Expert Revision of Key Elements for Clinical-Grade Production and Qualification of Perinatal Derivatives.

Perinatal derivatives have been proposed as adjunct therapeutic strategies or innovative treatments. Undoubtedly, perinatal derivatives can offer the opportunity and source material to isolate multipotent stem cells, but both maternal- and fetal-derived tissues can be processed and transformed into engineered tissues or advanced biomedical devices, whose potential remains to be fully elucidated. Promising preclinical and clinical results collected so far clearly foresee an escalation of such novel treatments.

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day.

Effects of human placenta cryopreservation on molecular characteristics of placental mesenchymal stromal cells.

Cryopreservation of placenta tissue for long-term storage provides the opportunity in the future to isolate mesenchymal stromal cells that could be used for cell therapy and regenerative medicine. Despite being widely used, the established cryopreservation protocols for freezing and thawing still raise concerns about their impact on molecular characteristics, such as epigenetic regulation. In our study, we compared the characteristics of human placental mesenchymal stromal cells (hPMSCs) isolated from fresh (native) and cryopreserved (cryo) placenta tissue.

Dynamic changes in radiological parameters, immune cells, selected miRNAs, and cytokine levels in peripheral blood of patients with severe COVID‑19.

The present study aimed to investigate the dynamic changes in peripheral blood leucocyte subpopulations, cytokine and miRNA levels, and changes in computed tomography (CT) scores in patients with severe coronavirus disease 2019 (COVID-19) (n=14) and age-matched non-COVID-19 volunteers (n=17), which were included as a reference control group. All data were collected on the day of patient admission (day 0) and on the 7th, 14th and 28th days of follow-up while CT of the lungs was performed on weeks 2, 8, 24 and 48. On day 0, lymphopenia and leucopenia were detected in most patients with COVID-19, as well as an increase in the percentage of banded neutrophils, B cells, and CD4 Treg cells, and a decrease in the content of PD-1 T cells, classical, plasmacytoid, and regulatory dendritic cells.

Expert Consideration on Regulatory Aspects for Perinatal Derivatives in Clinical Settings.

Perinatal derivatives (PnD) are drawing growing interest among the scientific community as an unrestricted source of multipotent stem cells, secretome, and biological matrices. They are useful for the treatment of diseases that currently have limited or no effective therapeutic options, but they require the development of regenerative approaches. With this development, the question of regulation of donation, processing, and distribution has therefore become more important.

Treatment of Acute Respiratory Distress Syndrome Caused by COVID-19 with Human Umbilical Cord Mesenchymal Stem Cells.

This study aimed to identify the impact of mesenchymal stem cell transplantation on the safety and clinical outcomes of patients with severe COVID-19. This research focused on how lung functional status, miRNA, and cytokine levels changed following mesenchymal stem cell transplantation in patients with severe COVID-19 pneumonia and their correlation with fibrotic changes in the lung. This study involved 15 patients following conventional anti-viral treatment (Control group) and 13 patients after three consecutive doses of combined treatment with MSC transplantation (MCS group).

Perinatal derivatives application: Identifying possibilities for clinical use.

Perinatal derivatives are drawing growing interest among the scientific community as an unrestricted source of multipotent stromal cells, stem cells, cellular soluble mediators, and biological matrices. They are useful for the treatment of diseases that currently have limited or no effective therapeutic options by means of developing regenerative approaches. In this paper, to generate a complete view of the state of the art, a comprehensive 10-years compilation of clinical-trial data with the common denominator of PnD usage has been discussed, including commercialized products.

High Proliferative Placenta-Derived Multipotent Cells Express Cytokeratin 7 at Low Level.

The purpose of this study was to investigate the immunophenotypes and gene expression profile of high proliferative placenta-derived multipotent cells (PDMCs) population at different stages of culture. We demonstrated that the colonies resulting from single cells were either positive or negative for CK7, whereas only PDMC clones with weak CK7 expression (CK7-clones) were highly proliferative. Interestingly, vimentin positive (Vim) placental stromal mesenchymal cells did not express CK7 , but double CK7Vim cells detection in tissue explants and explants outgrowth indicated CK7 inducible expression .

Morpho-Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells after Activation or Inhibition of Epidermal Growth Factor and Toll-Like Receptors or Treatment with DNA Intercalator Cisplatin.

This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control.

Transplantation of placenta-derived multipotent cells in rats with dimethylhydrazine-induced colon cancer decreases survival rate.

Transplantation of placenta-derived multipotent cells (PDMCs) is a promising treatment method for many diseases. However, the impact of PDMCs on colon cancer has not yet been studied. PDMCs were obtained from rat placentas by culturing tissue explants.

Placenta-derived multipotent cells have no effect on the size and number of DMH-induced colon tumors in rats.

Transplantation of placenta-derived multipotent cells (PDMCs) is a promising approach for cell therapy to treat inflammation-associated colon diseases. However, the effect of PDMCs on colon cancer cells remains unknown. The aim of the present study was to characterize PDMCs obtained from human (hPDMCs) and rat (rPDMCs) placentas and to evaluate their impact on colon cancer progression in rats.

Comparative Analysis of the Hematopoietic Progenitor Cells from Placenta, Cord Blood, and Fetal Liver, Based on Their Immunophenotype.

We have investigated the characteristics of human hematopoietic progenitor cells (HPCs) with the CD34(+)CD45(low)SSC(low) phenotype from full-term placental tissue (FTPT) as compared to cord blood (CB) and fetal liver (FL) cells. We demonstrated the presence of cell subpopulations at various stages of the differentiation with such immunophenotypes as CD34(+/low)CD45(low/-), CD34(++)CD45(low/-), CD34(+++)CD45(low/-), CD34(+/low)CD45(hi), and CD34(++)CD45(hi) in both first trimester placental tissue (FiTPT) and FTPT which implies their higher phenotypic heterogeneity compared to CB. HPCs of the FTPT origin expressed the CD90 antigen at a higher level compared to its expression by the CB HPCs and the CD133 antigen expression being at the same level in both cases.

[Effects of the umbilical blood stem cells in experimental injury of myocardium].

Morphological, functional signs of myocardium affection and tolerance to physical loading in animals with isoproterenol-induced affection of myocardium after transplantation of a nuclear-containing cells (NCC) of umbilical blood were analyzed in comparison with a natural course of the model. There was proved, that a transplantation of a NCC promotes acceleration of processes of regeneration and restoration of the damaged myocardium in experimental animals. There were estimated the changes in localization of the transplanted NCC in the zone of damage, and capacity of the peripheral blood NCC, while they were transplanted, using intravenous injection, to migrate into the damage zone.

[Perspectives of application of allogeneic multipotent mesenchymal stem cells for the adipose transplant protection from tissue resorption].

The detection of possibility differentiation towards adipogenic trend of the cells, which were obtained from adipose tissue, and their impact on the processes of adipose transplant resorption, in condition of its allogenic transplantation, have had constituted the objective of the investigation. Combined transplantation of adipose transplant and multipotent mesenchymal stem cells, obtained from allogenic adipose tissue, causes the destruction-inflammatory processes activation in the adipose transplant, as well as the adipocytes survival worsening in a meanwhile - a significant deficiency in the transplant mass.

[Transplantation of the adipose tissue enriched by allogenic mesenchymal multipotent stem cells in experimental conditions].

There was conducted experimental investigation with objective to study up the influence of transplantation of a native allogenic multipotent mesenchymal stem cells on the processes of implantation and functioning of heterotopically transplanted autologous adipose tissue. In a cellular-tissue graft, in which native allogenic mesenchymal stem cells were applied as a cellular component, there was observed a worsening of the adipocytes survival indices as well as activation of destructive and inflammatory processes.

[The role of some donor-host cell interactions in conditions of the regenerative process microenvironment].

The review is devoted to the analysis of experimental data about possible mechanisms of transdifferentiation or plasticity of tissue specific stem cells. Considerable attention is focused on the mechanisms and genetic consequences of fusion of different types of donor cells with the cells of recipient tissues which investigated on the models of cellular therapy of liver and heart diseases. The role of various kinds of cell contacts and their role in stem cells integration, reparation and regeneration of injured tissue and horizontal genes transfer are considered.

[Jasmonic acid and its participation in defence reactions of plant organism].

The main stages and inductors of biosynthesis of jasmonic acid and its derivatives, peculiarities of their content depending on the type of tissue, organ, plant age, mechanical irritation, injury and the impact of pathogens are considered. Data about use of mutant and transgenic plants with disturbed biosynthesis and perception of jasmonic acid for research ofjasmonate value in the induction of defense reactions are presented. Enzymes that are involved in the biosynthesis of jasmonic acid, synergistic (with abscisic acid, ethylene) and antagonistic (with salicylic acid) action of jasmonic acid with other phytohormones are described.