Targeted radionuclide therapy, known as molecular radiotherapy is a novel therapeutic module in cancer medicine. β-radiating radionuclides have definite impact on target cells via interference in cell cycle and particular signalings that can lead to tumor regression with minimal off-target effects on the surrounding tissues. Radionuclides play a remarkable role not only in apoptosis induction and cell cycle arrest, but also in the amelioration of other characteristics of cancer cells. Recently, application of novel β-radiating radionuclides in cancer therapy has been emerged as a promising therapeutic modality. Several investigations are ongoing to understand the underlying molecular mechanisms of β-radiating elements in cancer medicine. Based on the radiation dose, exposure time and type of the β-radiating element, different results could be achieved in cancer cells. It has been shown that β-radiating radioisotopes block cancer cell proliferation by inducing apoptosis and cell cycle arrest. However, physical characteristics of the β-radiating element (half-life, tissue penetration range, and maximum energy) and treatment protocol determine whether tumor cells undergo cell cycle arrest, apoptosis or both and to which extent. In this review, we highlighted novel therapeutic effects of β-radiating radionuclides on cancer cells, particularly apoptosis induction and cell cycle arrest.

Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates-spheroids-have become widely used model objects in the study of this phenomenon. existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. this discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation. Modern approaches to the rapidly evolving fields of regenerative medicine and tissue engineering are closely associated with the development and formation of tissue-engineered constructions, where cellular components play a crucial role 1-3. Monolayer cell culture is the most widely used approach to the growing and studying of cells in vitro. Nevertheless, 2D culture conditions cause cell flattening and remodeling of the cell's internal structure, which can eventually affect the gene expression 4. On the other hand, 3D cell culture better reflects the in vivo microenvironment both morphologically and physiologically. The extra dimension which 3D cell cultures have, compared to monolayers, helps to establish intercellular junctions, to reorganize the cytoskeleton, to polarize and to differentiate in conditions similar to native tissue conditions 5. Multicellular spheroids obtained under nonadhesive conditions represent one possible 3D cell culture system. There is a great deal of unexplored potential in spheroid-based research, as tissue engineering using spheroids is a relatively new field 6-8. Three-dimensional bioprinting of scaffold-based and scaffold-free tissue-engineered constructions is widely used for tissue substitution and modeling of organs-on-chips 9-12. Cell spheroids with prefabricated intercellular junctions and extracellular matrix provide a new promising type of bioinks suitable for processing by an

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Osteoarthritis (OA) affects over 250 million people worldwide and despite various existing treatment strategies still has no cure. It is a multifactorial disease characterized by cartilage loss and low-grade synovial inflammation. Focusing on these two targets together could be the key to developing currently missing disease-modifying OA drugs (DMOADs). This review aims to discuss the latest cell-free techniques applied in cartilage tissue regeneration, since they can provide a more controllable approach to inflammation management than the cell-based ones. Scaffolds, extracellular vesicles, and nanocarriers can be used to suppress inflammation, but they can also act as immunomodulatory agents. This is consistent with the latest tissue engineering paradigm, postulating a moderate, controllable inflammatory reaction to be beneficial for tissue remodeling and successful regeneration.

Background Recurrence in hepatocellular carcinoma (HCC) after conventional treatments is a big challenge. Despite the promising progress in advanced targeted therapies, HCC is the fourth leading cause of cancer death worldwide. Radionuclide therapy could be an effective targeted approach to address this concern. Rhenium-188 (188Re) is a β-emitting radionuclide that can be used in clinic for apoptosis induction and inhibit cell proliferation. Although adherent cell cultures are efficient and reliable, the lack of appropriate cell-cell and cell-ECM contact exists. It has been demonstrated that three-dimensional organotypic human cancer models are suitable alternatives. Methods Conventional adherent culture and 3D constructs of Huh7 or HepG2 hepatoma cell lines cultured on liver extracellular matrix (ECM) were treated by different doses of 188 Rhenium Perrhenate (188ReO4). To evaluate cell viability, live/dead assay carried out. The flow-cytometric assay, qRT-PCR, western bolting, colony formation assay, and immunofluorescence (IF) studies were performed to investigate the therapeutic effect of 188ReO4. Subsequently, the tumor formation ability of 188ReO4-treated Huh7 cells was evaluated in animal model. Results According to viability assay and live/dead staining, the number of dead cells in Huh7 and HepG2 lines were significantly increased compared to untreated control groups. Data obtained from Annexin/PI showed that Huh7 and HepG2 cells showed typical apoptotic changes after treatment with 188ReO4. Quantitative RT-PCR and western blotting data also supported that 188ReO4 treatment can induce apoptosis. Furthermore, cell cycle arrest observed in G2 phase after exposure to effective dose of 188ReO4 in Huh7 cells. Colony formation assay confirmed growth suppression in Huh7 and HepG2 cells post exposure. The IF also displayed proliferation inhibition in the 188ReO4 treated cells on 3D scaffolds of liver extracellular matrix (LEM). In 2D culture, PI3-AKT signaling pathway remained unchanged whereas, in the 3D condition it was activated. Treated Huh7 cells with effective dose of 188ReO4 lose their tumor formation ability in nude mice compare to the control group. Conclusion The results supported that 188ReO4 could induce apoptosis and cell cycle arrest and inhibit tumor formation capacity in HCC cells.

. Significance : The method of photobiomodulation (PBM) has been used in medicine for a long time to promote anti-inflammation and pain-resolving processes in different organs and tissues. PBM triggers numerous cellular pathways including stimulation of the mitochondrial respiratory chain, alteration of the cytoskeleton, cell death prevention, increasing proliferative activity, and directing cell differentiation. The most effective wavelengths for PBM are found within the optical window (750 to 1100 nm), in which light can permeate tissues and other water-containing structures to depths of up to a few cm. PBM already finds its applications in the developing fields of tissue engineering and regenerative medicine. However, the diversity of three-dimensional (3D) systems, irradiation sources, and protocols intricate the PBM applications. Aim: We aim to discuss the PBM and 3D tissue engineered constructs to define the fields of interest for PBM applications in tissue engineering. Approach : First, we provide a brief overview of PBM and the timeline of its development. Then, we discuss the optical properties of 3D cultivation systems and important points of light dosimetry. Finally, we analyze the cellular pathways induced by PBM and outcomes observed in various 3D tissue-engineered constructs: hydrogels, scaffolds, spheroids, cell sheets, bioprinted structures, and organoids. Results: Our summarized results demonstrate the great potential of PBM in the stimulation of the cell survival and viability in 3D conditions. The strategies to achieve different cell physiology states with particular PBM parameters are outlined. Conclusions: PBM has already proved itself as a convenient and effective tool to prevent drastic cellular events in the stress conditions. Because of the poor viability of cells in scaffolds and the convenience of PBM devices, 3D tissue engineering is a perspective field for PBM applications.

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