Small extracellular vesicles-derived from 3d cultured human nasal mucosal mesenchymal stem cells during differentiation to dopaminergic progenitors promote neural damage repair via miR-494–3p after manganese exposed mice

Xin Yang; Xueting Wang; Jiao Xia; Jiaxin Jia; Shixuan Zhang; Weiwei Wang; Weifeng He; Xin Song; Li Chen; Piye Niu; Tian Chen

Ecotoxicology and Environmental Safety (Jul 2024)

Small extracellular vesicles-derived from 3d cultured human nasal mucosal mesenchymal stem cells during differentiation to dopaminergic progenitors promote neural damage repair via miR-494–3p after manganese exposed mice

Xin Yang,
Xueting Wang,
Jiao Xia,
Jiaxin Jia,
Shixuan Zhang,
Weiwei Wang,
Weifeng He,
Xin Song,
Li Chen,
Piye Niu,
Tian Chen

Affiliations

Xin Yang: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Xueting Wang: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Jiao Xia: Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China
Jiaxin Jia: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Shixuan Zhang: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Weiwei Wang: Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China
Weifeng He: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Xin Song: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Li Chen: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Piye Niu: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Correspondence to: School of Public Health, Capital Medical University, Beijing 100069, China.
Tian Chen: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Correspondence to: School of Public Health, Capital Medical University, Beijing 100069, China.

Journal volume & issue: Vol. 280
p. 116569

Abstract

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Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494–3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494–3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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