Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability.

Disruption of redox homeostasis profoundly affects cellular metabolism and activities. While oxidative stress is extensively studied in cancer therapies, research on reductive stress remains in its infancy. Molecular hydrogen (H), a well-known antioxidant, holds significant potential to induce reductive stress due to its strong antioxidative properties, making it a promising candidate for cancer therapy.

Molecular Deconvolution of Bone Marrow Adipose Tissue Interactions with Malignant Hematopoiesis: Potential for New Therapy Development.

Purpose Of Review: Along with a strong impact on skeletal integrity, bone marrow adipose tissue (BMAT) is an important modulator of the adult hematopoietic system. This review will summarize the current knowledge on the causal relationship between bone marrow (BM) adipogenesis and the development and progression of hematologic malignancies.

Recent Findings: BM adipocytes (BMAds) support a number of processes promoting oncogenesis, including the evolution of clonal hematopoiesis, malignant cell survival, proliferation, angiogenesis, and chemoresistance.

Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development.

Among multiple hemostasis components, platelets hyperactivity plays major roles in cancer progression by providing surface and internal components for intercellular crosstalk as well as by behaving like immune cells. Since platelets participate and regulate immunity in homeostatic and disease states, we assumed that revealing platelets profile might help in conceiving novel anti-cancer immune-based strategies. The goal of this review is to compile and discuss the most recent reports on the nature of cancer-associated platelets and their interference with immunotherapy.

The Role of Doxycycline and IL-17 in Regenerative Potential of Periodontal Ligament Stem Cells: Implications in Periodontitis.

Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism.

Targeting Stress Erythropoiesis Pathways in Cancer.

Cancer-related anemia (CRA) is a common multifactorial disorder that adversely affects the quality of life and overall prognosis in patients with cancer. Safety concerns associated with the most common CRA treatment options, including intravenous iron therapy and erythropoietic-stimulating agents, have often resulted in no or suboptimal anemia management for many cancer patients. Chronic anemia creates a vital need to restore normal erythropoietic output and therefore activates the mechanisms of stress erythropoiesis (SE).

A Single-Cell Raman Spectroscopy Analysis of Bone Marrow Mesenchymal Stem/Stromal Cells to Identify Inter-Individual Diversity.

The heterogeneity of stem cells represents the main challenge in regenerative medicine development. This issue is particularly pronounced when it comes to the use of primary mesenchymal stem/stromal cells (MSCs) due to a lack of identification markers. Considering the need for additional approaches in MSCs characterization, we applied Raman spectroscopy to investigate inter-individual differences between bone marrow MSCs (BM-MSCs).

Dental mesenchymal stromal/stem cells in different microenvironments- implications in regenerative therapy.

Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration.

Tumorigenic Aspects of MSC Senescence-Implication in Cancer Development and Therapy.

As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered to be the root of many diseases of the elderly, as infections, autoimmune and chronic inflammatory diseases, degenerative diseases, and cancer.

Modulating stemness of mesenchymal stem cells from exfoliated deciduous and permanent teeth by IL-17 and bFGF.

Mesenchymal stem cells (MSCs) have been identified within dental pulp tissues of exfoliated deciduous (SHEDs) and permanent (DPSCs) teeth. Although differences in their proliferative and differentiation properties were revealed, variability in SHEDs and DPSCs responsiveness to growth factors and cytokines have not been studied before. Here, we investigated the influence of interleukin-17 (IL-17) and basic fibroblast growth factor (bFGF) on stemness features of SHEDs and DPSCs by analyzing their proliferation, clonogenicity, cell cycle progression, pluripotency markers expression and differentiation after 7-day treatment.

Inflammatory niche: Mesenchymal stromal cell priming by soluble mediators.

Mesenchymal stromal/stem cells (MSCs) are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages. They play a critical role in tissue homeostasis and wound healing, as well as in regulating the inflammatory microenvironment through interactions with immune cells. Hence, MSCs have garnered great attention as promising candidates for tissue regeneration and cell therapy.

Specificity of 3D MSC Spheroids Microenvironment: Impact on MSC Behavior and Properties.

Mesenchymal stem cells (MSC) have been considered the promising candidates for the regenerative and personalized medicine due to their self-renewal potential, multilineage differentiation and immunomodulatory capacity. Although these properties have encouraged profound MSC studies in recent years, the majority of research has been based on standard 2D culture utilization. The opportunity to resemble in vivo characteristics of cells native niche has been provided by implementation of 3D culturing models such as MSC spheroid formation assesed through cells self-assembling.

IL-33 guides osteogenesis and increases proliferation and pluripotency marker expression in dental stem cells.

Objectives: Soluble IL-33 (interleukin (IL)-1-like cytokine) acts as endogenous alarm signal (alarmin). Since alarmins, besides activating immune system, act to restore tissue homeostasis, we investigated whether IL-33 exerts beneficial effects on oral stem cell pull.

Materials And Methods: Clonogenicity, proliferation, differentiation and senescence of stem cells derived from human periodontal ligament (PDLSCs) and dental pulp (DPSCs) were determined after in vitro exposure to IL-33.

Adipoinductive effect of extracellular matrix involves cytoskeleton changes and SIRT1 activity in adipose tissue stem/stromal cells.

Adipose tissue (AT) homeostasis and expansion are dependent on complex crosstalk between resident adipose stromal/stem cells (ASCs) and AT extracellular matrix (ECM). Although adipose tissue ECM (atECM) is one of the key players in the stem cell niche, data on bidirectional interaction of ASCs and atECM are still scarce. Here, we investigated how atECM guides ASCs' differentiation.

Mesenchymal stromal cell engagement in cancer cell epithelial to mesenchymal transition.

Due to coexistence of stromal and epithelial tumor cells, their dynamic interactions have been widely recognized as significant cellular components to the tumor tissue integrity. Initiation and outcome of epithelial to mesenchymal transition (EMT) in tumor cells are dependent on their interaction with adjacent or recruited mesenchymal stromal cells (MSCs). A plethora of mechanisms are involved in MSCs-controlled employment of the developmental processes of EMT that contribute to loss of epithelial cell phenotype and acquisition of stemness, invasiveness and chemoresistance of tumor cells.

Metabolic Plasticity of Stem Cells and Macrophages in Cancer.

In addition to providing essential molecules for the overall function of cells, metabolism plays an important role in cell fate and can be affected by microenvironmental stimuli as well as cellular interactions. As a specific niche, tumor microenvironment (TME), consisting of different cell types including stromal/stem cells and immune cells, is characterized by distinct metabolic properties. This review will be focused on the metabolic plasticity of mesenchymal stromal/stem cells (MSC) and macrophages in TME, as well as on how the metabolic state of cancer stem cells (CSC), as key drivers of oncogenesis, affects their generation and persistence.

Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation.

Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting.

Inflammatory cytokines prime adipose tissue mesenchymal stem cells to enhance malignancy of MCF-7 breast cancer cells via transforming growth factor-β1.

Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs-affected tumor development is not understood. We found that interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro.

The inhibition of periodontal ligament stem cells osteogenic differentiation by IL-17 is mediated via MAPKs.

Periodontal disease (PD), a degenerative bacterially induced disease of periodontium, can lead to bone resorption and teeth loss. Development of PD includes a strong inflammatory reaction, which involves multiple immune cells and their secreting factors including interleukin-17 (IL-17), which is not only an important modulator of immune and hematopoietic responses but also affects bone metabolism. In the present study we aimed to determine whether IL-17 affects the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) by investigating its ability to modulate osteogenic differentiation of these cells in vitro along with associated signaling pathways.

Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia.

Purpose: We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene.

Methods: The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34(+)cells/μl in peripheral blood.

Mesenchymal stem cells of different origin: Comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression.

Aims: In vitro expansion changes replication and differentiation capacity of mesenchymal stem cells (MSCs), increasing challenges and risks, while limiting the sufficient number of MSCs required for cytotherapy. Here, we characterized and compared proliferation, differentiation, telomere length and pluripotency marker expression in MSCs of various origins.

Main Methods: Immunophenotyping, proliferation and differentiation assays were performed.