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Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells

DC Field Value Language
dc.contributor.authorKim, Irene-
dc.contributor.authorPark, Hyomin-
dc.contributor.authorHwang, Injoo-
dc.contributor.authorMoon, Dodam-
dc.contributor.authorYun, Hyunji-
dc.contributor.authorLee, Eun Ju-
dc.contributor.authorKim, Hyo-Soo-
dc.date.accessioned2021-08-20T01:58:02Z-
dc.date.available2021-08-20T10:59:10Z-
dc.date.issued2021-07-01-
dc.identifier.citationCell & Bioscience. 2021 Jul 01;11(1):120ko_KR
dc.identifier.issn2045-3701-
dc.identifier.urihttps://hdl.handle.net/10371/174808-
dc.description.abstractBackground
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 dont 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.
ko_KR
dc.description.sponsorshipThis work was supported by the Korea Health Technology R&D Project Strategic Center of Cell and Bio Therapy [Grant number HI17C2085] and Korea Research-Driven Hospital [Grant number HI14C1277] through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (MHW), Republic of Korea. The funders had no role in the study design, data collection and analysis, deci‑sion to publish, or preparation of the manuscript.ko_KR
dc.language.isoenko_KR
dc.subjectActive chemerin-
dc.subjectChemoattractant-
dc.subjectIntravascularly-delivery-
dc.subjectHoming of stem cells-
dc.titleDiscovery of chemerin as the new chemoattractant of human mesenchymal stem cellsko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor박효민-
dc.contributor.AlternativeAuthor황인주-
dc.contributor.AlternativeAuthor문도담-
dc.contributor.AlternativeAuthor윤현지-
dc.contributor.AlternativeAuthor김효수-
dc.identifier.doi10.1186/s13578-021-00631-3-
dc.citation.journaltitleCell & Bioscienceko_KR
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2021-07-04T03:23:50Z-
dc.citation.number1ko_KR
dc.citation.startpage120ko_KR
dc.citation.volume11ko_KR
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