Throughout life, the cellular components of tissues and organs require timely renewal and repair following significant damage. This function is carried out by stem cells, which in adult organisms are regulated by a specialized microenvironment known as the stem cell niche. Dysfunction of the niche can lead to loss of tissue integrity and impaired function. However, it has been demonstrated that the stem cell niche is capable of partial recovery. A significant contribution to this process is made by multipotent mesenchymal stem/stromal cells (MSCs), which are found in various tissue-specific stem cell niches, where they participate in maintaining and repairing damaged niches, presumably through the secretion of a wide range of factors collectively referred to as the secretome, which are involved in regulating tissue repair and regeneration. The use of the cell secretome, particularly that of MSCs, as regenerative medicine products underlies an emerging field of cell therapy known as “cell-free cell therapy”.

Recently, the first regulatory clinical trial of an original biological drug, “MediReg”®, based on the secretome of human MSCs was initiated in the Russian Federation. Developed and manufactured at Lomonosov Moscow State University, this drug is intended to treat severe impairments of spermatogenesis by stimulating the recovery of the damaged spermatogonial stem cell niche. In this brief communication, using “MediReg”® as an example, we discuss the key aspects of the development and preclinical studies of biological drugs based on the secretome of human MSCs, as well as the prospects for their translation into clinical practice.

Regenerative medicine is an advanced field of biomedicine aimed at repairing damaged tissues and organs. Promising areas of research include the creation of artificial organs, the development of biomaterials and personalized medicine in the treatment of cardiovascular, neurodegenerative, oncological diseases, diabetes mellitus, and many others. Researchers face challenges related to immunological reactions, ethical issues, and technology scaling. Stem cells (SC) and their products, including small extracellular vesicles (sEV), are promising tools for the therapy of diseases that are currently difficult to treat with the existing approaches. Cell therapy based on mesenchymal, embryonic, neural, and induced pluripotent SC is a promising method for the treatment of neurodegenerative diseases, the prevalence of which is increasing due to an increase in life expectancy of the population. The interest in sEV is explained by the fact that the effect of sEV transplantation is comparable to that of maternal cells, and their small size gives them obvious advantages in distribution throughout the recipient’s body. This review provides experimental and clinical data on the use of SC and their products for the treatment of neurodegenerative diseases and their prevention.

T-cadherin (also known as cadherin 13, H-cadherin (heart), and CDH13) is a multifunctional protein that plays a key role in metabolism regulation, adipogenesis, and carcinogenesis. The review presents current perspectives on the structure and functions of T-cadherin, interaction with its well-known ligands (adiponectin, and low-density lipoproteins (LDL)). Special attention is given to analysing the role of T-cadherin in adipogenic differentiation of mesenchymal stromal/stem cells (MSCs), as well as its effects on lipid accumulation and the maintenance of metabolic homeostasis. It is suggested that T-cadherin may act as a sensor of metabolic signals, regulating the balance between adipogenesis and the activation of stem/progenitor cells, which is crucial for maintaining cellular homeostasis in adipose tissue.

In the context of oncological diseases, T-cadherin functions as a potential tumor suppressor. Loss of T-cadherin expression is a hallmark of many cancers, including breast, lung, and colorectal cancer. Reduced levels of T-cadherin are associated with hypermethylation of the CDH13 gene promoter or loss of heterozygosity in the CDH13 gene region. T-cadherin may also mediate the protective effects of adiponectin, which has oncosuppressive properties. Imbalances between adiponectin and LDL in obesity and metabolic syndrome may contribute to the development of oncological diseases. Thus, T-cadherin may mediate the link between obesity and carcinogenesis. Its ability to regulate adipogenesis and interact with ligands affecting overall metabolism, makes this protein a promising target for further research. Understanding the molecular mechanisms mediated by T-cadherin may open new avenues to treatment of obesity and related oncological diseases.

In this work, we studied how hormonal regulation of human adipose tissue stem cells changes during aging and how changes in hormonal regulation are associated with adipogenic differentiation of these cells. Postnatal adipose tissue stem cells — multipotent mesenchymal stromal cells (MSCs), were used as an object for studying hormonal regulation. We showed that both MSCs with induced replicative senescence and MSCs obtained from elderly donors have a reduced adipogenic potential. These cells have impaired mechanisms of regulation of adipogenic differentiation under noradrenaline and serotonin. The study of intracellular signaling cascades allowed us to establish that during senescence, MSCs exhibit reduced activation of both cAMP-dependent and phosphoinositide/calcium-dependent signaling cascades. Moreover, calcium responses to the addition of these hormones were delayed in time in MSCs with induced replicative aging. Thus, senescence leads to a decrease in the regulatory effect of hormones on the adipogenic differentiation of human MSCs.

The formation of a tissue equivalent based on injectable form of microdispersed scaffold — microparticles of decellularized porcine cartilage (DecCp) — seems to be a promising technology for repairing cartilage tissue defects. The aim of this work was to obtain and comparatively study a tissue-engineering construct (TEC) based on DecCp microparticles and mesenchymal stromal cells (MSCs) under static conditions and in perfusion bioreactor. Materials and methods. The decellularization process included freeze-thaw cycles (-196 °C...+37 °C), the use of surfactants (Triton X-100 and sodium dodecyl sulfate), as well as DNase treatment. The morphology of the surface and the nearest subsurface layer of the samples was studied using scanning electron microscopy. Each TEC consisted of 5×10⁵ MSCs and 5 mg DecCp. Results. It was found that, compared with static conditions, the cultivation of MSCs on DecCp microparticles in a perfusion bioreactor for 14 days allows increasing the proliferative activity of cells with subsequent chondrogenic differentiation, as evidenced by the ability of the cellular component of cartilage to synthesize extracellular matrix (ECM), characteristic of cartilage tissue, histochemical analysis of which revealed the presence of collagen and glycosaminoglycans (GAG). Conclusion. The possibility of forming cartilage TECs based on DecCp and MSCs under 3D cultivation conditions both under static conditions and in a perfusion bioreactor was shown. Cultivation of MSCs on DecCp under flow conditions at a rate of 0.5 ml/min contributed to an increase in cell proliferative activity compared with static conditions, and also supported the ability of cells to synthesize ECM, characteristic of cartilage tissue, histochemical analysis of which revealed the presence of total collagen and GAG, which may be evidence of chondrogenic differentiation of MSCs.