The high sensitivity of living organic forms to space radiation remains the critical issue during spaceflight, to which they will be chronically exposed during months of interplanetary or even decades of interstellar spaceflight. In the human body, all actively dividing and poorly differentiated cells are always close to being damaged by radiological or chemical agents. The chronic exposure to ionizing radiation primarily causes changes in blood counts and intestinal damage such as fibrosis, obliterative vasculitis, changes in the gut microbiota, and atrophy or degeneration of muscle fibers. The project “MISS: Microbiome Induced Space Suit” was presented at the Giant Jamboree of the International Genetically Engineered Machine Competition 2021, with the aim to investigate the ability of the novel microbiota-mediated approach to enhance human resistance to ionizing radiation. The key innovative part of the project was the idea to create a novel radioprotector delivery mechanism based on human gut microbiota with the function of outer membrane vesicles (OMVs) secretion. The project concept proposed the feasibility of genetically modifying the human microbiota in situ through the delivery of genetic constructs to the host’s crypts using silicon nanoparticles with chemically modified surfaces. In this perspective, we discuss the advances in modifying microbiota-mediated secretory activity as a promising approach for radioprotection and as an alternative to hormone therapy and other health conditions that currently require continuous drug administration. Future clinical trials of in situ methods to genetic engineering the crypt microbiota may pave the way for indirect regulation of human cells.

The current treatment of radiation-induced skin wounds utilizes mainly conventional therapies, including topical steroids, creams, ointments, and hydrogel dressings, which do not take into account the immunologic changes that occur in the skin after radiation exposure. Therefore, it is relevant to consider alternative therapies and their impact on changes in the immune landscape of the skin. The aim of this study was to investigate the effect of allogeneic minimally manipulated keratinocytes and fibroblasts on rat skin repair and the development of immune responses. We found that the use of cell therapy compared to treatment with syntazone ointment and no treatment resulted in faster healing and a reduction in the size of radiation-induced skin wounds, area of inflammation, and edema. Additionally, in the group receiving the cell therapy application, there was an observed increase in the number of mast cells (MCs), activation of MC interaction with M2 macrophages, a reduction in the direct contact of MCs with the vascular bed, an increase in the content of collagen fibers due to the intensification of collagen fibrillogenesis, and a restoration of their histotopographic organization. Thus, the positive effect of cell therapy based on allogeneic minimally manipulated keratinocytes and fibroblasts on skin regeneration indicated that it can be used in clinical practice to improve the effectiveness of rehabilitation after radiation therapy.

Articular cartilage, a crucial component of joint structure, ensures smooth articulation and efficient load distribution within the joint. However, its integrity is compromised in various pathological conditions, such as osteoarthritis, leading to significant alterations in its structure and function. This process was significantly correlated with Extracellular Matrix (ECM) degradation, loss of collagen type II, and increased expression of matrix metalloproteinases (MMPs), particularly MMP-13. The ability of chondrocytes to invade into the ECM in pathologically altered tissue leads to cartilage repair and regeneration, and becomes the basis of chondrocyte cell therapy. Furthermore, the altered mechanical properties of the ECM in diseased cartilage, alongside the upregulation of chemotactic factors, contribute to the enhanced migratory behavior of chondrocytes. Interestingly, chondrocytes invading the ECM displayed signs of phenotypic changes, such as increased proliferation and expression of markers associated with chondrocytes' intrinsic genetic properties. The invasion of chondrocytes into the ECM is a response to cartilage damage, possibly driven by an attempt to repair the degraded ECM, and varies in chondrocytes from different sources, i.e., articular cartilage or nasal septum. Nasal chondrocytes highlight the increase of ACAN, SOX9, N-cadherin, COL2A expression and decrease of IL1B, CXCL8, and MMPs gene family expression, which could relate to their unique phenotype properties. However, this response may paradoxically contribute to the progression of cartilage pathology by disrupting the tissue architecture and promoting further degeneration. Our review highlights the endogenous genetic properties of nasal chondrocytes to invade and repair damaged cartilage, offering promising avenues for cartilage repair and regeneration.

Objective: Traditional cell-based radiobiological methods are inadequate for assessing the toxicity of ionizing radiation exposure in relation to the microstructure of the extracellular matrix. Organotypic tissue slices preserve the spatial organization observed in vivo, making the tissue easily accessible for visualization and staining. This study aims to explore the use of fluorescence microscopy of physiologically compatible 3D tissue cultures to assess the effects of ionizing radiation. Methods: Organotypic tissue slices were obtained by vibratome, and their mechanical properties were studied. Slices were exposed by two ionizing radiation sources; electron beams (80 Gy and 4 Gy), and soft gamma irradiation (80 Gy and 4 Gy). Two tissue culture protocols were used: the standard (37°C), and hypothermic (30°C) conditions. A qualitative analysis of cell viability in organotypic tissue slices was performed using fluorescent dyes and standard laser confocal microscopy. Results: Biological dosimetry is represented by differentially stained 200-µm thick organotypic tissue sections related to living and dead cells and cell metabolic activity Conclusion: Our results underscore the ability of fluorescence laser scanning confocal microscopy to rapidly assess the radiobiological effects of ionizing radiation in vitro on 3D organotypic tissue slices.

In this study, the optimal engraving parameters were determined through the analysis of scanning electron microscopy (SEM) data, as follows: a laser power density of 5.5 × 10⁵ W/cm², an irradiation rate of 0.1 mm/s, a well radius of 60 μm, a distance between well centers of 200 μm, and a number of passes for each well of 20. After 1 week of in vitro cultivation, chondrocytes were located on the surface of the scaffolds, in the sockets and lacunae of decellularized cartilage. When implanted into animals, both cellular and acellular scaffolds were able to support cartilage in-growth and complete regeneration of the defect without clear boundaries with normal tissue. Nevertheless, the scaffolds populated with cells exhibited superior biocompatibility and were not subject to rejection, in contrast to cell-free constructs.