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黎阳 吴燕峰 王潇娉 黄绍良 方建培 黄科 魏菁 中山大学孙逸仙纪念医院儿科 drliyang@126

The Influences of MSC Infused via Different Ways and Different Time on Anti-tumor Activities of CIK/NK cells from Umbilical Cord Blood in K562 NOD/SCID Mice. 黎阳 吴燕峰 王潇娉 黄绍良 方建培 黄科 魏菁 中山大学孙逸仙纪念医院儿科 drliyang@126.com. Background.

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黎阳 吴燕峰 王潇娉 黄绍良 方建培 黄科 魏菁 中山大学孙逸仙纪念医院儿科 drliyang@126

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  1. The Influences of MSC Infused via Different Ways and Different Time on Anti-tumor Activities of CIK/NK cells from Umbilical Cord Blood in K562 NOD/SCID Mice 黎阳 吴燕峰 王潇娉 黄绍良 方建培 黄科 魏菁 中山大学孙逸仙纪念医院儿科 drliyang@126.com

  2. Background Bone marrow mesenchymal stem cells (MSC) has a unique immunological characteristics： Low expression of classⅠMHC molecules Do not express classⅡMHC molecules Did not express Fas ligand and co-stimulatory molecules Therefore, MSC is survival possible long-term in the host body, even can be survival long-term in heterogeneity host.

  3. Background Cytokine-induced killer(CIK) cells are heterogeneous group of cells that obtained from co-cultured mononuclear cells of the human peripheral blood, cord blood or bone marrow with stimulation of variety cytokines such as IL-2, IFN-γ，Anti-CD3 in vitro after a period of time. CIK cells expressing CD3 and CD56.

  4. Background Studies have showed that MSC has a negative regulatory role, whether or not its can effect the anti-tumor activity of subsequent infused killer cells in vivo is worth being further studied.

  5. Background Because CD3+CD56+ CIK cells derived from CD3+CD56- T cells, MSC may also inhibit anti-tumor activity of CD3+CD56+ CIK cells.

  6. Objectives To explore the influences of MSC infused via different ways and at different time on anti-tumor activities of CIK/NK cells from umbilical cord blood in K562 NOD/SCID mice.

  7. Experimental priniple： Inhibition MSC CIK/NKcells infusion infusion K562 NOD/SCIDmice Shorten survival Increase in tumor burden

  8. Experimental groups： K562 After 12h After 12h Group A Group C at the same time at the same time MSC CIK/NK MSC CIK/NK (caudal vein) (caudal vein) (marrow cavity) (caudal vein) Group B Group D Delayed 48h Delayed 48h MSC CIK/NK MSC CIK/NK (caudal vein) (caudal vein) (marrow cavity) (caudal vein) NOD/SCIDmice Group E Group F Group G Delayed 48 hours CIK/NK CIK/NK K562 cells (inoculated alone) (caudal vein) (caudal vein)

  9. Detection of indicators: Calculate survival curve of each group NOD/SCID tumor-bearing mice By morphology, flow cytometry, and histopathology,to detect the tumor cell loads in peripheral blood, bone marrow, liver, spleen ,lungs and other organs.

  10. Survival time and body weight change in various group of NOD/SCID mice(x±s,n=8) Note: ▲to compare C, D, E, F set of data,there was statistically significant difference (P <0.05);         ■to compare the C, D, E, F set of data,ther was statistically significant difference (P <0.05).

  11. Kaplan-Meier survival curve in various group of NOD/SCID mice 1. the average survival time of mice in groups A and B was significantly shorter than groups C, D, E and F.2. the average survival time of mice was no significant difference between groups A and B.3. the average survival time of mice was no significant difference between groups C and D.4. the average survival time of mice was no significant difference among groups A and B and group G.

  12. Proportion of tumor cells in the liver, spleen, lung tissue homogenate in each group mice Liver, spleen, lung tissue homogenate smears: the proportion of tumor cells in mice of group A and B is higher than that of group C, D, E and F; the proportion of tumor cells in mice of group A is near to group B;the proportion of tumor cells in mice of group C is near to group D;the proportion of tumor cells in mice of group A and B is near to group G.

  13. CD33 expression level in different parts of each group (x±s，n=8)(%) CD33 expression in lung and liver tissue homogenate were significantly higher than those in peripheral blood and bone marrow in each group mice.(P＜0.05）

  14. Visible liver tumor in Group A mice Pathological section of liver tumor in group A mince (HE staining, up 40 ×; down 400 ×)

  15. Visible lung tumor in Group B mice Pathological section of lung tumor in group B mince (HE staining, up 40 ×; under 400 ×)

  16. Conclusions

  17. conclusion In vivo ,MSC may significantly inhibit anti-tumor activity of killer cell with the same way infusion. Even if infused MSC 2 days in advance, this inhibitory effect still exists.

  18. conclusion Through the tumor-bearing animal model study,it revealed that pre-entered MSC in vivo will weaken GVL effect of the CIK / NK cells. It prompts that by using MSC combine with HSCT,clearance of MRD and the GVL effect may be detrimental to patients with hematologic malignancies,and may affect anti-tumor activity of the latter infused CIK cells, NK cells or CTL, thereby increase the risk of tumor recurrence.

  19. Thanks

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