of these cells, which demonstrate superior healing efficacy in a mouse model of diabetic cutaneous wounds.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45094-5