{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:09:26Z","timestamp":1790107766266,"version":"4.0.1"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270701"],"award-info":[{"award-number":["82270701"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project of Chinese Hospital Reform and Development Institute, Nanjing University","award":["NDYGN2023003"],"award-info":[{"award-number":["NDYGN2023003"]}]},{"name":"Project of Chinese Hospital Reform and Development Institute, Nanjing University","award":["NDYGN2023036"],"award-info":[{"award-number":["NDYGN2023036"]}]},{"name":"Clinical Research Special Fund of Nanjing Drum Tower Hospital","award":["2024-LCYJ-PY-77"],"award-info":[{"award-number":["2024-LCYJ-PY-77"]}],"id":[{"id":"https:\/\/ror.org\/026axqv54","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nanjing Municipal Health Science and Technology Development Special Fund Project","award":["YKK23089"],"award-info":[{"award-number":["YKK23089"]}]},{"name":"Nanjing Municipal Health Science and Technology Development Special Fund Project","award":["YKK23108"],"award-info":[{"award-number":["YKK23108"]}]},{"name":"Natural Science Foundation of Jiangsu Province of China","award":["BK20230141"],"award-info":[{"award-number":["BK20230141"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genetic engineering of therapeutic cells is a key strategy to enhance cell-based therapies, yet current gene delivery methods\u2014viral vectors, electroporation, and commercial non-viral reagents\u2014are limited by safety concerns, high cost, operational complexity, cytotoxicity, and poor scalability. We developed a safe, efficient, low-cost, and scalable non-viral gene delivery platform using a polyethylene glycol-polyethyleneimine (PEG-PEI) copolymer to engineer mesenchymal stromal cells (MSCs) for inflammatory bowel disease (IBD) treatment. The PEG-PEI copolymer was synthesized via covalent conjugation and formed stable core\u2212shell nanocomplexes (\u223c130 nm, +20 mV) that completely protected DNA at N\/P \u2265 10. In primary human MSCs, this platform achieved 43.8% EGFP-positive MSCs and enhanced IL-10 and bFGF secretion by approximately 2-fold and 1.6-fold, respectively, compared to Lipofectamine 3000, without compromising cell viability or multipotency. Engineered IL-10-overexpressing MSCs (PEG-PEI-IL-10-MSCs) were constructed and evaluated in a dextran sulfate sodium-induced murine acute colitis model. PEG-PEI-IL-10-MSCs restored body weight, reduced disease activity, ameliorated colon shortening and histopathological damage with efficacy comparable to the first-line drug 5-ASA, and significantly outperformed conventionally engineered or unmodified MSCs. Mechanistically, the treatment promoted epithelial proliferation and goblet cell regeneration, drove macrophage polarization toward an M2-reparative phenotype, suppressed pro-inflammatory cytokines (TNF-\u03b1 and IL-6), and selectively normalized pathological angiogenesis while preserving functional vasculature. This PEG-PEI platform effectively overcomes the critical bottleneck of difficult-to-transfect primary MSCs, providing a versatile tool for cell engineering and a foundation for next-generation synergistic cell-and-gene therapies for IBD.<\/jats:p>","DOI":"10.1021\/acsabm.6c00543","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:12:51Z","timestamp":1785849171000},"page":"8013-8029","source":"Crossref","is-referenced-by-count":0,"title":["Engineering IL-10-Overexpressing MSCs via a Non-Viral PEG-PEI Nanoplatform for Potent Therapy of Inflammatory Bowel Disease"],"prefix":"10.1021","volume":"9","author":[{"given":"Wenting","family":"Zhang","sequence":"first","affiliation":[{"name":"Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jing","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, College of Life Sciences, Nanjing Normal University , , , ,","place":["Nanjing, Jiangsu Province, China, 210008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Tang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , , ,","place":["Nanjing, Jiangsu Province, China, 211100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudi","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Medical School, Nanjing University , , ,","place":["Nanjing, P. R. China, 210093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Medical School, Nanjing University , , ,","place":["Nanjing, P. R. China, 210093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Medical School, Nanjing University , , ,","place":["Nanjing, P. R. China, 210093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , , , ,","place":["Nanjing, Jiangsu Province, China, 210008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Xie","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Medical School, Nanjing University , , ,","place":["Nanjing, P. R. China, 210093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-8849","authenticated-orcid":true,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , , , ,","place":["Nanjing, Jiangsu Province, China, 210009"]},{"name":"Nanjing Drum Tower Hospital, Medical School, Nanjing University , , ,","place":["Nanjing, P. R. China, 210093"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"issue":"6","key":"2026092215063501200_cit1","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","article-title":"Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities","volume":"22","author":"Galipeau","year":"2018","journal-title":"Cell Stem Cell"},{"issue":"5","key":"2026092215063501200_cit2","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.jid.2024.09.011","article-title":"Cell Therapy and the Skin: Great Potential but in Need of Optimization","volume":"145","author":"Lee","year":"2025","journal-title":"J. Invest. Dermatol."},{"issue":"30","key":"2026092215063501200_cit3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba6884","article-title":"Shattering barriers toward clinically meaningful MSC therapies","volume":"6","author":"Levy","year":"2020","journal-title":"Sci. Adv."},{"issue":"1","key":"2026092215063501200_cit4","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01099-z","article-title":"Engineered clinical-grade mesenchymal stromal cells combating SARS-CoV-2 omicron variants by secreting effective neutralizing antibodies","volume":"13","author":"Wang","year":"2023","journal-title":"Cell Biosci."},{"issue":"1","key":"2026092215063501200_cit5","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-022-00325-9","article-title":"Interleukin-10 genetically modified clinical-grade mesenchymal stromal cells markedly reinforced functional recovery after spinal cord injury via directing alternative activation of macrophages","volume":"27","author":"Gao","year":"2022","journal-title":"Cell. Mol. Biol. Lett."},{"issue":"1","key":"2026092215063501200_cit6","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01987-1","article-title":"Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives","volume":"29","author":"Rahimi Darehbagh","year":"2024","journal-title":"Eur. J. Med. Res."},{"issue":"35","key":"2026092215063501200_cit7","doi-asserted-by":"publisher","first-page":"45989","DOI":"10.1021\/acsami.4c08174","article-title":"Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization","volume":"16","author":"Huang","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"issue":"1","key":"2026092215063501200_cit8","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02935-8","article-title":"A long-term anti-inflammation markedly alleviated high-fat diet-induced obesity by repeated administrations of overexpressing IL10 human umbilical cord-derived mesenchymal stromal cells","volume":"13","author":"Wang","year":"2022","journal-title":"Stem Cell Res. Ther."},{"issue":"2","key":"2026092215063501200_cit9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1021\/acschembio.7b00680","article-title":"The Promise and Challenge of In Vivo Delivery for Genome Therapeutics","volume":"13","author":"Wilson","year":"2018","journal-title":"ACS Chem. Biol."},{"issue":"7","key":"2026092215063501200_cit10","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1016\/j.xphs.2021.03.024","article-title":"Manufacturing Challenges and Rational Formulation Development for AAV Viral Vectors","volume":"110","author":"Srivastava","year":"2021","journal-title":"J. Pharm. Sci."},{"issue":"3","key":"2026092215063501200_cit11","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"2026092215063501200_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120375","article-title":"Gene therapy: Comprehensive overview and therapeutic applications","volume":"294","author":"Sayed","year":"2022","journal-title":"Life Sci."},{"issue":"1","key":"2026092215063501200_cit13","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02537-w","article-title":"Engineered basic fibroblast growth factor-overexpressing human umbilical cord-derived mesenchymal stem cells improve the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery of spinal cord injury by activating the PI3K-Akt-GSK-3\u03b2 signaling pathway","volume":"12","author":"Huang","year":"2021","journal-title":"Stem Cell Res. Ther."},{"issue":"1","key":"2026092215063501200_cit14","doi-asserted-by":"publisher","DOI":"10.1007\/s10142-025-01746-3","article-title":"Epigenetic silencing of MSTN via m6A modification underlies the renoprotective effects of engineered MSC exosomes with RBM15 depletion in diabetic nephropathy","volume":"25","author":"Dong","year":"2025","journal-title":"Funct. Integr. Genomics"},{"issue":"10","key":"2026092215063501200_cit15","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.2174\/1567201819666220117102658","article-title":"Lipid-based Nanoparticles for the Targeted Delivery of Anticancer Drugs: A Review","volume":"19","author":"Khodaverdi","year":"2022","journal-title":"Curr. Drug Delivery"},{"issue":"1","key":"2026092215063501200_cit16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50980-w","article-title":"Non-viral vector based gene transfection with human induced pluripotent stem cells derived cardiomyocytes","volume":"9","author":"Tan","year":"2019","journal-title":"Sci. Rep."},{"key":"2026092215063501200_cit17","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2024.21","article-title":"Cell therapy in Sj\u00f6gren's syndrome: opportunities and challenges","volume":"26","author":"Lu","year":"2024","journal-title":"Expert Rev. Mol. Med."},{"key":"2026092215063501200_cit18","doi-asserted-by":"publisher","first-page":"843","DOI":"10.2147\/IJN.S17155","article-title":"Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells","volume":"6","author":"Chen","year":"2011","journal-title":"Int. J. Nanomedicine"},{"issue":"1","key":"2026092215063501200_cit19","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1097\/WNR.0000000000001752","article-title":"PEG-PEI\/siROCK2 inhibits A\u03b242-induced microglial inflammation via NLRP3\/caspase 1 pathway","volume":"33","author":"Liu","year":"2022","journal-title":"Neuroreport"},{"issue":"36","key":"2026092215063501200_cit20","doi-asserted-by":"publisher","DOI":"10.1002\/advs202415840","article-title":"WSGC@FA@PEG\/PEI-SPIONs Mitigate Chemoresistance in Gastric Adenocarcinoma by Modulating the Notch Signaling Pathway and Mitophagy","volume":"12","author":"Song","year":"2025","journal-title":"Adv. Sci."},{"key":"2026092215063501200_cit21","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.jconrel.2023.09.001","article-title":"Polyethylenimine (PEI) in gene therapy: Current status and clinical applications","volume":"362","author":"Casper","year":"2023","journal-title":"J. Control. Release"},{"issue":"19","key":"2026092215063501200_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202307679","article-title":"Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death","volume":"36","author":"He","year":"2024","journal-title":"Adv. Mater."},{"key":"2026092215063501200_cit23","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2267-9","article-title":"The effects of transfection reagent polyethyleneimine (PEI) and non-targeting control siRNAs on global gene expression in human aortic smooth muscle cells","volume":"17","author":"Raof","year":"2016","journal-title":"BMC Genomics"},{"issue":"1","key":"2026092215063501200_cit24","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-023-01008-7","article-title":"Therapeutic potential of mesenchymal stem\/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy","volume":"28","author":"Saadh","year":"2023","journal-title":"Eur. J. Med. Res."},{"issue":"12","key":"2026092215063501200_cit25","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: from 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"1","key":"2026092215063501200_cit26","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-02140-8","article-title":"Editorial Expression of Concern: Therapeutic potential of mesenchymal stem\/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy","volume":"29","author":"Saadh","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"2026092215063501200_cit27","first-page":"186","article-title":"Research progress of mesenchymal stem cell-derived exosomes in the treatment of inflammatory bowel disease","volume":"39","author":"Song","year":"2023","journal-title":"Cell. Mol. Immunol."},{"issue":"4","key":"2026092215063501200_cit28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.2174\/1566523220666200607190339","article-title":"Mesenchymal Stem Cells: A New Generation of Therapeutic Agents as Vehicles in Gene Therapy","volume":"20","author":"Gharbavi","year":"2020","journal-title":"Curr. Gene Ther."},{"issue":"1","key":"2026092215063501200_cit29","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-024-00355-0","article-title":"Regulation of intestinal epithelial homeostasis by mesenchymal cells","volume":"44","author":"Kayama","year":"2024","journal-title":"Inflamm. Regen."},{"issue":"6","key":"2026092215063501200_cit30","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/cdd.2009.187","article-title":"Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis","volume":"17","author":"S\u00e9mont","year":"2010","journal-title":"Cell Death Differ."},{"key":"2026092215063501200_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114121","article-title":"A cell-free TLR5(high) MSC membrane nanoparticle therapy for Crohn's disease: Targeted immunomodulation via the flagellin\/TLR5 axis","volume":"386","author":"Xie","year":"2025","journal-title":"J. Control. Release"},{"issue":"11","key":"2026092215063501200_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70075","article-title":"Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease","volume":"14","author":"Clua-Ferr\u00e9","year":"2024","journal-title":"Clin. Transl. Med."},{"issue":"6","key":"2026092215063501200_cit33","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1136\/gutjnl-2019-318264","article-title":"Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling","volume":"69","author":"Koelink","year":"2020","journal-title":"Gut"},{"key":"2026092215063501200_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2024.115039","article-title":"Plate centrifugation enhances the efficiency of polyethylenimine-based transfection and lentiviral infection","volume":"330","author":"Yang","year":"2024","journal-title":"J. Virol. Methods"},{"issue":"13","key":"2026092215063501200_cit35","doi-asserted-by":"publisher","first-page":"5330","DOI":"10.1021\/acs.nanolett.2c01316","article-title":"Defined positive charge patterns created on DNA nanostructures determine cellular uptake efficiency","volume":"22","author":"Shi","year":"2022","journal-title":"Nano Lett."},{"issue":"8","key":"2026092215063501200_cit36","doi-asserted-by":"publisher","first-page":"7078","DOI":"10.1166\/jnn.2011.4863","article-title":"Evaluation of PEG-transferrin-PEI nanocomplex as a gene delivery agent","volume":"11","author":"Lee","year":"2011","journal-title":"J. Nanosci. Nanotechnol."},{"issue":"4","key":"2026092215063501200_cit37","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1021\/bc025529v","article-title":"Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system","volume":"13","author":"Petersen","year":"2002","journal-title":"Bioconjug. Chem."},{"issue":"1","key":"2026092215063501200_cit38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/mt.2010.233","article-title":"Properties of PEI-based polyplex nanoparticles that correlate with their transfection efficacy","volume":"19","author":"Ulasov","year":"2011","journal-title":"Mol. Ther."}],"container-title":["ACS Applied Bio Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsabm.6c00543","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8013\/66310120\/mt-2026-00543v.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8013\/66310120\/mt-2026-00543v.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:29:06Z","timestamp":1790105346000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article\/9\/17\/8013\/5235641\/Engineering-IL-10-Overexpressing-MSCs-via-a-Non"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,7,28]]},"published-print":{"date-parts":[[2026,9,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acsabm.6c00543","relation":{},"ISSN":["2576-6422"],"issn-type":[{"value":"2576-6422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}