Growth Of Bone Marrow Mesenchymal Stem Cells Research Articles

MicroRNA-124a promoted the differentiation of bone marrow mesenchymal stem cells into neurons through Notch signal pathway

This study investigated the possible mechanisms of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. β-Thiol ethanol induced Notch1 mRNA expression, microRNA-124a inhibitor reduced the effects of β-thiol ethanol on Notch1 mRNA expression in BMSCs. Baicalin induced Hes1 mRNA expression, and microRNA-124a inhibitor reduced the effects of baicalin on Hes1 mRNA expression in BMSCs. Si-Notch1 suppressed Hes1 mRNA expression in BMSCs. Baicalin increased the effects of Notch1 on Hes1 mRNA expression in BMSCs. Si-Notch1 increased cell growth of BMSCs. Baicalin reduced the effects of si-Notch1 on cell growth and the differentiation of BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons through Notch/Hes1 signal pathway.

Recombinant collagen coating 3D printed PEGDA hydrogel tube loading with differentiable BMSCs to repair bile duct injury

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.

In vitro evaluation of BMSCs early proliferation on minocycline-loaded electrospun nanofibers membrane.

Electrospun nanofibers could simulate the natural extracellular matrix (ECM) of the host bone, while minocycline (MINO) is a broad-spectrum tetracycline antibiotic which has been found to have multiple non-antibiotics biological effects that promotes osteogenesis in vitro and in vivo. The present study aims at constructing a polylactic acid (PLA) electrospun nanofiber membrane loaded with MINO to enhance Bone marrow mesenchymal stem cells (BMSCs) adhesion and proliferation for early clinical treatment. The MINO-PLA membrane were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR) and in vitro drug release study. The antibacterial ability was also investigated. In addition, in vitro cellular proliferation experiment was performed to verify whether the PLA electrospun nanofibers membrane loaded with MINO enhance BMSCs adhesion and proliferation. Analyzing the drug release and cell growth results, it was found that only the effective concentration of MINO-PLA could help the growth of BMSCs in the short term. This is related to the drug release rate of MINO-PLA and the initial concentration of MINO. This study shows that by controlling the concentration and release rate of MINO with electrospinning PLA, BMSCs could proliferate on it, and a new bone repair material had been made in this study.

MicroRNA-124a regulates the differentiation of bone marrow mesenchymal stem cells into neurons

Objective This study investigated the effects of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. Methods Flow cytometry was used for isolation and identification of BMSCs. Real-time polymerase chain reaction (RT-PCR) was used to detect gene mRNA expression. Apoptosis was detected using Annexin V-FITC/PI Apoptosis Detection Kit. Cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8). The differentiation of BMSCs into neuron inducers β-thiol ethanol or baicalin formed the basis of the study. Results β-thiol ethanol markedly suppressed the microRNA-124a expression of BMSCs, baicalin markedly induced the microRNA-124a expression of BMSCs and β-thiol ethanol or baicalin promoted apoptosis and reduced the growth of BMSCs. Only the microRNA-124a inhibitor did not affect apoptosis or the differentiation of BMSCs, and it increased the effects of β-thiol ethanol or baicalin on the apoptosis of BMSCs. Conclusion β-thiol ethanol and baicalin treatment could affect microRNA-124a expression in BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons.

Enhanced bone regeneration by low-intensity pulsed ultrasound and lipid microbubbles on PLGA/TCP 3D-printed scaffolds

BackgroundTo investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds.MethodsBMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation.ResultsBMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration, 2.0 MHz frequency, 0.3 W/cm2 sound intensity and 20% duty cycle. After 14 days, the type I collagen expression and alkaline phosphatase activity in the scaffold increased significantly compared to those in the control group, and alizarin red staining showed more calcium salt production during osteogenic differentiation. After 21 days, scanning electron microscopy experiments showed that osteogenesis was obvious in the PLGA/TCP scaffolds.ConclusionLIPUS combined with lipid microbubbles on PLGA/TCP scaffolds can promote BMSCs growth and bone differentiation, which is expected to provide a new and effective method for the treatment of bone regeneration in tissue engineering.

The influences of PEG-functionalized graphdiyne on cell growth and osteogenic differentiation of bone marrow mesenchymal stem cells.

Guided bone regeneration (GBR) is a frequently used technique for patients with insufficient alveolar bone. The discovery of bone substitutes that can enhance osteogenesis is critical for GBR. Graphdiyne (GDY), a newly discovered carbon-based nanomaterial, has been recognized as the most stable allotrope of acetylene carbon and is anticipated to be able to promote osteogenesis. Whereas it still remains unknown whether it could enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, GDY was modified with polyethylene glycol (PEG) and the influences of GDY-PEG at different concentrations on BMSCs cell growth and osteogenic differentiation were researched for the first time. In this study, we found that GDY-PEG at low concentration possessed premium bio-compatibility and revealed evident facilitation of BMSCs osteogenic differentiation. The cell growth and osteogenic differentiation of BMSCs treated with GDY-PEG were dose-dependent. GDY-PEG at 1μg/mL demonstrated the optimal promoting effects of BMSCs osteogenic differentiation. Moreover, the regulating effect of BMSCs osteogenic differentiation by GDY-PEG might be associated with the Wnt/β-catenin signaling pathway. In all, the present study indicated a novel application of GDY in promoting bone tissue regeneration, providing a novel biomaterial for bone augmentation in clinics.

Mechanosensitive miR-99b mediates the regulatory effect of matrix stiffness on bone marrow mesenchymal stem cell fate both in vitro and in vivo.

Mechanical signals from extracellular matrix stiffness are important cues that regulate the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the incorporation of BMSCs into soft hydrogels and the dominance of soft matrices for BMSC growth and differentiation limit the directed differentiation of BMSCs incorporated into hydrogels for tissue engineering, especially osteogenesis. Here, we found that the expression of miR-99b increased with increasing hydrogel stiffness and that miR-99b regulated the proliferation and differentiation of BMSCs seeded on the surface of substrates with different stiffnesses. Furthermore, miR-99b significantly promoted the migration of BMSCs in 3D hydrogels. Mechanistically, we demonstrated that matrix stiffness-sensitive miR-99b targets the mammalian target of the rapamycin signaling pathway to regulate the adipogenic and osteogenic differentiation of BMSCs. In addition, by modulating the expression of miR-99b, the osteogenic differentiation of BMSCs in soft 3D hydrogels was promoted. Consistently, the flexible BMSC-GelMA hydrogel transfected with miR-99b significantly promoted bone regeneration in the rat calvarial defect area. These results suggest that miR-99b plays a key role in the mechanotransduction and phenotypic transformation of BMSCs and may inspire new tissue engineering applications with MSCs as key components.

The expression of NOTUM in replantation of severed fingers may be an important treatment factor.

After years of development, digital replantation has become a mature treatment. Although the NOTUM gene has been shown to be involved in the formation of vertebrate nerves, whether it contributes to the osteogenic mechanism of severed finger replantation remains unknown. In response to this, this study investigates the specific details of NOTUM involvement in replantation of severed fingers. The experimental subjects are patientswithreplantation of severed fingers from Shulan International Medical College of Shulan (Hangzhou) Hospital affiliated to Zhejiang Shuren University. In addition to using bone marrow mesenchymal stem cells (BMSCs) as an in vitro system, this experiment also involves quantitative polymerase chain reaction, microarray analysis, cell counting Kit-8, ethynyl deoxyuridine staining and Western blot analysis. The expression level of NOTUM in the severed finger replantation group is lower than that in the normal group. NOTUM inhibits cell growth and cell transfer, osteogenic differentiation and β-catenin gene expression in BMSCs. Luciferase reporter assay illustrated that β-catenin wild type closely correlated with NOTUM. The inhibition of β-catenin increases the effects of NOTUM on cell growth, cell transfer and osteogenic differentiation of BMSCs. Considering that NOTUM can inhibit cell growth, cell transfer, osteogenic differentiation of BMSCs, as well as the gene expression of β-catenin, it may be a biomarker of osteogenic differentiation and a potential therapeutic target for replantation of severed fingers.

The Effect of Germanium-Loaded Hydroxyapatite Biomaterials on Bone Marrow Mesenchymal Stem Cells Growth.

Hydroxyapatite (HA) is a hard mineral component of mineralized tissues, mainly composed of calcium and phosphate. Due to its bioavailability, HA is potentially used for the repair and regeneration of mineralized tissues. For this purpose, the properties of HA are significantly improved by adding natural and synthetic materials. In this sense, the germanium (Ge) mineral was loaded in HA biomaterial by cold isostatic pressure for the first time and characterization and biocompatibility using bone marrow mesenchymal stem cells (BM-MSCs) were investigated. The addition of Ge at 5% improved the solubility (3.32%), stiffness (18.34 MPa), water holding (31.27%) and biodegradation (21.87%) properties of HA, compared to control. Compared to all composite biomaterials, the drug-releasing behavior of HA-3% Ge was higher at pH 1 and 3 and the maximum drug release was obtained at pH 7 and 9 with HA-5% Ge biomaterials. Among the different mediums tested, the DMEM-medium showed a higher drug release rate, especially at 60 min. HA-Ge biomaterials showed better protein adhesion and apatite layer formation, which ultimately proves the compatibility in BM-MSCs culture. Except for higher concentrations of HA (5 and 10 mg/mL), the different concentrations of Ge and HA and wells coated with 1% of HA-1% Ge had higher BM-MSCs growth than control. All these findings concluded that the fabricated HA biomaterials loaded with Ge could be the potential biomaterial for culturing mammalian cells towards mineralized tissue repair and regeneration.

Experimental study on co-culture of DiI labeled rat bone marrow mesenchymal stem cells and polycaprolactone film in vitro to make a cell patch.

In stem cell therapy, due to the lack of an effective carrier, a large number of transplanted stem cells are lost and die. Therefore, finding a suitable carrier has become a further direction of stem cell therapy. In research on the co-culture of polycaprolactone (PCL) with 1,1'-Dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate (DiI) labeled bone marrow mesenchymal stem cells (BMSCs), we observe the effect of materials on the growth and proliferation of DiI labeled stem cells, and the effect of DiI labeling on patch preparation, so as to find a kind of biomaterial suitable for the growth and proliferation of BMSCs, and find a suitable cell carrier for stem cell therapy of myocardial infarction and in vivo tracing. Clean grade Sprague Dawley rats were selected as experimental objects, BMSCs were isolated and cultured, and the surface markers were identified by flow cytometry. After the BMSCs were cultured for 3 passages, the BMSCs were stained with DiI dye, and the BMSCs DiI and PCL biomaterial film were co-cultured. After 24 hours, the cell growth was observed under fluorescence microscope, and fixed for scanning under electron microscope. The cell proliferation was detected by CCK-8 at 1, 4, 7, 10 days of culture. The measurement data conforming to normal distribution are expressed in the form of mean ± standard deviation (X¯±s). One way ANOVA was used for comparison among groups, LSD analysis was used for pairwise comparison. The difference was statistically significant (P <0.05). BMSCs were strongly positive for CD90, CD44H, but negative for CD11b/c, CD45. Under fluorescence microscope, BMSCs DiI showed red light, fusiform or polygonal. Under the scanning electron microscope, the cell patch formed by co-culture of PCL film and DiI-BMSCs had a large number of cells on the surface and normal cell state. CCK-8 assay showed that the OD value on the first day was 0.330 ± 0.025; The OD value was 0.620 ± 0.012 on the 4th day, 1.033 ± 0.144 on the 7th day and 1.223 ± 0.133 on the 10th day. There was significant difference among the time points (P <0.05). The cell patch made of PCL film and DiI labeled BMSCs can survive and proliferate on the surface, so it can be used as a scaffold material for stem cell therapy in vivo.

Krüppel-like factor 4 promotes the proliferation and osteogenic differentiation of BMSCs through SOX2/IGF2 pathway.

Human bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and have been widely researched in regenerative medicine. The purpose of this research was to explore whether Krüppel-like factor 4 (KLF4) can regulate the osteogenic differentiation of BMSCs. We transfected human BMSCs with KLF4 overexpression plasmid and si-KLF4 to study the effects of KLF4. We performed cell proliferation assay, flow cytometry and Alizarin Red staining on BMSCs. Quantitative real-time PCR and western blot was performed to determined mRNA and protein expression of osteogenic differentiation markers, KLF4, SOX2 and IGF2. Bone defect animal model was created and the adenovirus containing KLF4 overexpression or knockdown plasmid was injected. Finally, HE staining was performed on tibia to assess the new bone formation. Our results showed that KLF4 promotes not only the growth of BMSCs, but also their osteogenic differentiation. Also, it mediated these effects through SOX2/IGF2 signaling pathway. In addition, KLF4 overexpression could increase the bone regeneration in in-vivo model, whereas KLF4 knockdown decreased the bone regeneration. KLF4 regulates BMSC's osteogenic differentiation via SOX2/IGF2 pathway.

LncRNA Neu Mediates Bone Marrow Mesenchymal Stem Cells (BMSCs) Growth and Promotes Cervical Cancer Progression Through Suppression of MicroRNA-625

The tumorigenesis mechanism of cervical cancer (CC) is complicated as several pathways deserve exploration. LncRNAs are recently highlighted to be involved in various biological processes. The role of bone marrow mesenchymal stem cells (BMSCs) in tumor regulation is recently investigated. Herein, we aimed to explore the interaction between lncRNA Neu and microRNA (miR)-625 and BMSCs in CC. Expression levels of lncRNA Neu and miR-625 in CC cells and BMSCs were determined by RT-qPCR. The relationship between lncRNA Neu and miR-625 was analyzed by Pearson correlation analysis. After cancer cells were transfected with siRNA-Neu, CCK-8 assay and clone formation assay were conducted to determine cell proliferation and viability. LncRNA Neu was highly expressed in CC cells and poorly expressed in BMSCs. Knockdown of lncRNA Neu attenuated cell viability and proliferation while increased miR-625 expression. MiR-625 expression was negatively correlated with expression of lncRNA Neu in CC cells. Overexpression of miR-625 resulted in weakened CC cell viability. Collectively, lncRNA Neu was highly expressed in CC and promoted the development of CC through stimulating the growth of BMSCs and suppressing miR-625 expression. These findings provide a novel insight into targeted therapy for CC.

INTS7-ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress.

Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7–ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7–ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.

Dense Bone-Derived 3d Bioscaffold: Preparation, Characterization, and Assessment of Its Potential for Bone Marrow Mesenchymal Stem Cells (BMSCS) Growth and Differentiation

Background: Since bone defects can result in different disabilities, many efforts have been made to bone tissue engineering. In this case, scaffolds play an important role as a key element of tissue engineering in providing three-dimensional structure for cell growth in vitro Objective: The aim of the present study was to provide the three-dimensional biological bioscaffold from the bovine femur dense bone and investigate the possibility of its potential for application in tissue engineering as biological 3D ECM bioscaffold via mesenchymal stem cells seeding and differentiation toward bone tissue. Methods: For the preparation of bioscaffolds, after cutting bovine femur bone into small pieces, demineralization and decellularization were done. Bioscaffolds biocompatibility was evaluated using an MTT assay. The morphological and cell adhesion characteristics of Bone marrow mesenchymal stem cells (BMSCs) on the bioscaffolds were evaluated using Scanning Electron Microscopy (SEM) technique. Finally, the cells were treated with an osteogenic differentiation medium and then evaluated for differentiation. Results: Histological studies showed that the use of sodium dodecyl sulfate (2.5%) for 8 h eliminated the cells. Radiography and calcium oxalate test confirmed demineralization. MTT assay and SEM studies showed that the obtained bioscaffolds are biocompatible and could provide an optimum three-dimensional environment for cell adhesion and movement. Moreover, the Alizarin red staining showed a higher differentiation rate for BMSCs. Conclusion: In the present study, bone-derived 3D bioscaffold showed an important role in the growth and differentiation of BMSCs, due to the natural characteristics, cell adhesion properties, and potential to enhance differentiation toward bone tissue. It may have the potential for use as bioscaffold as supporting metrics for maintenance, growth in bone tissue engineering.

Gradient Mineralized and Porous Double-Network Hydrogel Effectively Induce the Differentiation of BMSCs into Osteochondral Tissue In Vitro for Potential Application in Cartilage Repair.

At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.

Nanoparticle encapsulated core-shell hydrogel for on-site BMSCs delivery protects from iron overload and enhances functional recovery

The local microenvironment may influence the success of stem cell therapy. Iron overload occurs in many hemorrhagic injuries due to hemolysis and hemoglobin degradation, which not only mediates local cell injury, but also induces damage to the transplanted cells. Here, an injectable nanoparticle encapsulated core-shell hydrogel was fabricated for simultaneous iron overload clearance and bone marrow mesenchymal stem cells (BMSCs) transplantation following intracerebral hemorrhage (ICH). The iron chelator-loaded low-molecular-weight keratin hydrogel with quick degradation property was selected as the outer shell to eliminate iron overload, and BMSCs implantation with high-molecular-weight keratin hydrogel was selected as the inner core. The epidermal growth factor and the basic fibroblast growth factor were entrapped within the poly (lactic-co-glycolic acid) (PLGA) nanoparticle, which was then encapsulated into the core hydrogel to support the BMSC growth and differentiation. The core-shell hydrogel can be easily formed by programmed injections, and the core-shell hydrogel displayed a strong protective effect against the toxicity of hemoglobin in cell experiments. Furthermore, more BMSCs survived in the core-shell hydrogel group in vivo as compared to that in the core hydrogel group and the vehicle group. Less iron deposition and ventricular enlargement, lower brain water content, and faster neurological recovery were also observed. The data demonstrated that this core-shell hydrogel is an effective strategy for promoting transplanted cell survival under the condition of an iron overload.

Yam-Containing Serum Promotes Proliferation and Chondrogenic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells and Synthesis of Glycosaminoglycan

The chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is affected by a variety of factors, including environmental, physical, and chemical factors and growth factors, and traditional Chinese medicine (TCM) preparations can further influence this process. In this study, the effects of different concentrations of Yam-containing serum of rabbits on BMSC proliferation and chondrogenic differentiation were investigated, as were the underlying molecular mechanisms. The growth and proliferation of BMSCs were significantly enhanced upon treatment with Yam-containing serum. Under both monolayer and micromass culture conditions, Yam-containing serum promoted the differentiation of BMSCs into chondrocytes. Toluidine blue staining results revealed that chondrocyte differentiation in the group treated by Yam-containing serum was significantly more pronounced than in the control group. Glycosaminoglycan levels, as measured by 1,2-dimethylmethylene blue (DMMB) detection, were significantly higher in cells of the Yam-containing group relative to the control group. This is the first study to our knowledge that demonstrates that Yam-containing serum can promote BMSC proliferation and chondrogenic differentiation. This study therefore lays an experimental groundwork for further application of TCM as a means of treating degenerative cartilage diseases and provides an experimental and theoretical basis for the combination of TCM and stem cells for the treatment of such diseases.

Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation

Background: Researches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach. Methods: Transwell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot. Results: Androgen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling. Conclusions: This study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro . Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.

Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation.

BackgroundResearches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach.MethodsTranswell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot.ResultsAndrogen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling.ConclusionsThis study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro. Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.

Mesenchymal stem cell-loaded porous tantalum integrated with biomimetic 3D collagen-based scaffold to repair large osteochondral defects in goats

BackgroundThe body is unable to repair and regenerate large area bone defects. Moreover, the repair capacity of articular cartilage is very limited. There has long been a lack of effective treatments for osteochondral lesions. The engineered tissue with biphase synthetic for osteochondral repair has become one of the hot research fields over the past few years. In this study, an integrated biomanufacturing platform was constructed with bone marrow mesenchymal stem cells (BMSCs)/porous tantalum (pTa) associated with chondrocytes/collagen membranes (CM) to repair large osteochondral defects in load-bearing areas of goats.MethodsTwenty-four goats with a large osteochondral defect in the femoral heads of the left hind legs were randomly divided into three groups: eight were treated with chondrocytes/CM-BMSCs/pTa, eight were treated with pure CM-pTa composite, and the other eight goats were untreated. The repair effect was assessed by X-ray, gross observation, and histomorphology for 16 weeks after the operation. In addition, the biocompatibility of chondrocytes/CM-BMSCs/pTa was observed by flow cytometry, CCK8, immunocytochemistry, and Q-PCR. The characteristics of the chondrocytes/CM-BMSCs/pTa were evaluated using both scanning electron microscopy and mechanical testing machine.ResultsThe integrated repair material consists of pTa, injectable fibrin sealant, and CM promoted adhesion and growth of BMSCs and chondrocytes. pTa played an important role in promoting the differentiation of BMSCs into osteoblasts. Three-dimensional CM maintained the phenotype of chondrocytes successfully and expressed chondrogenic genes highly. The in vivo study showed that after 16 weeks from implantation, osteochondral defects in almost half of the femoral heads had been successfully repaired by BMSC-loaded pTa associated with biomimetic 3D collagen-based scaffold.ConclusionsThe chondrocytes/CM-BMSCs/pTa demonstrated significant therapeutic efficacy in goat models of large osteochondral defect. This provides a novel therapeutic strategy for large osteochondral lesions in load-bearing areas caused by severe injury, necrosis, infection, degeneration, and tumor resection with a high profile of safety, effectiveness, and simplicity.