| Title |
InVivo Bioluminescence Imaging of Transplanted Mesenchymal Stromal Cells and Their Rejection Mediated by Intrahepatic NK Cells
|
|---|---|
| Published in |
Molecular Imaging and Biology, July 2016
|
| DOI | 10.1007/s11307-016-0962-9 |
| Pubmed ID | |
| Authors |
Jing-jing Liu, Xiao-jun Hu, Zheng-ran Li, Rong-hua Yan, Dan Li, Jin Wang, Hong Shan |
| Abstract |
Mesenchymal stromal cells (MSCs) hold promise in the treatment of liver disease. However, short survival time of MSCs after intrahepatic transplantation limits their value; therefore, understanding the basis of MSCs survival and rejection may increase their utility. This study was aimed at determining the role of intrahepatic natural killer (NK) cells on MSCs survival and their retention in the liver shortly after transplant. Human MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R), and the residence time and survival of MSCs-R xenografts after intrahepatic transplantation were evaluated by in vivo bioluminescence imaging (BLI). Coculture of MSCs and NK cells was performed to assess cytotoxicity. To evaluate the role of NK cells in rejection of the xenografted cells, the fates of transplanted MSCs-R were then assessed in vivo by BLI after activation of intrahepatic NK cells. We observed a linear correlation between luciferase activity from live MSCs-R and cell number in vitro (R (2) = 0.9956). In vivo, we observed a gradual decline in bioluminescent signals from transplanted MSCs-R over a region corresponding to the liver in both the control group and the NK-activated group. However, the survival time and retention of intrahepatic MSCs-R decreased more rapidly in the NK-activated group of mice compared to the control group. This indicated that activated NK cells accelerate the elimination of transplanted MSCs. Also, we found that the number of hepatic NK cells and the expression of NK activation markers significantly increased after intrahepatic delivery of MSCs. This suggested that resident NK cells, in a resting state, were activated by intrahepatic transplantation of human MSCs. Taken together, the data suggests that activated hepatic NK cells mediate, in part, rejection of the MSCs xenografts. Cytotoxicity assays showed that activated NK cells may inhibit the proliferation of MSCs and, to a certain extent, induce MSCs death. Human MSCs could be followed dynamically in vivo by BLI, and the role of murine hepatic NK cells, especially activated NK cells, could be inferred from the loss of signals from MSCs. This finding may have practical clinical implications in MSCs transplantation in treating liver disease. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 3 | 12% |
| Student > Doctoral Student | 3 | 12% |
| Student > Master | 2 | 8% |
| Researcher | 2 | 8% |
| Librarian | 1 | 4% |
| Other | 5 | 20% |
| Unknown | 9 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 28% |
| Biochemistry, Genetics and Molecular Biology | 3 | 12% |
| Agricultural and Biological Sciences | 2 | 8% |
| Immunology and Microbiology | 2 | 8% |
| Unspecified | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 9 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2016.
All research outputs
#22,759,452
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Outputs from Molecular Imaging and Biology
#687
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Outputs of similar age
#327,301
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Outputs of similar age from Molecular Imaging and Biology
#10
of 19 outputs
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