scholarly journals Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Dexiao Kong ◽  
Xia Liu ◽  
Xiaomei Li ◽  
Jianting Hu ◽  
Xiaoyan Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Rabbit Model ◽  
Lower Lobe ◽  
The Body ◽  
Inflammatory Factors ◽  
Individual Treatment ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Chest Imaging ◽  
Tnf Α

Abstract The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

scholarly journals Overexpression of HNF4α enhances umbilical cord mesenchymal stem cell function to treat acute liver failure in mice through macrophage polarization

2020 ◽  
Author(s):  
Yeping Yu ◽  
Qiqi Zhang ◽  
Ning Wu ◽  
Lei Xia ◽  
Jie Cao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Umbilical Cord ◽  
Macrophage Polarization ◽  
The Body ◽  
Inflammatory Factors ◽  
Human Umbilical Cord ◽  
Therapeutic Effects

Abstract Background: Advances in research on stem cell therapy provide new feasible solutions for acute liver failure (ALF) treatment. Recent studies have demonstrated that the expression of hepatocyte nuclear factor 4α (HNF4α) reset within the damaged hepatocytes can restore normal physiological function. This study aimed to determine the role of human umbilical cord mesenchymal stem cells (HuMSCs) overexpressing HNF4α in ALF treatment.Method: We isolated and cultured HuMSCs in vitro, reversed it by lent virus expression HNF4α (hereinafter referred to as HuMSC-HNF4α). HuMSC-HNF4α was intraperitoneally administrated into the mice immediately after exposed to D-galactosamine / lipopolysaccharide (D-galn / LPS). To investigate their effects in ALF, we performed liver histological and serumbiochemical analysis. Macrophages differentiation and cytokines secreted by HuMSCs were evaluated to elucidate its mechanisms.Results: We found HuMSC-HNF4α has more obvious therapeutic effects on ALF than the negative control virus transfected the HuMSCs (HuMSC-CON). In vitro, HuMSC-HNF4α promotes the polarization of liver macrophages (Kupffer cells) to M2 phenotype, inhibits the inflammatory response of macrophages and reduces the levels of inflammatory factors such as TNF-α, IL-1β to reduce liver damage.Conclusion: Our research confirmed that the therapeutic effect of HuMSC-HNF4α on ALF is not the same as the previous passive support but an active intervention on excessive inflammation in the body. This provides new ideas for research and clinical practice in the future.

scholarly journals The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

2020 ◽  
Author(s):  
Fatchiyah Fatchiyah ◽  
Rista Nikmatu Rohmah ◽  
Lidwina Faraline Triprisila ◽  
Takeshi Ohta ◽  
Hazna Noor Meidinna
Keyword(s):  
Body Weight ◽  
Diabetes Management ◽  
Diabetic Rats ◽  
The Body ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Caprine Milk ◽  
Type2 Diabetes ◽  
Tnf Α ◽  
Protein Treatment

This study purpose was to investigate the association of casein-alpha-S2 protein of Caprine milk and molecular mechanismofinsulin signaltransduction in type2 diabetes mellitus (T2DM). The Caprine milk CSN1S2 protein treatment of 0, 375, 750, and 1500mg/kg BW were conducted to the control and T2DM rats. We observed several physiological parameters of all rats. The levels of insulin and TNF-α in the plasma were measured using ELISA.The expressions of proteins and mRNA levels of diabetes-related genes in the pancreas tissues were analyzed using Western Blotting and Real-Time PCR, respectively. Our study found that diabetic rats had lower body weight, food intake, and fecal weight compared with control rats. The Caprine milk CSN1S2 protein consumption affected the body weight of diabetic rats to increase, especially at the dose of 750mg/kg BW.Interestingly, the genes associated with insulin signaling were improved by the CSN1S2 protein treatment in diabetic rats, although their blood glucose and cholesterol level were not affected. The diabetic rats showed an elevated insulin level and GLUT4 protein expression after treatment. We also reported that the CSN1S2-treated diabetic rats had a gradually reduced expression of TNF-α and VCAM-1 in dose-dependent. Moreover, the 750mg/kg BW of CSN1S2 treatment enhanced the mRNA expressions of INS-receptor, GLUT4, IGF-1, CAMKK, and CAMKIV in diabetic rats. The ability of Caprine milk CSN1S2 protein to regulate the molecular mechanisms in the diabetes-signaling pathway indicated its potential therapeutic effects on diabetes management.

scholarly journals Overexpression of HNF4α enhances umbilical cord mesenchymal stem cell function to treat acute liver failure in mice through macrophage polarization

2020 ◽  
Author(s):  
Yeping Yu ◽  
Qiqi Zhang ◽  
Ning Wu ◽  
Lei Xia ◽  
Jie Cao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Umbilical Cord ◽  
Macrophage Polarization ◽  
The Body ◽  
Inflammatory Factors ◽  
Human Umbilical Cord ◽  
Therapeutic Effects

Abstract Background and aim: Advances in research on stem cell therapy provide new feasible solutions for acute liver failure (ALF) treatment. Recent studies have demonstrated that the expression of hepatocyte nuclear factor 4α (HNF4α) reset within the damaged hepatocytes can restore normal physiological function. This study aimed to determine the role of human umbilical cord mesenchymal stem cells (HuMSCs) overexpressing HNF4α in ALF treatment. Method: HuMSCs in vitro were isolated, cultured, and reprogrammed by the lentiviral expression of HNF4α (hereinafter referred to as HuMSC-HNF4α). HuMSC-HNF4α was intraperitoneally administered into the mice immediately after exposed to D-galactosamine/lipopolysaccharide (D-galN/LPS). The liver histological and serum biochemical analyses were performed to investigate the effects of HuMSC-HNF4α in ALF. Macrophages differentiation and cytokines secretion by HuMSCs were evaluated to elucidate the underlying mechanisms. Results: HuMSC-HNF4α had more obvious therapeutic effects on ALF compared with negative control virus-transfected the HuMSCs (HuMSC-CON). In vitro, HuMSC-HNF4α promoted the polarization of liver macrophages (Kupffer cells) to the M2 phenotype, inhibited the inflammatory response of macrophages, and reduced the levels of inflammatory factors such as TNF-α and IL-1β to reduce liver damage. Conclusions: This study confirmed that the therapeutic effect of HuMSC-HNF4α on ALF was not the same as the previous passive support but as active intervention on excessive inflammation in the body. The findings provided new ideas for research and clinical practice in the future.

scholarly journals Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate experimental autoimmune encephalomyelitis via regulating pro and anti-inflammatory cytokines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Ahmadvand Koohsari ◽  
Abdorrahim Absalan ◽  
Davood Azadi
Keyword(s):  
Spinal Cord ◽  
Body Weight ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Clinical Score ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Leukocyte Infiltration ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractThe therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

Pterostilbene Ameliorates Nephropathy Injury in Streptozotocin-Induced Diabetic Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Ying Zhang ◽  
Shaoyu Ren ◽  
Ying Ji ◽  
Yafeng Liang
Keyword(s):  
High Fat Diet ◽  
Nuclear Factor Κb ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Different Doses

Background: Our study investigated the therapeutic role and potential mechanisms of pterostilbene (PS) in diabetic nephropathy (DN) rats. Methods: DN models were established by high-fat diet after streptozotocin injection. A total of 50 Sprague-Dawley rats were randomly divided into control, DN, PS-treated groups (PS-H, PS-M, PS-L). PS was administered to rats by gavage for 8 weeks at 3 different doses (25, 10, and 5 mg/kg/day). The levels of oxidative stress activity (superoxide dismutase [SOD], malondialdehyde [MDA], glutathione peroxidase [GSH-PX]) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin (IL)-6, IL-1β, monocyte chemoattractant factor [MCP]-1) were detected by ­ELISA. TGF-β, Smad1, and fibronectin (FN) were measured through immunohistochemistry. The relative expressions of phospho-IκBα/IκBα, phospho-IκB kinases (IKK)β/IKKβ, phospho-nuclear factor-κB (NF-κB) p65/NF-κB p65 were detected by western blot. Results: Compared with DN group, the levels of TNF-α, IL-6, IL-1β, and MCP-1 were decreased in the PS-H group (p < 0.05). Meanwhile, the levels of SOD, MDA, GSH-PX improved in kidney and serum in PS-H groups (p< 0.05). PS also significantly decreased the level of phospho-NF-κB p65 and increased the levels of phospho- IKKβ and phospho-Iκ-Bα (p < 0.05). The results showed that PS treatment decreased TGF-β, Smad1, and FN expressions. Conclusion: PS had potential therapeutic effects on DN, which may be related to the regulation of NF-κB pathway.

Regenerative effects of mesenchymal stem cells by dosage in a chronic rotator cuff tendon tear in a rabbit model

2019 ◽  
Vol 14 (11) ◽  
pp. 1001-1012
Author(s):  
Dong Rak Kwon ◽  
Gi-Young Park ◽  
Sang Chul Lee
Keyword(s):  
Rotator Cuff ◽  
Motion Analysis ◽  
Rabbit Model ◽  
Optimal Dose ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Full Thickness ◽  
Tendon Tear ◽  
Rotator Cuff Tendon

Aim: We investigated the therapeutic effects and optimal dose of human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection in a chronic full-thickness rotator cuff tendon tear. Methods: Rabbits (n = 30) were allocated into three groups (normal saline, G1-Sal; 1 × 106 cells UCB-MSC, G2-Low; 2 × 106 cells UCB-MSC, G3-High). Injections were done into the chronic full-thickness rotator cuff tendon tear 6 weeks after a full-thickness tendon tear of the subscapularis was created. Gross & histologic evaluation and motion analysis was done at pre and 4 weeks post-injection. Results: There were no significant differences in tear size and motion analysis parameters 4 weeks after injection between G2-Low and G3-High. Conclusion: The benefits of UCB-MSCs are not dose-dependent in a rabbit model.

scholarly journals Exosomes derived from mesenchymal stem cells inhibit catabolism in human chondrocytes by activating autophagy via inhibition of the NF-κB pathway

2020 ◽  
Author(s):  
Jian-Fa Wang ◽  
Zhi Zhu ◽  
Lei Sun ◽  
Shi-kun Shao ◽  
Bao-dong Ma ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Primary Cultures ◽  
Human Chondrocytes ◽  
Inflammatory Factors ◽  
Human Umbilical Cord ◽  
Adult Males ◽  
New Therapeutic Approaches ◽  
Inflammatory Conditions ◽  
Tnf Α

Abstract Objective: We aimed to determine the significance of MSC-derived exosomes (MSC-Exos) in chondrocyte autophagy under normal and inflammatory conditions.Design: Human umbilical cord-derived MSCs (hMSCs) were cultured in vitro. hMSC-Exos( EX） were isolated by an ultracentrifugation method. Transmission electron microscopy and western analysis were used to identify exosomes. Human chondrocytes were extracted from five adult males with OA undergoing total knee arthroplasty. Primary cultures of chondrocytes from OA patients were stimulated with 50 ng/ml tumor necrosis factor-α (TNF-α) in the presence or absence of hMSC-Exos. Autophagy levels were determined based on expression of autophagic marker LC3, StubRFP-SensGFP-LC3 analysis, and electron microscopy. Catabolic gene and chemokine expression were evaluated using quantitative PCR. The NF-κB inhibitor NS398 was used to analyze the role of the NF-κB pathway in autophagic activation.Results: hMSC-Exos increased LC3-II levels as well as autophagosome number in chondrocytes. hMSC-Exos inhibited TNF-α–induced expression of MMP-3, -9, and -13; ADAMTS5; CCL-2 and -5; and CXCL1. NF-κB inhibition activated autophagy in TNF-α–treated chondrocytes. These results indicate that hMSC-Exos might suppress the levels of catabolic and inflammatory factors in chondrocytes by promoting autophagy via NF-κB pathway inhibition.Conclusions: Our data support the interest in hMSC-Exos to develop new therapeutic approaches for joint conditions.

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