Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

Skin has the natural ability to heal and replace dead cells regulated by a network of complex immune processes. This ability is conferred by the population of resident immune cells that act in coordination with other players to provide a homeostatic environment under constant challenge. Other than providing structure and integrity, the epidermis and dermis also house distinct immune properties. The dermal part is represented by fibroblasts and endothelial cells followed by an array of immune cells which includes dendritic cells (DCs), macrophages, mast cells, NK-cells, neutrophils, basophils, eosinophils, αβ T lymphocytes, B-cells and platelets. On the other hand, the functionally active immune cells in the epidermis comprise keratinocytes, DCs, NKT-cells, γδ T cells and αβ T cells (CD4+ and CD8+). Keratinocytes create a unique microenvironment for the cells of the immune system by promoting immune recognition and cellular differentiation. T lymphocytes exhibit tissue-specific tropism toward the epidermis and the lymphatic drainage system important for their function in immune regulation. This diversity in immune regulators makes the skin a unique organ to overcome pathogenic or foreign invasion. In addition, the highly coordinated molecular events make the skin an attractive model to understand and explore its regenerative potential.

Use of paracrine factors from stem cells to treat local radiation burns in rats Andrey Temnov,1–3 Tatyana Astrelina,1–3 Konstantin Rogov,1–3 Boris Moroz,1–3 Vladimir Lebedev,1–3 Tamara Nasonova,1–3 Alla Lyrshchikova,1–3 Olga Dobrynina,1–3 Yury Deshevoy,1–3 Alexander Melerzanov,3 Augustinus Bader,4 Apurva Mishra,3 Shibashish Giri,4,5 Valeriy Boyarintsev,1–3 Alexander Trofimenko,1–3 Andrey Bushmanov,1–3 Alexander Samoylov1–3 1State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow, Russia; 2Research Institute of Human Morphology, Russian Academy of Medical Science, Moscow, Russia; 3Faculty of Biological and Medical Physics. Moscow Institute of Physics and Technology (MIPT), Moscow Region, Russia; 4Applied Stem Cell Biology and Cell Technology, Biomedical and Biotechnological Center, Leipzig University, Leipzig, Germany; 5Department of Plastic and Hand Surgery, University Hospital Rechts der Isar, Munich Technical University, Munich, Germany Background: Mesenchymal stem cells based paracrine bioactive factors that deploy their task as an essential mechanism, but their efficiency for skin regeneration still requires clarification. Methods: The mesenchymal stem cell-based paracrine factors were administered by subcutaneous injection of 0.5 mL peptides (general protein 8 mg/mL). These were performed after radiation on different days like the first, third, sixth, eighth, and 10th. To determine the consequences, we performed photography, planimetry, and preclinical test each week after 15 days of radiation. MSC-based peptides were injected into a rat that had radiation burns, and its observation encouraged cell-free therapeutic remedies to regenerate skin. Both control and experimental groups were exposed to 110 Gy of X-rays, which resulted in the formation of localized radiation burns on the skin (S=6 cm2) 15 days later. Thirty days after radiation, the wound stabilized (surface of the wound was S=2.2±0.2 cm2) and fluctuated throughout the course of the pathological process.Results: The wounded area on the skin from the 15th to the 29th day after radiation was practically the same in both groups. The wounded area gradually reduced by 6.1±0.4 cm2 (experimental group) and 5.9±0.6 cm2 (control group) 15 days after radiation up to 2.2±0.3 cm2 (in both control and experimental groups) on the 29th day after radiation. However, starting from the 36th day, there was a constant reduction in the burn area in the experimental group up to 0.2±0.1 cm2 till the 71st day after radiation. Conclusion: In the control group, the area of the lesion ranged from 1.4±0.6 cm2 on the 50th day to 1.9±0.8 cm2 on the 71st day. During the 57th to the 71st day, the difference between the affected area in the experimental and control groups was 1:8. The experimental group has a significantly higher level of skin regeneration and significant decrease in the level of leukocyte infiltration, thereby reducing necrosis. Keywords: Mesenchymal stem cells, MSC-based paracrine factors, radiation burn, skin regeneration

An overview of the architecture, regulatory documents and Internet sources on the digital transformation of occupational medicine, state IT platforms, the architecture of interdepartmental, interdisciplinary information interaction of IT systems, the formation of large user data, the use of risk management in functional personalized 4P medicine is presented. The principles of the formation of a unified information and analytical system “Occupational Medicine” are described.