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. 2019 Jul 4;45:39–57. doi: 10.1016/j.ebiom.2019.06.047

Fig. 5.

Fig. 5

Engineered MSC exhibit therapeutic effects in treating bone metastases in vivo in the MDA-MB231 intratibial model. (a) Timeline of the therapeutic treatment validation. MSC were engineered as follows: Mock group (Mock transfected), CD group (PSGL-1/SLEX/CD), OPG group (PSGL-1/SLEX/OPG) and CD/OPG group (PSGL-1/SLEX/CD/OPG) and injected directly into the tibia, n = 10 per group. PBS group only received PBS in the tibia instead of MSC, n = 6. (b) The logarithm values of the tumour growth ratio (Total photon flux measured/Total photon flux on the day before the treatment started) are plotted over time for each group. Median of each group is shown. Pink double-headed arrow shows treatment duration. Statistical analysis: Kruskal-Wallis with Dunn's multiple comparison post hoc, * p ≤ .05 between Mock MSC and OPG MSC. (c) Bar graph shows the tumour growth ratio measured on the day after the treatment is done. Each point represents one animal, and the bars represent the median value of the group. Dashed line indicates a tumour growth ratio of 1 (animals below that line have tumour decrease). Statistical analysis: Kruskal-Wallis with Dunn's multiple comparison post hoc, * p ≤ .05 between Mock MSC and CD/OPG MSC. (d) Bar graph shows the tumour growth ratio measured on the end-point day. Each point represents one animal, and the bars represent the median value of the group. Statistical analysis: Kruskal-Wallis with Dunn's multiple comparison post hoc, * p ≤ .05 between Mock MSC and OPG MSC. (e) MicroCT imaging was done on mouse tibias after euthanasia. Representative 3D reconstructions matching the median of each group for bone analysis are shown. First row shows whole tibias without the fibula, while bottom row shows trabecular bone. (f) Bar graph shows the trabecular bone ratio measured by normalising the trabecular bone volume of each tumour leg to the trabecular bone volume of healthy legs. Each point represents one animal, and the bars represent the median value of the group. Statistical analysis: Kruskal-Wallis with Dunn's multiple comparison post hoc, * p ≤ .05 between Mock MSC and OPG MSC. (g) H&E staining of mouse tibias at end-point demonstrate treatment with OPG MSC and CD/OPG MSC can clear tumour cells and preserve the bone structure, while tumour invades the cortical bone in control animals (PBS and Mock MSC groups). 5 representative mouse tibias are shown for each group. BM = healthy bone marrow. Scale bar: 500 μm. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)