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Aging process is associated with numerous intrinsic and extrinsic factors that contribute to the adipose tissue accumulation, atherosclerosis, immune system failures, bone fragility, and cancer [...]
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Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various... more
Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various proinflammatory cytokines, including interleukin (IL)-17. Successful regeneration of damaged periodontal tissues depends on the proper functionality of periodontal ligament mesenchymal stem cells (PDLMSCs), especially the production of extracellular matrix proteases. We investigated the influence of IL-17 on ECM remodeling through modulation of urokinasetype plasminogen activator (uPA) and MMP2/MMP9 expression in human PDLMSCs at mRNA, protein and activity levels using by RT-PCR, Western blotting and zymography, respectively. Investigation of the involvement of MAPKs in these processes in PDLMSCs was determined by Western blotting, as well as by utilizing specific p38 and MEK1/2 inhibitors. Our results show that IL-17 activates MAPK signaling in PDLMSCs. Moreover...
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The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not... more
The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine—mainly in combination with various biomaterial matrices—has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MS...
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The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various... more
The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progeni...
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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,... more
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. Results indicated that IL‐17 and bFGF differently affected SHEDs and DPSCs proliferation and clonogenicity, since bFGF increased proliferative and clonogenic potential of both cell types, while IL‐17 similarly affected SHEDs, exerting no effects on adult counterparts DPSCs. In addition, both factors stimulated NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs showing diverse intracellular expression patterns dependent on MSCs type. As for the differentiation capacity, both factors displayed comparable effects on SHEDs and DPSCs, including stimulatory effect of IL‐17 on early osteogenesis in contrast to the strong inhibitory effect showed for bFGF, while having no impact on SHEDs and DPSCs chondrogenesis. Moreover, bFGF combined with IL‐17 reduced CD90 and stimulated CD73 expression on both types of MSCs, whereas each factor induced IL‐6 expression indicating its' role in IL‐17/bFGF‐modulated properties of SHEDs and DPSCs. All these data demonstrated that dental pulp MSCs from primary and permanent teeth exert intrinsic features, providing novel evidence on how IL‐17 and bFGF affect stem cell properties important for regeneration of dental pulp at different ages.
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Research Interests: Chemistry, Cell Biology, Medicine, LPS, Cell Differentiation, and 15 moreHumans, Immunomodulation, Adipogenesis, Cellular Physiology, Medical Physiology, Differentiation, Alkaline phosphatase, Mitogen Activated Protein Kinase, Myofibroblasts, Lipopolysaccharides, Chondrogenesis, Cell Proliferation, Cellular Microenvironment, Gene Expression Regulation, and Interleukin
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... more
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. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK...
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State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells... more
State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that ma...
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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... more
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. Our results revealed that IL-17 inhibited both the proliferation and migration of PDLSCs and decreased their osteogenic differentiation by activating ERK1,2 and JNK mitogen-activated protein kinases. Obtained data suggested that IL-17 might contribute to alveolar bone loss in PD.
Research Interests: Chemistry, Cell Biology, Stem Cell, Medicine, Signal Transduction, and 15 moreCell Differentiation, Humans, Periodontal Ligament, Mesenchymal Stem Cell, Haematopoiesis, Phenotype, Immune system, Adult, Osteogenic differentiation, Osteogenesis, Cell Proliferation, Bone Resorption, Biochemistry and cell biology, Interleukin, and periodontium
Research Interests: Biomarkers, Biology, Life Sciences, Medicine, Adipose tissue, and 15 moreCell line, Cell Differentiation, Mesenchymal stem cells, Humans, Pluripotency, Adipogenesis, Mesenchymal Stem Cell, Differentiation, Osteogenesis, Cell Proliferation, Ligaments, Blood cells, Mesenchymal Stromal Cells, Biochemistry and cell biology, and Pharmacology and pharmaceutical sciences
Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-βand ROS in tumorigenesis and cancer... more
Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-βand ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-βcan control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-βsignaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-βand ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation b...
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Natural products have been investigated for promising new leads in pharmaceutical development. The purpose of this study was to analyze the biological effect of GE132+Natural, a novel supplement consisting of 5 compounds: Resveratrol,... more
Natural products have been investigated for promising new leads in pharmaceutical development. The purpose of this study was to analyze the biological effect of GE132+Natural, a novel supplement consisting of 5 compounds: Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly. The antiproliferative activity of GE132+Natural was tested on 3 different human cancer cell lines: MCF7 (breast cancer cells), PC3 (prostate cancer cells), and SW480 (colon cancer cells), as well as on EA.hy 926 (normal human endothelial cell line). In addition, the cytotoxicity of GE132+- Natural on the proliferation of primary human mesenchymal stem cells isolated from dental pulp (DP=MSC), along with its in vitro impact on different peripheral blood parameters, was determined. The results revealed high antiproliferative activity of GE132+Natural on all tested cancer cell lines (PC3, MCF7 and SW480), as well as on the EA.hy 926 endothelial cell line in a dose-dependent manner. However, applie...
Research Interests: Chemistry, Breast Cancer, Medicine, Humans, Internal Medicine, and 15 moreEndothelial Cells, Female, Gynecology and Obstetrics, Male, Dietary Supplements, Mesenchymal Stem Cell, Colon cancer, Cancer Cell, Cell Proliferation, Antineoplastic Agents, Blood cells, Mesenchymal Stromal Cells, Breast Neoplasms, Colonic Neoplasms, and Drug combinations
Interleukin-17 is Th17 cell cytokine implicated in regulation of hematopoiesis and inflammation. Besides promoting granulopoiesis, we have previously shown that IL-17 also affects erythropoiesis stimulating the development of early... more
Interleukin-17 is Th17 cell cytokine implicated in regulation of hematopoiesis and inflammation. Besides promoting granulopoiesis, we have previously shown that IL-17 also affects erythropoiesis stimulating the development of early erythroid progenitors, BFU-E, but suppressing, at least partly via p38 MAPK, the growth of late stage erythroid progenitors, CFU-E. The aim of the present study was to investigate the involvement of other MAPKs, JNK and ERK1/2, as well as GATA transcription factors, in IL-17-mediated effects on murine bone marrow erythroid progenitors. Data obtained by use of specific MAPKs inhibitors indicated that MEK1/2-ERK1/2 MAPK signaling mediates IL-17-induced CFU-E inhibition, as well as that JNK and/or MEK1/2-ERK1/2 MAPKs activation underlies IL-17-induced stimulation of BFU-E growth. Furthermore, Western blot analyses demonstrated no effect on early hematopoiesis transcription factor, GATA-2, and enhanced expression level of erythroid-specific factor GATA-1 in m...
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Introduction. Mesenchymal stem cells (MSCs) are a promising tool for regenerative medicine, but due to the heterogeneity of their populations, different sources and isolation techniques, the characteristics defining MSCs are inconsistent.... more
Introduction. Mesenchymal stem cells (MSCs) are a promising tool for regenerative medicine, but due to the heterogeneity of their populations, different sources and isolation techniques, the characteristics defining MSCs are inconsistent. Objective. The aim of this study was to compare the characteristics of MSCs derived from two different human tissues: peripheral blood (PB-MSCs) and umbilical cord Wharton?s Jelly (UC-MSCs). Methods. The PB-MSC and UC-MSC were isolated by adherence to plastic after gradient-density separation or an explant culture method, respectively, and compared regarding their morphology, clonogenic efficiency, proliferating rates, immunophenotype and differentiation potential. Results. MSCs derived from both sources exhibit similar morphology, proliferation capacity and multilineage (osteogenic, chondrogenic, adipogenic and myogenic) differentiation potential. Differences were observed in the clonogenic capacity and the immunophenotype, since UC-MSCs showed hi...
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The aim of this study has been to elucidate how different oxygen levels impact the effects of Interleukin-17 (IL-17) on angiogenic properties of endothelial cells. Two endothelial cell lines, mouse MS-1 and human EA.hy 926, were grown in... more
The aim of this study has been to elucidate how different oxygen levels impact the effects of Interleukin-17 (IL-17) on angiogenic properties of endothelial cells. Two endothelial cell lines, mouse MS-1 and human EA.hy 926, were grown in 20% and 3% O2 and their angiogenic abilities analyzed after IL-17 treatment: proliferation, apoptosis, migration and tubulogenesis. Expression of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (Cox-2) was also measured. Considering EA.hy 926 cell line, hypoxia alone reduced proliferation, survival and migration, but not their ability to form tubules. When cultured at 20% O2 , IL-17 stimulated proliferation, migration and tubulogenesis, whereas a hypoxic environment did not affect their migration and proliferation, but increased their survival and tubulogenic properties. Expression of eNOS and Cox-2 increased by both IL-17 and hypoxia, as well as with their combination. With the MS-1 cell line hypoxia did not affect proliferation, survival, migration and tubule formation. At 20% O2 , IL-17 did not alter their proliferation,but inhibited migration and stimulated tubule formation. At 3% O2 , only the stimulating effect of IL-17 on tubulogenesis was evident. The constitutive expression of eNOS was unaffected by oxygen concentrations or IL-17 supplementation, whereas both IL-17 and hypoxia upregulated Cox-2 expression. Thus the effects of IL-17 on the angiogenic properties of endothelial cells depend on both the cell line used and the oxygen concentration.
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Research Interests: Biology, Cell Biology, Medicine, Signal Transduction, Mesenchymal stem cells, and 15 moreMice, Mouse, Animals, Male, Mesenchymal Stem Cell, Medical Physiology, bFGF, Fibroblast Growth Factor, IL, Signaling, Recombinant Proteins, Mesenchymal Stromal Cells, Interleukin, Basic Fibroblast Growth Factor, and Fibroblast growth factors
In the present study we have isolated and identified mesenchymal stem cells (MSCs) from the exfoliated deciduous teeth dental pulp (DP-MSCs), as plastic-adherent, spindle-shaped cells with a high proliferative potential. Immunophenotype... more
In the present study we have isolated and identified mesenchymal stem cells (MSCs) from the exfoliated deciduous teeth dental pulp (DP-MSCs), as plastic-adherent, spindle-shaped cells with a high proliferative potential. Immunophenotype analyses revealed that DP-MSCs were positive for mesenchymal cell markers (CD90, CD44, CD105, STRO-1, vimentin and ?-SMA), and negative for hematopoietic stem cell markers (CD11b, CD33, CD34, CD45, CD235a). DPMSCs were also capable of differentiating into adipogenic, chondrogenic, myogenic and osteogenic lineages, fulfilling the functional criterion for their characterization. These results demonstrate that DP-MSCs offer a valuable, readily accessible source to obtain and store adult stem cells for future use.
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Research Interests: Cancer, Biology, Cell Biology, Cancer Research, Medicine, and 15 moreAdipose tissue, Cell Differentiation, Mesenchymal stem cells, Humans, Female, Mesenchymal Stem Cell, Breast, CD, Immunophenotyping, Cell Proliferation, Mesenchymal Stromal Cells, Biochemistry and cell biology, Gene expression profiling, Breast Neoplasms, and coculture techniques
Research Interests: Cancer Research, Epithelial-Mesenchymal Transition, Signal Transduction, Adipose tissue, Humans, and 9 moreFemale, Mesenchymal Stem Cell, Neoplasm Invasiveness, Tumor necrosis factor-alpha, Transforming Growth Factor Beta, Mesenchymal Stromal Cells, Biochemistry and cell biology, Interferon gamma, and Breast Neoplasms
Research Interests: Chemistry, Medical Microbiology, Medicine, Bone Morphogenetic Proteins, Biological Sciences, and 14 moreCell line, Myoblast, Cell Differentiation, Mice, Animals, Physical sciences, Mitogen Activated Protein Kinase, IL, Muscle development, Osteogenesis, Cell Proliferation, Biochemistry and cell biology, Interleukin, and Myoblasts
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Interleukin-17 is Th17 cell cytokine implicated in regulation of hematopoiesis and inflammation. Besides promoting granulopoiesis, we have previously shown that IL-17 also affects erythropoiesis stimulating the development of early... more
Interleukin-17 is Th17 cell cytokine implicated in regulation of hematopoiesis and inflammation. Besides promoting granulopoiesis, we have previously shown that IL-17 also affects erythropoiesis stimulating the development of early erythroid progenitors, BFU-E, but suppressing, at least partly via p38 MAPK, the growth of late stage erythroid progenitors, CFU-E. The aim of the present study was to investigate the involvement of other MAPKs, JNK and ERK1/2, as well as GATA transcription factors, in IL-17-mediated effects on murine bone marrow erythroid progenitors. Data obtained by use of specific MAPKs inhibitors indicated that MEK1/2-ERK1/2 MAPK signaling mediates IL-17-induced CFU-E inhibition, as well as that JNK and/or MEK1/2-ERK1/2 MAPKs activation underlies IL-17-induced stimulation of BFU-E growth. Furthermore, Western blot analyses demonstrated no effect on early hematopoiesis transcription factor, GATA-2, and enhanced expression level of erythroid-specific factor GATA-1 in m...