title: Upregulation of CC Chemokine Receptor 7 (CCR7) Enables Migration of Xenogeneic Human Adipose-Derived Mesenchymal Stem Cells to Rat Secondary Lymphoid Organs.
abstract: BACKGROUND CC chemokine receptor 7 (CCR7) expression is vital for cell migration to secondary lymphoid organs (SLOs). Our previous work showed that inducing CCR7 expression enabled syngeneic mesenchymal stem cells (MSCs) to migrate into SLOs, resulting in enhanced immunosuppressive performance in mice. Given that human adipose-derived stem cells (hASCs) are widely used in clinical therapy, we further investigated whether upregulation of CCR7 enables xenogeneic hASCs to migrate to rat SLOs. MATERIAL AND METHODS hASCs rarely express CCR7; therefore, hASCs were transfected with lentivirus encoding rat CCR7 (rCCR7) plus green fluorescence protein (GFP) or GFP alone. CCR7 mRNA and cell surface expression of rCCR7-hASCs and GFP-hASCs were examined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM), respectively. The phenotype, differentiation, and proliferation capacity of each cell type was also determined. To examine migration, rCCR7-hASCs and GFP-hASCs were injected intravenously into Lewis rats, and the proportion of GFP-positive cells in the spleen and lymph nodes was determined with FCM. RESULTS mRNA and cell surface protein expression of CCR7 was essentially undetectable in hASCs and GFP-ASCs; however, CCR7 was highly expressed in rCCR7-ASCs. rCCR7-hASCs, GFP-hASCs, and hASCs shared a similar immunophenotype, and maintained the ability of multilineage differentiation and proliferation. In addition, the average proportion of GFP-positive cells was significantly higher following transplantation of rCCR7-hASCs compared with GFP-hASCs (p<0.01). CONCLUSIONS These results suggest that upregulation of rat CCR7 expression does not change the phenotype, differentiation, or proliferation capacity of hASCs, but does enable efficient migration of hASCs to rat SLOs.
authors.affiliation: Department of Plastic and Reconstruction, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Tian
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Vascular and Endovascular, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Shao-Liang
authors.initials: SL
authors.lastname: Luan
authors.affiliation: Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Stomatology, General Hospital of Chinese People's Armed Police Forces, Beijing, China (mainland).
authors.forename: Xing-Kun
authors.initials: XK
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Department of Plastic Surgery, The Second Hospital of ShanXi Medical University, Taiyuan, Shanxi, China (mainland).
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Han
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Beijing, China (mainland).
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstruction, Chinese PLA General Hospital, Beijing, China (mainland).
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010641:Phenotype; D011917:Rats, Inbred Lew; D054400:Receptors, CCR7 / Q000378:metabolism*; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D054400:Receptors, CCR7; D049452:Green Fluorescent Proteins