Mesenchymal Stem Cell Fates in Murine Acute Liver Injury and Chronic Liver Fibrosis Induced by Carbon Tetrachloride
文献类型：期刊论文
| 作者 | Ma, Chenhui1,2; Han, Li1,2; Wu, Jiajun1,2; Tang, Feng1,2; Deng, Qiangqiang2; He, Ting2,3; Wu, Zhitao2; Ma, Chen1,2; Huang, Wei1,2; Huang, Ruimin1,2
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| 刊名 | DRUG METABOLISM AND DISPOSITION
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| 出版日期 | 2022-10-01 |
| 卷号 | 50期号:10页码:1352-1360 |
| ISSN号 | 0090-9556 |
| DOI | 10.1124/dmd.122.000958 |
| 通讯作者 | Huang, Wei(huangwei@simm.ac.cn) ; Huang, Ruimin(rmhuang@simm.ac.cn) ; Pan, Guoyu(gypan@simm.ac.cn) |
| 英文摘要 | Mesenchymal stemcells (MSCs) therapy has shown potential benefits in multiple diseases. However, their clinic performance is not as satisfactory as expected. This study aimed to provide an alternative explanation by comparing MSCs' fates in different liver diseases. The distribution and therapeutic effects of human MSC (hMSCs) were investigated in acute liver injury (ALI) and chronic liver fibrosis (CLF) mice models, respectively. The two models were induced by single or repeated injection of carbon tetrachloride separately. The increase of hMSCs exposure in the liver (AUC(liver 0-72 hour)) were more significant in ALI than in CLF (177.1% versus 96.2%). In the ALImodel, the hMSCs exposures in the lung (AUC(lung 0-72 hour)) increased by nearly 50%, whereas it decreased by 60.7% in CLF. The efficacy satellite study indicated that hMSCs could significantly ameliorate liver injury in ALI, but its effects in CLF were limited. In the ALI, suppressed natural killer (NK) cell activities were observed, while NK cell activities were increased in CLF. The depletion of NK cells could increase hMSCs exposure in mice. For mice MSC (mMSCs), their cell fates in ALI were very similar to hMSCs in ALI: mMSCs' exposure in the liver and lung increased in ALI. In conclusion, our study revealed the distinct cell pharmacokinetic patterns of MSCs in ALI and CLF mice, which might be at least partially attributed to the different NK cell activities in the two liver diseases. This finding provided a novel insight into the varied MSCs' therapeutic efficacy in the clinic. SIGNIFICANCE STATEMENT Currently, there is little knowledge about the PK behavior of cell products like MSCs. This study was the first time investigating the influence of liver diseases on cell fates and efficacies of MSCs and the underneath rationale. The exposure was distinct between two representative liver disease models, which directly linked with the therapeutic performance that MSCs achieved. The difference could be attributed to the NK cells-mediated MSCs clearance. |
| WOS关键词 | NATURAL-KILLER-CELLS ; STROMAL CELLS ; NK CELLS ; IDENTIFICATION ; CIRRHOSIS |
| 资助项目 | Organ Reconstruction and Manufacturing Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020205] ; National Natural Science Foundation of China[81872927] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000888793300004 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304398]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Wei; Huang, Ruimin; Pan, Guoyu |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Shanghai Inst Mat Medica, Chinese Acad Sci, Shanghai, Peoples R China 3.Nanjing Tech Univ, Sch Pharmaceut Sci, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Chenhui,Han, Li,Wu, Jiajun,et al. Mesenchymal Stem Cell Fates in Murine Acute Liver Injury and Chronic Liver Fibrosis Induced by Carbon Tetrachloride[J]. DRUG METABOLISM AND DISPOSITION,2022,50(10):1352-1360. |
| APA | Ma, Chenhui.,Han, Li.,Wu, Jiajun.,Tang, Feng.,Deng, Qiangqiang.,...&Pan, Guoyu.(2022).Mesenchymal Stem Cell Fates in Murine Acute Liver Injury and Chronic Liver Fibrosis Induced by Carbon Tetrachloride.DRUG METABOLISM AND DISPOSITION,50(10),1352-1360. |
| MLA | Ma, Chenhui,et al."Mesenchymal Stem Cell Fates in Murine Acute Liver Injury and Chronic Liver Fibrosis Induced by Carbon Tetrachloride".DRUG METABOLISM AND DISPOSITION 50.10(2022):1352-1360. |
入库方式： OAI收割
来源：上海药物研究所
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