首页|Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

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Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct re-gion,limiting their therapeutic efficacy and clinical translation.High levels of deadly reactive oxygen rad-icals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs'viability.Based on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy.This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer.In this system,extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation.Meanwhile,the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing.The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days.This vitality-augmented system demonstrates the poten-tial to accelerate the clinical translation of MSC treatment and boost stroke recovery.

Ischemic strokeMesenchymal stem cellCell engineeringHormesis effectBioorthogonal chemistryMicrogliaReactive oxygen spicesProinflammatory cytokines

Jianpei Xu、Yinzhe Sun、Yang You、Yuwen Zhang、Dan Huang、Songlei Zhou、Yipu Liu、Shiqiang Tong、Fenfen Ma、Qingxiang Song、Chengxiang Dai、Suke Li、Jigang Lei、Zhihua Wang、Xiaoling Gao、Jun Chen

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Shanghai Pudong Hospital & Department of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai 201203,China

Key Laboratory of Smart Drug Delivery,Ministry of Education,School of Pharmacy,Fudan University,Shanghai 201203,China

Institute of Science and Technology for Brain-Inspired Intelligence & Department of Neurology,Fudan University,Shanghai 201203,China

Department of Rehabilitation Medicine,Huashan Hospital,Fudan University,Shanghai 201203,China

Department of Pharmacology and Chemical Biology,State Key Laboratory of Oncogenes and Related Genes,Shanghai Universities Collaborative Innovation Center for Translational Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

Daxing Research Institute,University of Science and Technology Beijing,Biomedical Industry Base,Zhongguancun Science and Technology Park,Beijing 102600,China

Cellular Biomedicine Group Inc.,Shanghai 201210,China

Department of Emergency,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399,China

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国家自然科学基金国家自然科学基金国家自然科学基金上海市科委项目上海市科委项目Programs of Shanghai Academic/Technology Research LeaderPrograms of Shanghai Academic/Technology Research Leader上海市教委科研创新计划fund of Research Grant for Health Science and Technology of Shanghai Municipal Commission of Health CommitteeScience and Technology Development Fund of Shanghai Pudong New AreaProject of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University

92068110819732729206811120JC141180023S4190010021XD140020021XD14222002023Z-KZD2120214Y0268PKJ2020-Y49Zdzk2020-15

2024

10.1016/j.apsb.2023.11.009

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(3)
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