{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T17:17:08Z","timestamp":1794503828279,"version":"4.9.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u00a0C-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.<\/jats:p>","DOI":"10.1038\/s41467-024-45094-5","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T07:09:39Z","timestamp":1706166579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-2487","authenticated-orcid":false,"given":"Yonger","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7883-1937","authenticated-orcid":false,"given":"Yuebao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xucheng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana D.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-9652","authenticated-orcid":false,"given":"David W.","family":"McComb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-1405","authenticated-orcid":false,"given":"Darrell J.","family":"Irvine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-2443","authenticated-orcid":false,"given":"Ron","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-0659","authenticated-orcid":false,"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"45094_CR1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nbt.2816","volume":"32","author":"JA Ankrum","year":"2014","unstructured":"Ankrum, J. A., Ong, J. F. & Karp, J. M. Mesenchymal stem cells: immune evasive, not immune privileged. Nat. Biotechnol. 32, 252\u2013260 (2014).","journal-title":"Nat. Biotechnol."},{"key":"45094_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s13287-020-01855-9","volume":"11","author":"X Wu","year":"2020","unstructured":"Wu, X. et al. Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress. Stem Cell Res. Ther. 11, 345 (2020).","journal-title":"Stem Cell Res. Ther."},{"key":"45094_CR3","doi-asserted-by":"publisher","first-page":"132501","DOI":"10.1088\/1361-6528\/ac4520","volume":"33","author":"Y Xue","year":"2022","unstructured":"Xue, Y., Baig, R. & Dong, Y. Recent advances of biomaterials in stem cell therapies. Nanotechnology 33, 132501 (2022).","journal-title":"Nanotechnology"},{"key":"45094_CR4","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1002\/cbf.1488","volume":"26","author":"Y Zhu","year":"2008","unstructured":"Zhu, Y. et al. Adipose\u2010derived stem cell: a better stem cell than BMSC. Cell Biochem. Funct. 26, 664\u2013675 (2008).","journal-title":"Cell Biochem. Funct."},{"key":"45094_CR5","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1091\/mbc.e02-02-0105","volume":"13","author":"PA Zuk","year":"2002","unstructured":"Zuk, P. A. et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279\u20134295 (2002).","journal-title":"Mol. Biol. Cell"},{"key":"45094_CR6","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/nri2395","volume":"8","author":"A Uccelli","year":"2008","unstructured":"Uccelli, A., Moretta, L. & Pistoia, V. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8, 726\u2013736 (2008).","journal-title":"Nat. Rev. Immunol."},{"key":"45094_CR7","first-page":"3499","volume":"110","author":"AJ Nauta","year":"2007","unstructured":"Nauta, A. J. & Fibbe, W. E. Immunomodulatory properties of mesenchymal stromal cells. Blood J. Am. Soc. Hematol. 110, 3499\u20133506 (2007).","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"45094_CR8","doi-asserted-by":"publisher","first-page":"108765","DOI":"10.1016\/j.biopha.2019.108765","volume":"114","author":"Z Si","year":"2019","unstructured":"Si, Z. et al. Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed. Pharmacother. 114, 108765 (2019).","journal-title":"Biomed. Pharmacother."},{"key":"45094_CR9","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.molmed.2010.02.005","volume":"16","author":"J Ankrum","year":"2010","unstructured":"Ankrum, J. & Karp, J. M. Mesenchymal stem cell therapy: Two steps forward, one step back. Trends Mol. Med. 16, 203\u2013209 (2010).","journal-title":"Trends Mol. Med."},{"key":"45094_CR10","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1161\/01.RES.0000265074.83288.09","volume":"100","author":"JM Gimble","year":"2007","unstructured":"Gimble, J. M., Katz, A. J. & Bunnell, B. A. Adipose-derived stem cells for regenerative medicine. Circ. Res. 100, 1249\u20131260 (2007).","journal-title":"Circ. Res."},{"key":"45094_CR11","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.108.176826","volume":"103","author":"M Gnecchi","year":"2008","unstructured":"Gnecchi, M., Zhang, Z., Ni, A. & Dzau, V. J. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res. 103, 1204\u20131219 (2008).","journal-title":"Circ. Res."},{"key":"45094_CR12","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41573-020-0064-x","volume":"19","author":"EA Kimbrel","year":"2020","unstructured":"Kimbrel, E. A. & Lanza, R. Next-generation stem cells \u2014 ushering in a new era of cell-based therapies. Nat. Rev. Drug Discov. 19, 463\u2013479 (2020).","journal-title":"Nat. Rev. Drug Discov."},{"key":"45094_CR13","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.stem.2012.02.005","volume":"10","author":"SH Ranganath","year":"2012","unstructured":"Ranganath, S. H., Levy, O., Inamdar, M. S. & Karp, J. M. Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease. Cell Stem Cell 10, 244\u2013258 (2012).","journal-title":"Cell Stem Cell"},{"key":"45094_CR14","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fcell.2020.00236","volume":"8","author":"S Ceccarelli","year":"2020","unstructured":"Ceccarelli, S., Pontecorvi, P., Anastasiadou, E., Napoli, C. & Marchese, C. Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application. Front. Cell Dev. Biol. 8, 236 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"45094_CR15","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.cmet.2015.09.019","volume":"22","author":"KS Ng","year":"2015","unstructured":"Ng, K. S., Kuncewicz, T. M. & Karp, J. M. Beyond Hit-and-Run: Stem Cells Leave a Lasting Memory. Cell Metab. 22, 541\u2013543 (2015).","journal-title":"Cell Metab."},{"key":"45094_CR16","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.3390\/jcm10132925","volume":"10","author":"M Sanchez-Diaz","year":"2021","unstructured":"Sanchez-Diaz, M. et al. Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review. J. Clin. Med 10, 2925 (2021).","journal-title":"J. Clin. Med"},{"key":"45094_CR17","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1002\/stem.1118","volume":"30","author":"L von Bahr","year":"2012","unstructured":"von Bahr, L. et al. Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation. Stem Cells 30, 1575\u20131578 (2012).","journal-title":"Stem Cells"},{"key":"45094_CR18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nrd.2016.245","volume":"16","author":"Y Shi","year":"2017","unstructured":"Shi, Y., Inoue, H., Wu, J. C. & Yamanaka, S. Induced pluripotent stem cell technology: a decade of progress. Nat. Rev. Drug Discov. 16, 115\u2013130 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"45094_CR19","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nrd4738","volume":"14","author":"EA Kimbrel","year":"2015","unstructured":"Kimbrel, E. A. & Lanza, R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat. Rev. Drug Discov. 14, 681\u2013692 (2015).","journal-title":"Nat. Rev. Drug Discov."},{"key":"45094_CR20","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.stem.2014.01.013","volume":"14","author":"M Mendicino","year":"2014","unstructured":"Mendicino, M., Bailey, A. M., Wonnacott, K., Puri, R. K. & Bauer, S. R. MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell 14, 141\u2013145 (2014).","journal-title":"Cell Stem Cell"},{"key":"45094_CR21","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","volume":"22","author":"J Galipeau","year":"2018","unstructured":"Galipeau, J. & Sens\u00e9b\u00e9, L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 22, 824\u2013833 (2018).","journal-title":"ell Stem Cell"},{"key":"45094_CR22","doi-asserted-by":"publisher","first-page":"eaba6884","DOI":"10.1126\/sciadv.aba6884","volume":"6","author":"O Levy","year":"2020","unstructured":"Levy, O. et al. Shattering barriers toward clinically meaningful MSC therapies. Sci. Adv. 6, eaba6884 (2020).","journal-title":"Sci. Adv."},{"key":"45094_CR23","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1038\/s41587-019-0137-8","volume":"37","author":"SR Bailey","year":"2019","unstructured":"Bailey, S. R. & Maus, M. V. Gene editing for immune cell therapies. Nat. Biotechnol. 37, 1425\u20131434 (2019).","journal-title":"Nat. Biotechnol."},{"key":"45094_CR24","doi-asserted-by":"publisher","first-page":"111236","DOI":"10.1016\/j.biopha.2021.111236","volume":"137","author":"Y Dong","year":"2021","unstructured":"Dong, Y. et al. Nanotechnology shaping stem cell therapy: Recent advances, application, challenges, and future outlook. Biomed. Pharmacotherapy 137, 111236 (2021).","journal-title":"Biomed. Pharmacotherapy"},{"key":"45094_CR25","doi-asserted-by":"publisher","first-page":"e23","DOI":"10.1182\/blood-2013-04-495119","volume":"122","author":"O Levy","year":"2013","unstructured":"Levy, O. et al. mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation. Blood 122, e23\u2013e32 (2013).","journal-title":"Blood"},{"key":"45094_CR26","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1039\/D1CS00786F","volume":"51","author":"Y Xue","year":"2022","unstructured":"Xue, Y. et al. Recent advances in biomaterial-boosted adoptive cell therapy. Chem. Soc. Rev. 51, 1766\u20131794 (2022).","journal-title":"Chem. Soc. Rev."},{"key":"45094_CR27","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1007\/s11684-011-0159-1","volume":"5","author":"C Wu","year":"2011","unstructured":"Wu, C. & Dunbar, C. E. Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity. Front. Med. 5, 356\u2013371 (2011).","journal-title":"Front. Med."},{"key":"45094_CR28","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","volume":"6","author":"X Hou","year":"2021","unstructured":"Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078\u20131094 (2021).","journal-title":"Nat. Rev. Mater."},{"key":"45094_CR29","doi-asserted-by":"publisher","first-page":"2000938","DOI":"10.1002\/adhm.202000938","volume":"10","author":"X Zhao","year":"2021","unstructured":"Zhao, X. et al. mRNA Delivery Using Bioreducible Lipidoid Nanoparticles Facilitates Neural Differentiation of Human Mesenchymal Stem Cells. Adv. Healthc. Mater. 10, 2000938 (2021).","journal-title":"Adv. Healthc. Mater."},{"key":"45094_CR30","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1021\/acs.nanolett.9b04246","volume":"20","author":"MM Billingsley","year":"2020","unstructured":"Billingsley, M. M. et al. Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering. Nano Lett. 20, 1578\u20131589 (2020).","journal-title":"Nano Lett."},{"key":"45094_CR31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s43586-023-00246-7","volume":"3","author":"S Chen","year":"2023","unstructured":"Chen, S. et al. Nanotechnology-based mRNA vaccines. Nat. Rev. Methods Prim. 3, 63 (2023).","journal-title":"Nat. Rev. Methods Prim."},{"key":"45094_CR32","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41578-021-00379-9","volume":"6","author":"C Horejs","year":"2021","unstructured":"Horejs, C. From lipids to lipid nanoparticles to mRNA vaccines. Nat. Rev. Mater. 6, 1075\u20131076 (2021).","journal-title":"Nat. Rev. Mater."},{"key":"45094_CR33","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/nature07039","volume":"453","author":"GC Gurtner","year":"2008","unstructured":"Gurtner, G. C., Werner, S., Barrandon, Y. & Longaker, M. T. Wound repair and regeneration. Nature 453, 314\u2013321 (2008).","journal-title":"Nature"},{"key":"45094_CR34","doi-asserted-by":"publisher","first-page":"265sr266","DOI":"10.1126\/scitranslmed.3009337","volume":"6","author":"SA Eming","year":"2014","unstructured":"Eming, S. A., Martin, P. & Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med 6, 265sr266 (2014).","journal-title":"Sci. Transl. Med"},{"key":"45094_CR35","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","volume":"376","author":"DG Armstrong","year":"2017","unstructured":"Armstrong, D. G., Boulton, A. J. & Bus, S. A. Diabetic foot ulcers and their recurrence. N. Engl. J. Med. 376, 2367\u20132375 (2017).","journal-title":"N. Engl. J. Med."},{"key":"45094_CR36","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nrendo.2015.130","volume":"11","author":"FL Bowling","year":"2015","unstructured":"Bowling, F. L., Rashid, S. T. & Boulton, A. J. Preventing and treating foot complications associated with diabetes mellitus. Nat. Rev. Endocrinol. 11, 606\u2013616 (2015).","journal-title":"Nat. Rev. Endocrinol."},{"key":"45094_CR37","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.dsx.2015.04.007","volume":"9","author":"S Noor","year":"2015","unstructured":"Noor, S., Zubair, M. & Ahmad, J. Diabetic foot ulcer\u2013A review on pathophysiology, classification and microbial etiology. Diabetes Metab. Syndr. 9, 192\u2013199 (2015).","journal-title":"Diabetes Metab. Syndr."},{"key":"45094_CR38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/bjs.4019","volume":"90","author":"SP Bennett","year":"2003","unstructured":"Bennett, S. P., Griffiths, G. D., Schor, A. M., Leese, G. P. & Schor, S. L. Growth factors in the treatment of diabetic foot ulcers. Br. J. Surg. 90, 133\u2013146 (2003).","journal-title":"Br. J. Surg."},{"key":"45094_CR39","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1046\/j.1524-475X.1999.00335.x","volume":"7","author":"JM Smiell","year":"1999","unstructured":"Smiell, J. M. et al. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen. 7, 335\u2013346 (1999).","journal-title":"Wound Repair Regen."},{"key":"45094_CR40","doi-asserted-by":"publisher","first-page":"eade7007","DOI":"10.1126\/sciadv.ade7007","volume":"9","author":"BR Freedman","year":"2023","unstructured":"Freedman, B. R. et al. Breakthrough treatments for accelerated wound healing. Sci. Adv. 9, eade7007 (2023).","journal-title":"Sci. Adv."},{"key":"45094_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16065-3","volume":"11","author":"W Srifa","year":"2020","unstructured":"Srifa, W. et al. Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice. Nat. Commun. 11, 2470 (2020).","journal-title":"Nat. Commun."},{"key":"45094_CR42","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.progpolymsci.2009.10.001","volume":"35","author":"F Fenouillot","year":"2010","unstructured":"Fenouillot, F., Rousseau, A., Colomines, G., Saint-Loup, R. & Pascault, J. P. Polymers from renewable 1,4:3,6-dianhydrohexitols (isosorbide, isomannide and isoidide): A review. Prog. Polym. Sci. 35, 578\u2013622 (2010).","journal-title":"Prog. Polym. Sci."},{"key":"45094_CR43","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/s41565-023-01453-9","volume":"18","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y. et al. Close the cancer\u2013immunity cycle by integrating lipid nanoparticle\u2013mRNA formulations and dendritic cell therapy. Nat. Nanotechnol. 18, 1364\u20131374 (2023).","journal-title":"Nat. Nanotechnol."},{"key":"45094_CR44","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1089\/hum.2017.121","volume":"28","author":"T Beissert","year":"2017","unstructured":"Beissert, T. et al. Improvement of In Vivo Expression of Genes Delivered by Self-Amplifying RNA Using Vaccinia Virus Immune Evasion Proteins. Hum. Gene Ther. 28, 1138\u20131146 (2017).","journal-title":"Hum. Gene Ther."},{"key":"45094_CR45","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jmb.2008.05.056","volume":"381","author":"PA Lemaire","year":"2008","unstructured":"Lemaire, P. A., Anderson, E., Lary, J. & Cole, J. L. Mechanism of PKR Activation by dsRNA. J. Mol. Biol. 381, 351\u2013360 (2008).","journal-title":"J. Mol. Biol."},{"key":"45094_CR46","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/s41580-021-00430-1","volume":"23","author":"YG Chen","year":"2022","unstructured":"Chen, Y. G. & Hur, S. Cellular origins of dsRNA, their recognition and consequences. Nat. Rev. Mol. Cell Biol. 23, 286\u2013301 (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"45094_CR47","doi-asserted-by":"publisher","first-page":"4133","DOI":"10.1039\/C5PY00521C","volume":"6","author":"A Wroblewska","year":"2015","unstructured":"Wroblewska, A. et al. Towards sugar-derived polyamides as environmentally friendly materials. Polym. Chem. 6, 4133\u20134143 (2015).","journal-title":"Polym. Chem."},{"key":"45094_CR48","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1002\/cssc.201100755","volume":"5","author":"F Aric\u00f2","year":"2012","unstructured":"Aric\u00f2, F., Tundo, P., Maranzana, A. & Tonachini, G. Synthesis of five-membered cyclic ethers by reaction of 1,4-diols with dimethyl carbonate. ChemSusChem 5, 1578\u20131586 (2012).","journal-title":"ChemSusChem"},{"key":"45094_CR49","doi-asserted-by":"publisher","first-page":"8099","DOI":"10.1021\/acs.nanolett.5b03528","volume":"15","author":"B Li","year":"2015","unstructured":"Li, B. et al. An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo. Nano Lett. 15, 8099\u20138107 (2015).","journal-title":"Nano Lett."},{"key":"45094_CR50","doi-asserted-by":"publisher","first-page":"8529","DOI":"10.1002\/anie.201203263","volume":"51","author":"M Jayaraman","year":"2012","unstructured":"Jayaraman, M. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int Ed. Engl. 51, 8529\u20138533 (2012).","journal-title":"Angew. Chem. Int Ed. Engl."},{"key":"45094_CR51","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1038\/s43018-020-0095-6","volume":"1","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat. Cancer 1, 882\u2013893 (2020).","journal-title":"Nat. Cancer"},{"key":"45094_CR52","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1111\/cts.12977","volume":"14","author":"JA Kessler","year":"2021","unstructured":"Kessler, J. A. et al. Gene therapy for diabetic peripheral neuropathy: A randomized, placebo-controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor. Clin. Transl. Sci. 14, 1176\u20131184 (2021).","journal-title":"Clin. Transl. Sci."},{"key":"45094_CR53","doi-asserted-by":"publisher","first-page":"12818","DOI":"10.3390\/ijerph191912818","volume":"19","author":"P Bar\u0107","year":"2022","unstructured":"Bar\u0107, P. et al. Two-Stage Gene Therapy (VEGF, HGF and ANG1 Plasmids) as Adjunctive Therapy in the Treatment of Critical Lower Limb Ischemia in Diabetic Foot Syndrome. Int. J. Environ. Res. Public Health 19, 12818 (2022).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"45094_CR54","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/j.1067-1927.2004.12404.x","volume":"12","author":"RD Galiano","year":"2004","unstructured":"Galiano, R. D. et al. Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen. 12, 485\u2013492 (2004).","journal-title":"Wound Repair Regen."},{"key":"45094_CR55","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/s41551-022-00905-2","volume":"6","author":"G Theocharidis","year":"2022","unstructured":"Theocharidis, G. et al. A strain-programmed patch for the healing of diabetic wounds. Nat. Biomed. Eng. 6, 1118\u20131133 (2022).","journal-title":"Nat. Biomed. Eng."},{"key":"45094_CR56","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41578-019-0148-6","volume":"5","author":"AC Daly","year":"2020","unstructured":"Daly, A. C., Riley, L., Segura, T. & Burdick, J. A. Hydrogel microparticles for biomedical applications. Nat. Rev. Mater. 5, 20\u201343 (2020).","journal-title":"Nat. Rev. Mater."},{"key":"45094_CR57","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1001\/archopthalmol.2011.1398","volume":"130","author":"L Espandar","year":"2012","unstructured":"Espandar, L. et al. Adipose-derived stem cells on hyaluronic acid\u2013derived scaffold: A new horizon in bioengineered cornea. Arch. Ophthalmol. 130, 202\u2013208 (2012).","journal-title":"Arch. Ophthalmol."},{"key":"45094_CR58","doi-asserted-by":"publisher","first-page":"3217","DOI":"10.3390\/ijms19103217","volume":"19","author":"A Ridiandries","year":"2018","unstructured":"Ridiandries, A., Tan, J. T. M. & Bursill, C. A. The Role of Chemokines in Wound Healing. Int. J. Mol. Sci. 19, 3217 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"45094_CR59","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1089\/wound.2014.0594","volume":"4","author":"RJ Bodnar","year":"2015","unstructured":"Bodnar, R. J. Chemokine regulation of angiogenesis during wound healing. Adv. Wound Care 4, 641\u2013650 (2015).","journal-title":"Adv. Wound Care"},{"key":"45094_CR60","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1073\/pnas.1716580115","volume":"115","author":"E V\u00e5gesj\u00f6","year":"2018","unstructured":"V\u00e5gesj\u00f6, E. et al. Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria. Proc. Natl Acad. Sci. 115, 1895\u20131900 (2018).","journal-title":"Proc. Natl Acad. Sci."},{"key":"45094_CR61","first-page":"392","volume":"69","author":"TE Restivo","year":"2010","unstructured":"Restivo, T. E., Mace, K. A., Harken, A. H. & Young, D. M. Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model. J. Trauma 69, 392\u2013398 (2010).","journal-title":"J. Trauma"},{"key":"45094_CR62","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ymeth.2008.03.006","volume":"45","author":"BA Bunnell","year":"2008","unstructured":"Bunnell, B. A., Flaat, M., Gagliardi, C., Patel, B. & Ripoll, C. Adipose-derived stem cells: Isolation, expansion and differentiation. Methods 45, 115\u2013120 (2008).","journal-title":"Methods"},{"key":"45094_CR63","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/stem.1878","volume":"33","author":"Z Wang","year":"2015","unstructured":"Wang, Z. et al. Engineered Mesenchymal Stem Cells with Enhanced Tropism and Paracrine Secretion of Cytokines and Growth Factors to Treat Traumatic Brain Injury. Stem Cells 33, 456\u2013467 (2015).","journal-title":"Stem Cells"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45094-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45094-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45094-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:06:35Z","timestamp":1783350395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45094-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,25]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["45094"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-45094-5","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,25]]},"assertion":[{"value":"7 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the initially published version of this article, incorrect data were inadvertently included in Source Data Fig. 5, Fig. S4, Fig. S6 and Fig. S12 during data transfer. Only the presentation of Fig. S6b is affected. The Source Data and figure have now been amended in the HTML and PDF versions of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Y.X., Y.Zhang., D.J.I., R.W., and Y.D. are inventors on a patent application (63\/433,109) filed by The Ohio State University and Massachusetts Institute of Technology. The patent covers engineered ASCs and their uses in this work. Y.D. is a scientific advisory board member and holds equity in Arbor Biotechnologies and Sirnagen Therapeutics. Y.D. is a co-founder and holds equity in Immunanoengineering Therapeutics. D.J.I. and R.W. are scientific advisory board members and hold equity in Strand Therapeutics. Other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"739"}}