Meat production and ethical concerns related to animal welfare have led to an increase in research into the creation of conventional meat. These technologies rely on the isolation, multiplication, and controlled differentiation of animal cells, which can potentially reduce negative environmental impact while maintaining comparable nutritional and sensory properties. The aim of this study is to comprehensively analyze and compare selected cell types used in the production of cultured meat, such as fibroblasts, satellite cells, adipocytes, and pluripotent cells: embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). It is important to consider the proliferative capacity, differentiation potential, suitability in scalable bioprocessing systems, and their impact on the structure and sensory properties of muscle tissue. This analysis demonstrates that no single cell type can fully replicate the complex structure of native muscle tissue. Satellite cells are responsible for the formation of muscle fibers, fibroblasts provide support through the synthesis of the extracellular matrix, and adipocytes contribute to the flavor and juiciness of the final product. Pluripotent cells differentiate into all of cell lineages, but their use is associated with regulatory and ethical considerations. This work also addresses key aspects of bioprocess engineering, such as scalability, culture conditions, and the importance of 3D cell culture and cell co-cultures in restoring tissue structure. Furthermore, regulatory, ethical, and economic issues affecting the feasibility of implementing the technology for industrial production are considered. In summary, the data presented indicate that the development of cultured meat requires an integrated approach combining appropriate cell selection, process optimization, and compliance with regulatory and ethical requirements.

Angiogenesis, the formation of new blood vessels from existing vasculature, is regulated by a balance between pro- and anti-angiogenic factors. In adults, this process typically occurs in response to inflammation, wound healing, and neoplastic growth. Uniquely, the female reproductive system undergoes cyclical and repetitive angiogenesis with folliculogenesis, decidualization, implantation, and embryo development throughout the reproductive cycle. Ovarian angiogenesis involves a coordinated network of signaling pathways and molecular factors. Vascular endothelial growth factor (VEGF) is the primary driver of this process, supported by other regulators such as fibroblast growth factor (FGF) and hypoxia-inducible factor (HIF). Understanding the molecular mechanisms that govern ovarian angiogenesis is essential for developing new diagnostic and therapeutic approaches in reproductive medicine. Vascular dysfunction and impaired angiogenesis are key contributors to various ovarian disorders and infertility, including polycystic ovary syndrome (PCOS). Therefore, in-depth studies of ovarian vascularization are crucial for identifying the pathophysiology of these conditions and guiding the development of effective treatments. Advancing knowledge in this area holds significant potential for innovation in both medicine and biotechnology.

Myocardial dysfunction, characterized by impaired cardiac muscle function, arises from diverse etiologies, including coronary artery disease, myocardial infarction, cardiomyopathies, hypertension, and valvular heart disease. Recent advancements have highlighted the roles of exosomes and non-coding RNAs in the pathophysiology of myocardial dysfunction. Exosomes are small extracellular vesicles released by cardiac and other cells that facilitate intercellular communication through their molecular cargo, including ncRNAs. ncRNAs are known to play critical roles in gene regulation through diverse mechanisms, impacting oxidative stress, fibrosis, and other factors associated with myocardial dysfunction. Dysregulation of these molecules correlates with disease progression, presenting opportunities for therapeutic interventions. This review explores the mechanistic interplay between exosomes and ncRNAs, underscoring their potential as biomarkers and therapeutic agents in myocardial dysfunction. Emerging evidence supports the use of engineered exosomes and modified ncRNAs to enhance cardiac repair by targeting signaling pathways associated with fibrosis, apoptosis, and angiogenesis. Despite promising preclinical results, delivery, stability, and immunogenicity challenges remain. Further research is needed to optimize clinical translation. Understanding these intricate mechanisms may drive the development of innovative strategies for diagnosing and treating myocardial dysfunction, ultimately improving patient outcomes.

Urine-derived stem cells (USCs) exhibit self-renewal, differentiating, and immunomodulatory properties, making them a valuable alternative to other stem cells, with wide potential in regenerative medicine. USCs exhibit a favorable immune profile through a presence of HLA-ABC and the absence of HLA-DR, which reduces the risk of transplant rejection. Specific importance has been emphasized on mitochondria. Crucial for endothelial and cardiovascular research is specificity of USCs mitochondria, which present young cell phenotype with high metabolic activity. It not only provides low oxidative stress level of the cells, but also exhibit anti-inflammatory influence on surrounding environment. Secretory activity of USCs can regulate apoptosis, angiogenesis, and inflammation, also activating signaling pathways such as NF-κB, STAT3, and Akt in recipient cells. Due to the acellular activity, USCs-Exos contain miRNAs involved in promoting angiogenesis, reducing fibrosis, and regulating apoptosis such as miR-16, miR-216, miR-26a, miR-146a and miR-140. Additionally, USCs can be reprogrammed into induced pluripotent stem cells (iPSCs). This expands opportunities for disease modeling, developing personalized therapies and reconstructions. However, there are still many limitations and clinical challenges, like cell isolation and its characterization, or urinary tract ailments which may impact the cells physiology. Still, USCs and their derivatives are promising tools in modern regenerative medicine, especially in endothelial and cardiovascular tissues. However, further research is needed to optimize their clinical applications and face the challenges.

As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with agerelated diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.

Biomimetic scaffolds imitate native tissue and can take a multidimensional form. They are biocompatible and can influence cellular metabolism, making them attractive bioengineering platforms. The use of biomimetic scaffolds adds complexity to traditional cell cultivation methods. The most commonly used technique involves cultivating cells on a flat surface in a two-dimensional format due to its simplicity. A three-dimensional (3D) format can provide a microenvironment for surrounding cells. There are two main techniques for obtaining 3D structures based on the presence of scaffolding. Scaffold-free techniques consist of spheroid technologies. Meanwhile, scaffold techniques contain organoids and all constructs that use various types of scaffolds, ranging from decellularized extracellular matrix (dECM) through hydrogels that are one of the most extensively studied forms of potential scaffolds for 3D culture up to 4D bioprinted biomaterials. 3D bioprinting is one of the most important techniques used to create biomimetic scaffolds. The versatility of this technique allows the use of many different types of inks, mainly hydrogels, as well as cells and inorganic substances. Increasing amounts of data provide evidence of vast potential of biomimetic scaffolds usage in tissue engineering and personalized medicine, with the main area of potential application being the regeneration of skin and musculoskeletal systems. Recent papers also indicate increasing amounts of in vivo tests of products based on biomimetic scaffolds, which further strengthen the importance of this branch of tissue engineering and emphasize the need for extensive research to provide safe for humansbiomimetic tissues and organs. In this review article, we provide a review of the recent advancements in the field of biomimetic scaffolds preceded by an overview of cell culture technologies that led to the development of biomimetic scaffold techniques as the most complex type of cell culture.

Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic.

Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.

A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. Abdominal aortic aneurysm (AAA) is a major pathological condition because it affects approximately 8% of elderly men and 1.5% of elderly women. The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases. The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes.

Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.

The oviduct provides an optimal environment for the final preparation, transport, and survival of gametes, the fertilization process, and early embryonic development. Most of the studies on reproduction are based on in vitro cell culture models because of the cell’s accessibility. It creates opportunities to explore the complexity of directly linked processes between cells. Previous studies showed a significant expression of genes responsible for cell differentiation, maturation, and development during long-term porcine oviduct epithelial cells (POECs) in vitro culture. This study aimed at establishing the transcriptomic profile and comprehensive characteristics of porcine oviduct epithelial cell in vitro cultures, to compare changes in gene expression over time and deliver information about the expression pattern of genes highlighted in specific GO groups. The oviduct cells were collected after 7, 15, and 30 days of in vitro cultivation. The transcriptomic profile of gene expression was compared to the control group (cells collected after the first day). The expression of COL1A2 and LOX was enhanced, while FGFBP1, SERPINB2, and OVGP1 were downregulated at all selected intervals of cell culture in comparison to the 24-h control (p-value < 0.05). Adding new detailed information to the reproductive biology field about the diversified transcriptome profile in POECs may create new future possibilities in infertility treatments, including assisted reproductive technique (ART) programmes, and may be a valuable tool to investigate the potential role of oviduct cells in post-ovulation events.

Objective: Inflammation fl ammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for patients with CVD, reducing the severity of the CVD-related symptoms and swelling but also reducing inflammation fl ammation and protecting endothelial cells. In this research, the effects of the serum obtained from patients with CVD before and after sulodexide treatment were evaluated for in vivo and in vitro inflammatory fl ammatory markers and endothelial cell function. Methods: Inflammatory fl ammatory markers (IL-6, matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], and von Willebrand factor [vWF]) from the incompetent great saphenous veins (GSVs) and from the systemic venous circulation were studied in 10 patients with CVD (C2s) before and after 2 months of sulodexide (2 x 500 lipasemic units/d) therapy. Serum obtained from the vein blood before and after sulodexide treatment was evaluated for in vitro cultured human umbilical vein endothelial cell function. Results: The serum collected from lower leg incompetent GSVs had significantly fi cantly elevated levels of VCAM-1 (+29%, + 29%, P < . 001) compared with the serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, + 17%, P < . 01), as well as increased markers of senescence (prolongation of population doubling time, b-galactosidase activity, and expression of p21 and p53 genes). CVD serum-induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1, and vWF synthesis. The overall proinflammatory fl ammatory effect on endothelial cells by the serum collected from the incompetent GSVs was stronger as compared with the serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory fl ammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory fl ammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory fl ammatory parameters in both lower limb incompetent vein and systemic blood. Conclusions: In patients with CVD, there are significant fi cant differences between circulating inflammatory fl ammatory markers analyzed from the lower leg incompetent GSV segments compared with the systemic circulation, indicating a higher inflam- fl am- matory condition in CVD. Treatment with sulodexide reduces the proinflammatory fl ammatory and endothelial cell activation properties of the serum from patients with CVD. (J Vasc Surg Venous Lymphat Disord 2024;12:101941.) Clinical Relevance: The study documented the significant fi cant proinflammatory fl ammatory human vascular endothelial cell activation when exposed to the serum collected from the varicose veins as compared with the serum from the systemic circulation in patients with chronic venous disease (CVD). The inflammatory fl ammatory marker expression, endothelial dysfunction, and endothelial cell senescence transformation can be successfully controlled and downregulated by patients' exposure to the glycosaminoglycan (sulodexide) treatment. Further studies are needed to confirm fi rm if glycosaminoglycan application can prevent further CVD clinical progression due to potential CVD-related pathological processes' modulation and their downregulation.

Small extracellular vesicles (sEVs) are a type of membranous vesicles that can be released by cells into the extracellular space. The relationship between sEVs and non-coding RNAs (ncRNAs) is highly intricate and interdependent. This symbiotic relationship plays a pivotal role in facilitating intercellular communication and holds profound implications for a myriad of biological processes. The concept of sEVs and their ncRNA cargo as a "Trojan Horse" highlights their remarkable capacity to traverse biological barriers and surreptitiously deliver their cargo to target cells, evading detection by the host-immune system. Accumulating evidence suggests that sEVs may be harnessed as carriers to ferry therapeutic ncRNAs capable of selectively silencing disease-driving genes, particularly in conditions such as cancer. This approach presents several advantages over conventional drug delivery methods, opening up new possibilities for targeted therapy and improved treatment outcomes. However, the utilization of sEVs and ncRNAs as therapeutic agents raises valid concerns regarding the possibility of unforeseen consequences and unintended impacts that may emerge from their application. It is important to consider the fundamental attributes of sEVs and ncRNAs, including by an in-depth analysis of the practical and clinical potentials of exosomes, serving as a representative model for sEVs encapsulating ncRNAs.

Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.

Heart failure remains a major cause of death worldwide. There is a need to establish new management options as current treatment is frequently suboptimal. Clinical approaches based on autologous stem cell transplant is potentially a good alternative. The heart was long considered an organ unable to regenerate and renew. However, several reports imply that it may possess modest intrinsic regenerative potential. To allow for detailed characterization of cell cultures, whole transcriptome profiling was performed after 0, 7, 15, and 30 days of in vitro cell cultures (IVC) from the right atrial appendage and right atrial wall utilizing microarray technology. In total, 4239 differentially expressed genes (DEGs) with ratio > abs |2| and adjusted p-value ≤ 0.05 for the right atrial wall and 4662 DEGs for the right atrial appendage were identified. It was shown that a subset of DEGs, which have demonstrated some regulation of expression levels with the duration of the cell culture, were enriched in the following GO BP (Gene Ontology Biological Process) terms: "stem cell population maintenance" and "stem cell proliferation". The results were validated by RT-qPCR. The establishment and detailed characterization of in vitro culture of myocardial cells may be important for future applications of these cells in heart regeneration processes.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers-CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton's jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.

It is now widely recognized that mesenchymal stem cells (MSCs) possess the capacity to differentiate into a wide array of cell types. Numerous studies have identified the role of lncRNA in the regulation of MSC differentiation. It is important to elucidate the role and interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of signalling pathways that govern MSC function. Furthermore, miRNAs and lncRNAs are important clinical for innovative strategies aimed at addressing a wide spectrum of existing and emerging disease. Hence it is important to consider their impact on MSC function and differentiation. Examining the data available in public databases, we have collected the literature containing the latest discoveries pertaining to human stem cells and their potential in both fundamental research and clinical applications. Furthermore, we have compiled completed clinical studies that revolve around the application of MSCs, shedding light on the opportunities presented by harnessing the regulatory potential of miRNAs and lncRNAs. This exploration of the therapeutic possibilities offered by miRNAs and lncRNAs within MSCs unveils exciting prospects for the development of precision therapies and personalized treatment approaches. Ultimately, these advancements promise to augment the efficacy of regenerative strategies and produce positive outcomes for patients. As research in this field continues to evolve, it is imperative to explore and exploit the vast potential of miRNAs and lncRNAs as therapeutic agents. The findings provide a solid basis for ongoing investigations, fuelling the quest to fully unlock the regenerative potential of MSCs.

Supplementary Figures S1-S2 from ABCC2 (MRP2, cMOAT) Can Be Localized in the Nuclear Membrane of Ovarian Carcinomas and Correlates with Resistance to Cisplatin and Clinical Outcome

In vitro meat production presents a potential viable alternative for meat consumption, which could provide the consumer with a product indistinguishable from the original, with very similar nutritional and culinary values. Indeed, the alternative products currently accessible often lack comparable nutritional value or culinary attributes to their animal-derived counterparts. This creates challenges for their global acceptance, particularly in countries where meat consumption holds cultural significance. However, while cultured meat research has been progressing rapidly in recent years, some significant obstacles still need to be overcome before its possible commercialization. Hence, this review summarizes the most current knowledge regarding the history of cultured meat, the currently used cell sources and methods used for the purpose of in vitro meat production, with particular focus on the role of bioreactors, scaffolds and microcarriers in overcoming the current obstacles. The authors put the potential microcarrier and scaffold-based solutions in a context, discussing the ways in which they can impact the way forward for the technology, including the use of considering the potential practical and societal barriers to implementing it as a viable food source worldwide.

Long non-coding RNAs (lncRNAs) are involved the progression of cancerous and non-cancerous disorders via different mechanism. FTX (five prime to xist) is an evolutionarily conserved lncRNA that is located upstream of XIST and regulates its expression. FTX participates in progression of various malignancy including gastric cancer, glioma, ovarian cancer, pancreatic cancer, and retinoblastoma. Also, FTX can be involved in the pathogenesis of non-cancerous disorders such as endometriosis and stroke. FTX acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-186, miR-200a-3p, miR-215-3p, and miR-153-3p to regulate the expression of their downstream target. FTX by targeting various signaling pathways including Wnt/β-catenin, PI3K/Akt, SOX4, PDK1/PKB/GSK-3β, TGF-β1, FOXA2, and PPARγ regulate molecular mechanism involved in various disorders. Dysregulation of FTX is associated with an increased risk of various disorders. Therefore, FTX and its downstream targets may be suitable biomarkers for the diagnosis and treatment of human malignancies. In this review, we summarized the emerging roles of FTX in human cancerous and non-cancerous cells.