Background： Biotherapy based on human bone marrow-derived mesenchymal stem cells （BMSCs） is currently the focus of research, especially in the field of autologous stem cell transplantation. A novel type of metastas...Background： Biotherapy based on human bone marrow-derived mesenchymal stem cells （BMSCs） is currently the focus of research, especially in the field of autologous stem cell transplantation. A novel type of metastasis-associated magnetic resonance （MR） molecular imaging probe was constructed, and the changes in metastasis and proliferation of hepatocellular carcinoma （HCC） before and after BMSC intervention were observed through MR imaging （MRI）. Methods：Metastasis-associatedMRmolecularimagingprobe,integrin αvβ3 ligandcRGD-PEG-DGL-DTPA-Gd （Gd-RGD）,wereconstructed. After human BMSC intervention was performed for 6weeks, tumor weight inhibition rates were calculated, and the RGD molecular probe was imaged through MRI with molecular imaging agent Gd-DTPAas control.The signal-to-noise ratio （SNR） and contrast-to-noise ratio （CNR） in the MRI experiment were used as semi-quantitative indicators. Polymerase chain reaction method was performed to detect proliferation- and metastasis-associated indicators, transforming growth factor β-1 （TGFβ1）, osteopontin （OPN）, and integrin subunit αv and β3. Results： The highest tumor weight inhibition rates were observed 3 weeks after the BMSC transplantation. The MR Gd-RGD in the HCC tissues after the BMSC intervention showed less enhancement than Gd-DTPA. The Gd-DTPAMRI of control group had higher SNR and CNR than Gd-RGD MRI in the experimental groups （P 〈 0.05）. For high metastatic potential hepatocellular carcinoma （MHCC97-H）, significant differenceswereobservedintheSNRsandCNRsofGd-RGDMRIbeforeandaftertheBMSCintervention（P〈0.05）.Forlowmetastaticpotential hepatocellular carcinoma （MHCC97-L）, the CNRs of Gd-RGD MRI were statistically different before and after BMSC intervention （P 〈 0.05）. With regard to MHCC97-H, OPN, β3, and TGFβ1 expression significantly decreased after BMSC intervention （P 〈 0.05）. In MHCC97-L and OPN, β3, TGFβ1, and αv expression after BMSC intervention decreased, and the difference was statistically significant （P 〈 0.05）. Conclusions： The CNR index of MRI is a good indicator for distinguishing high- and low-metastatic potential HCC tissues.After BMSC transplantation of MRI through the two kinds of tracer, the SNR and CNR indexes can distinguish two kinds of high and low metastatic potential HCC tissues, and Gd-RGD imaging is more suitable in distinguishing the metastatic potential changes through BMSC intervention.展开更多
文摘Background： Biotherapy based on human bone marrow-derived mesenchymal stem cells （BMSCs） is currently the focus of research, especially in the field of autologous stem cell transplantation. A novel type of metastasis-associated magnetic resonance （MR） molecular imaging probe was constructed, and the changes in metastasis and proliferation of hepatocellular carcinoma （HCC） before and after BMSC intervention were observed through MR imaging （MRI）. Methods：Metastasis-associatedMRmolecularimagingprobe,integrin αvβ3 ligandcRGD-PEG-DGL-DTPA-Gd （Gd-RGD）,wereconstructed. After human BMSC intervention was performed for 6weeks, tumor weight inhibition rates were calculated, and the RGD molecular probe was imaged through MRI with molecular imaging agent Gd-DTPAas control.The signal-to-noise ratio （SNR） and contrast-to-noise ratio （CNR） in the MRI experiment were used as semi-quantitative indicators. Polymerase chain reaction method was performed to detect proliferation- and metastasis-associated indicators, transforming growth factor β-1 （TGFβ1）, osteopontin （OPN）, and integrin subunit αv and β3. Results： The highest tumor weight inhibition rates were observed 3 weeks after the BMSC transplantation. The MR Gd-RGD in the HCC tissues after the BMSC intervention showed less enhancement than Gd-DTPA. The Gd-DTPAMRI of control group had higher SNR and CNR than Gd-RGD MRI in the experimental groups （P 〈 0.05）. For high metastatic potential hepatocellular carcinoma （MHCC97-H）, significant differenceswereobservedintheSNRsandCNRsofGd-RGDMRIbeforeandaftertheBMSCintervention（P〈0.05）.Forlowmetastaticpotential hepatocellular carcinoma （MHCC97-L）, the CNRs of Gd-RGD MRI were statistically different before and after BMSC intervention （P 〈 0.05）. With regard to MHCC97-H, OPN, β3, and TGFβ1 expression significantly decreased after BMSC intervention （P 〈 0.05）. In MHCC97-L and OPN, β3, TGFβ1, and αv expression after BMSC intervention decreased, and the difference was statistically significant （P 〈 0.05）. Conclusions： The CNR index of MRI is a good indicator for distinguishing high- and low-metastatic potential HCC tissues.After BMSC transplantation of MRI through the two kinds of tracer, the SNR and CNR indexes can distinguish two kinds of high and low metastatic potential HCC tissues, and Gd-RGD imaging is more suitable in distinguishing the metastatic potential changes through BMSC intervention.
基金financially supported by the National Natural Science Foundation of China(Nos.20931003 and 21071068)the National Science Foundation for Fostering Talents in Basic Research of the National Natural Science Foundation of China(No. J1103307)
文摘Received 23 November 2012 Received in revised form 13 December 2012 Accepted 18 December 2012 Available online 20 January 2013
