Figure 4
Figure 4. Blockade of NF-κB activation in BM-MSCs reduces in vivo leukemia burden. (A) A mixture of Matrigel, ECFCs, and either MSC-Control or MSC-IκBα-SR were injected subcutaneously into contralateral flanks of NOD/SCID/IL-2rγ−null mice (a representative example of 2 independent experiments with 4 mice, n = 8, is shown). NALM6-luciferase-CopGFP leukemia cells were intravenously transplanted into the mice, and tumor burden was monitored throughout the experiment by bioluminescence imaging with the IVIS system. Ten days after leukemia cell engraftment, mice were administered VCR for another 10 days. (B) Animals were imaged and analyzed for luciferase signal (upper) right before chemotherapy treatment started (day 10) and (lower) on the last day of treatment (day 20). (C) (Upper) Both extramedullary bones from each mouse were surgically removed at the end of the experiment, and (lower) the intensity of signal irradiating from them was quantified and plotted. (D) Average radiance measurement of luciferase signal corresponding to extramedullary bone areas derived from MSC-Control or MSC-IκBα-SR before and after 10 days of treatment with VCR, indicating a decrease in leukemia burden in extramedullary bones derived from MSC-IκBα-SR. Average radiance is expressed as photons per second per centimeter squared per steradian (p/s/cm2/sr). *Statistically significant difference at P ≤ .05. (E) Immunohistochemical analysis of artificial BM sections stained with hematoxylin and eosin or anti-luciferase antibody.

Blockade of NF-κB activation in BM-MSCs reduces in vivo leukemia burden. (A) A mixture of Matrigel, ECFCs, and either MSC-Control or MSC-IκBα-SR were injected subcutaneously into contralateral flanks of NOD/SCID/IL-2rγ−null mice (a representative example of 2 independent experiments with 4 mice, n = 8, is shown). NALM6-luciferase-CopGFP leukemia cells were intravenously transplanted into the mice, and tumor burden was monitored throughout the experiment by bioluminescence imaging with the IVIS system. Ten days after leukemia cell engraftment, mice were administered VCR for another 10 days. (B) Animals were imaged and analyzed for luciferase signal (upper) right before chemotherapy treatment started (day 10) and (lower) on the last day of treatment (day 20). (C) (Upper) Both extramedullary bones from each mouse were surgically removed at the end of the experiment, and (lower) the intensity of signal irradiating from them was quantified and plotted. (D) Average radiance measurement of luciferase signal corresponding to extramedullary bone areas derived from MSC-Control or MSC-IκBα-SR before and after 10 days of treatment with VCR, indicating a decrease in leukemia burden in extramedullary bones derived from MSC-IκBα-SR. Average radiance is expressed as photons per second per centimeter squared per steradian (p/s/cm2/sr). *Statistically significant difference at P ≤ .05. (E) Immunohistochemical analysis of artificial BM sections stained with hematoxylin and eosin or anti-luciferase antibody.

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