دورية أكاديمية
Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells
| العنوان: | Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells |
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| المؤلفون: | Irene Kim, Hyomin Park, Injoo Hwang, Dodam Moon, Hyunji Yun, Eun Ju Lee, Hyo-Soo Kim |
| المصدر: | Cell & Bioscience, Vol 11, Iss 1, Pp 1-15 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biotechnology LCC:Biology (General) LCC:Biochemistry |
| مصطلحات موضوعية: | Active chemerin, Chemoattractant, Intravascularly-delivery, Homing of stem cells, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436 |
| الوصف: | Abstract Background The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don’t know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver. Methods and results When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector. Conclusions Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-3701 |
| Relation: | https://doaj.org/toc/2045-3701 |
| DOI: | 10.1186/s13578-021-00631-3 |
| URL الوصول: | https://doaj.org/article/0b02c568eebc447993e826786806f701 |
| رقم الأكسشن: | edsdoj.0b02c568eebc447993e826786806f701 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20453701 |
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| DOI: | 10.1186/s13578-021-00631-3 |