scholarly journals Neurobiological Observations of Bone Mesenchymal Stem Cells in vitro and in vivo of Injured Sciatic Nerve in Rabbit

2011 ◽  
Vol 10 (6) ◽  
pp. 686-691 ◽  
Author(s):  
Al-Timmemi Hameed ◽  
R. Ibrahim ◽  
Al-Jashamy Karim ◽  
Abz Zuki ◽  
Ti. Azmi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sciatic Nerve ◽  
Bone Mesenchymal Stem Cells

scholarly journals Tenuigenin promotes the osteogenic differentiation of bone mesenchymal stem cells in vitro and in vivo

2016 ◽  
Vol 367 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Hua-ji Jiang ◽  
Xing-gui Tian ◽  
Shou-bin Huang ◽  
Guo-rong Chen ◽  
Min-jun Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Mesenchymal Stem Cells

Bone mesenchymal stem cells derived extracellular vesicles promotes TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p

2020 ◽  
pp. 1-13
Author(s):  
Lu Deng ◽  
Chang Wang ◽  
Chao He ◽  
Li Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Cell Apoptosis ◽  
Bone Mesenchymal Stem Cells ◽  
Hcc Cells

OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. METHODS: BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. RESULTS: EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. CONCLUSION: BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

scholarly journals Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Huangdi Li ◽  
Jinghui Huang ◽  
Yanpeng Wang ◽  
Ziyuan Chen ◽  
Xing Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surface Characteristics ◽  
Titanium Implants ◽  
Bone Mesenchymal Stem Cells ◽  
H2o2 Treatment ◽  
Cell Behaviors ◽  
Rat Bone

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters’ influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

scholarly journals Adipose-Derived Mesenchymal Stem Cells From a Hypoxic Culture Improve Neuronal Differentiation and Nerve Repair

2021 ◽  
Vol 9 ◽  
Author(s):  
Szu-Hsien Wu ◽  
Yu-Ting Liao ◽  
Kuang-Kai Hsueh ◽  
Hui-Kuang Huang ◽  
Tung-Ming Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Sciatic Nerve ◽  
Neuronal Differentiation ◽  
Gastrocnemius Muscle ◽  
Differentiation Potential ◽  
Neuronal Markers

Hypoxic expansion has been demonstrated to enhance in vitro neuronal differentiation of bone-marrow derived mesenchymal stem cells (BMSCs). Whether adipose-derived mesenchymal stem cells (ADSCs) increase their neuronal differentiation potential following hypoxic expansion has been examined in the study. Real-time quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were employed to detect the expression of neuronal markers and compare the differentiation efficiency of hypoxic and normoxic ADSCs. A sciatic nerve injury animal model was used to analyze the gastrocnemius muscle weights as the outcomes of hypoxic and normoxic ADSC treatments, and sections of the regenerated nerve fibers taken from the conduits were analyzed by histological staining and immunohistochemical staining. Comparisons of the treatment effects of ADSCs and BMSCs following hypoxic expansion were also conducted in vitro and in vivo. Hypoxic expansion prior to the differentiation procedure promoted the expression of the neuronal markers in ADSC differentiated neuron-like cells. Moreover, the conduit connecting the sciatic nerve gap injected with hypoxic ADSCs showed the highest recovery rate of the gastrocnemius muscle weights in the animal model, suggesting a conceivable treatment for hypoxic ADSCs. The percentages of the regenerated myelinated fibers from the hypoxic ADSCs detected by toluidine blue staining and myelin basic protein (MBP) immunostaining were higher than those of the normoxic ones. On the other hand, hypoxic expansion increased the neuronal differentiation potential of ADSCs compared with that of the hypoxic BMSCs in vitro. The outcomes of animals treated with hypoxic ADSCs and hypoxic BMSCs showed similar results, confirming that hypoxic expansion enhances the neuronal differentiation potential of ADSCs in vitro and improves in vivo therapeutic potential.

scholarly journals Bone mesenchymal stem cells stimulation by magnetic nanoparticles and a static magnetic field: release of exosomal miR-1260a improves osteogenesis and angiogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Di Wu ◽  
Xiao Chang ◽  
Jingjing Tian ◽  
Lin Kang ◽  
Yuanhao Wu ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Magnetic Nanoparticles ◽  
Bone Regeneration ◽  
Static Magnetic Field ◽  
Expression Profiles ◽  
Bone Mesenchymal Stem Cells

Abstract Background The therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved. Methods Two novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro. Results 50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively. Conclusion These results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future. Graphical abstract

scholarly journals Exosomes from Human Gingiva-Derived Mesenchymal Stem Cells Combined with Biodegradable Chitin Conduits Promote Rat Sciatic Nerve Regeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Feng Rao ◽  
Dianying Zhang ◽  
Tengjiaozi Fang ◽  
Changfeng Lu ◽  
Bo Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peripheral Nerve Regeneration

At present, repair methods for peripheral nerve injury often fail to get satisfactory result. Although various strategies have been adopted to investigate the microenvironment after peripheral nerve injury, the underlying molecular mechanisms of neurite outgrowth remain unclear. In this study, we evaluate the effects of exosomes from gingival mesenchymal stem cells (GMSCs) combined with biodegradable chitin conduits on peripheral nerve regeneration. GMSCs were isolated from human gingival tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot, and size distribution analysis. The effects of exosomes on peripheral nerve regeneration in vitro were evaluated by coculture with Schwann cells and DRGs. The chitin conduit was prepared and combined with the exosomes to repair rat sciatic nerve defect. Histology, electrophysiology, and gait analysis were used to test the effects of exosomes on sciatic nerve function recovery in vivo. We have successfully cultured GMSCs and isolated exosomes. The exosomes from GMSCs could significantly promote Schwann cell proliferation and DRG axon growth. The in vivo studies showed that chitin conduit combined with exosomes from GMSCs could significantly increase the number and diameter of nerve fibers and promote myelin formation. In addition, muscle function, nerve conduction function, and motor function were also obviously recovered. In summary, this study suggests that GMSC-derived exosomes combined with biodegradable chitin conduits are a useful and novel therapeutic intervention in peripheral nerve repair.

Lentiviral-mediated ho-1 gene transduced bone mesenchymal stem cells protects against acute graft-Versus-host disease in vitro and vivo

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4675-4675
Author(s):  
Jishi Wang ◽  
Dan Ma ◽  
Yan Li ◽  
Qin Fang ◽  
Shuya Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Natural Science ◽  
Research Funding ◽  
Rt Pcr ◽  
Bone Mesenchymal Stem Cells ◽  
Group D

Abstract Abstract 4675 Objective: Bone mesenchymal stem cells (BMSCs) possessing immunoregulatory activities have been evaluated in the treatment of graft-versus-host disease (GVHD). In this study, mice's heme oxygenase 1 (HO-1) was transduced into mice's bone marrow-derived mesenchymal stem cells (mBMSCs), we assessed the immuno-suppressive capacity of lentiviral vector transduced BMSCs expressing HO-1 in BALB/c mice aGVHD model, and the immuno-regulatory effect of mBMSCs on alleviating acute GVHD in vivo was measured to provide laboratory data for gene therapy for aGVHD which used mBMSCs as vehicles. Methods: We cloned mice's HO-1 cDNA from mice's bone marrow and constructed recombinant lentivirus vectors (Lentivirus-V5-D-TOPO-HO-1-EGFP/Lentivirus–V 5-D-TOPO-EGFP) which titer was 1×1011 pfu/mL. These mBMSCs were separated, cultured, purified, and detected by morphology, flow cytometry, osteogenic, adipogenic and chondrogenic induction, and the mRNA level of the neural ganglioside GD2 gene which is a surface marker for the identification of MSCs by RT-PCR. Then recombinant vectors were transferred into mBMSCs, and the expression of EGFP and HO-1 were detected by fluorescence microscope, RT-PCR and Western blot respectively. The immunsuppressive capacity of HO-1 over-expressing mBMSCs was investigated using transwell assay in vitro. And before infusion, the homing of MSC was detected by Flow cytometry. In addition, we established BALB/c mice's aGVHD model after Allo-HSCT, the recombinant vectors tranfected mBMSCs and primary mBMSCs were injected into the BALB/c mice aGVHD model in tail vein, respectively. Four groups were separated in vivo test (Group A: aGVHD control; Group B: aGVHD model injected in mBMSCs; Group C: aGVHD model injected in mBMSCs transfected with EGFP; Group D: aGVHD model injected in mBMSCs transfected with HO-1 gene.) The survival, body weight and clinical score of GVHD in transplanted mice were monitored to evaluate the severity of aGVHD. The aGVHD targeted organ, such as Liver, intestine and lung from mice in each group were obtained for histological examination and pathological score. Plasma concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ and TNF-γ were also determined using a Cytometric Bead Array. Results: We cloned mice HO-1 gene from mice's bone marrow and constructed the recombinant adenovirus vectors (Lentivirus-V5-D-TOPO-HO-1- EGFP/Lentivirus-V5-D-TOPO-EGFP) successfully. mBMSCs was separated and identified successfully. Fluorescence microscope detected the expression of EGFP, while both RT-PCR and Western blot detected high expression of HO-1 in gene-transfected group cells. It clearly showed that mBMSCs in Group D can migrate more through the polycarbonate filter toward bone marrow micro-environment in the lower chamber than Group A, B, C in vitro, while homing of Group D showed similar trend compared with others groups. In the mice GVHD model, treatment with HO-1 over-expressing BMSCs significantly decreased the mortality rate and attenuated clinical and pathological GVHD scores, and volume of spleen was not more obviously enlarged than others groups. Moreover, compared with control groups, the plasma IL-2, IL-6, IFN-γ and TNF-γ levels in recipients infused with HO-1 over-expressing BMSCs were significantly decreased, while those of IL-4 and IL-10 were increased. Conclusion: Lentiviral vectors carrying the HO-1 were successfully used to transduce mBMSCs. In our report, mBMSCs transferred with lentiviral vectors expressed strongerly immunoregulatory activities to alleviate aGVHD. Not only did HO-1 enhance that migration of mBMSCs, but also strengthen homing of MSCs. In vivo experiments, the evidence of survival rate, body weight, clinical score and pathological score fully proved that HO-1-transduced BMSCs effectively controlled the occurrence of mice's aGVHD following allogeneic BM transplantation, and HO-1 may be a potential target to overcome aGVHD in vivo. Disclosures: Ma: National Natural Science Foundation of China: Research Funding. Li:National Natural Science Foundation of China: Research Funding. Fang:National Natural Science Foundation of China: Research Funding. Chen:National Natural Science Foundation of China: Research Funding. Sun:National Natural Science Foundation of China: Research Funding.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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