The SSL scaffolds provide a beneficial microenvironment for the osteogenic MSCs' differentiation in vitro and support de novo bone formation in vivo.

IntroductionIn recent years, mesenchymal stem cells (MSCs) have been demonstrated to play an important role in carcinogenesis. However, the effect of MSCs on tumor and metastasis development and the mechanisms underlying the interaction of cancer and stem cells are not completely understood. This study investigated the effect of MSCs on breast cancer metastasis formation by using the methods of in vivo fluorescence and luminescence imaging.MethodsMSCs were isolated from bone marrow of normal donors, characterized, and genetically labeled with luciferase (luc2). The effects of MSCs on MDA-MB-231 cancer cell proliferation were evaluated in conditioned medium from MSCs. To generate lung metastases, MDA-MB-231 cells stably expressing red fluorescent protein Turbo FP650 were injected intravenously into nude mice. On day 10 after the cancer cell injection, mice were injected via the tail vein with MSCs-luc2 cells (the MET + MSCs group). Animals that received the injection of MDA-MB-231-Turbo FP650 alone (the MET group) and no injections (the intact control group) served as controls. Fluorescence and bioluminescence imaging was performed for monitoring of the metastasis formation and MSC distribution in the recipient’s body.ResultsWe found that the proliferative activity of the cancer cells in the presence of MSC conditioned medium was lower than that of the cells grown in conventional culture medium. The metastasis formation in the MET + MSCs group was delayed in time as compared with the MET group. Macroscopic and histological examination of isolated lungs 8 weeks after cancer cell injection showed that the total number of metastases in animals of the MET + MSCs group was significantly lower. Using bioluminescence imaging in vivo, we found that MSCs-luc2 cells survived in the host animal for at least 7 weeks and re-migrated to the lung 6 to 7 weeks after injection. Immunohistochemical analysis revealed the presence of MSCs-luc2 in metastases and lung tissue.ConclusionsLong-term in vivo bioluminescence imaging of intravenously injected MSCs-luc2 cells showed distribution of MSCs to the lungs and abdominal organs within the first 2 to 3 weeks and re-migration to the lungs in weeks 6 to 7. It was found that MSCs reduced the proliferative activity of cancer cells in vitro and lung metastasis formation in mice.

The combined use of fluorescence cystoscopy and cross-polarization optical coherence tomography (CP OCT) with quantitative estimation of the OCT signal was assessed in 92 bladder zones. It demonstrated the diagnostic accuracy in detecting superficial bladder cancer of 93.6%, sensitivity 96.4%, specificity 92.1%, positive predictive value 87% and negative predictive value 97.9%. Quantitative estimation of OCT signal standard deviation in cross-polarization (CP OCT SD index) makes the visual criteria of CP OCT image assessment more objective. The level of CP OCT SD index for diagnosing superficial bladder cancer, including cancer in situ, was 4.32 dB and lower. When tumor is located on a postoperative scar, CP OCT SD index may be higher than the threshold level of 4.32 dB due to strong scattering and depolarization in scar fibrous tissue. A high inverse correlation was found between CP OCT SD index and the level expressed by p63, Ki-67, p53, CD44v6 markers.

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