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Objective To study the effect of autologous bone marrow mesenchymal stem cells in the treatment of osteonecrosis .Methods 56 cases of osteonecrosis of femeral head ( ONFH) were treated with autologous bone marrow mesenchymal stem cells .DSA observed neovascularization after transplantation ,morphological changes of femoral head were observed by imaging method .Results Of the 30 patients who underwent autologous bone marrow stem cell transplantation,86.6％had resuscitation of hip pain,23.3％ had improved hip function,and 85.7％ had walking distance .Examination showed that the arterial artery was significantly increased before transplantation , thickening,faster blood flow.The femoral head area of the bone was significantly improved (100.0％) after 12 -24 months.Conclusion The method of transplantation of bone marrow mesenchymal stem cells is simple ,safe and effective.It is effective for stage I and II of the avascular necrosis of the femoral head .
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Objective To evaluate the effect of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on cognitive function in endotoxemic rats.Methods Seventy-two pathogen-free male Wistar rats,aged 180-250 g,were randomly divided into 4 groups (n=18 each) using a random number table:control group (group C),endotoxemia group (group E),UC-MSC group (group M),and endotoxemia+ MSC group (group PM).Cognitive function was assessed using Morris water maze test.At 4 h before training on 2nd day of place navigation test,lipopolysaccharide 100 μg/kg was injected intraperitoneally in group E,the equal volume of normal saline was given in group C,UC-MSC suspension 300 μl (5× 105cells,the fluid was normal saline) was injected via the tail vein immediately after intraperitoneal lipopolysaccharide in group PM,and UC-MSCs were injected via the tail vein in group M.At 4 h after injection,Morris water maze test was continued.At 4,24 h and 5 days after intraperitoneal injection or injection via the tail vein (T1-3),6 rats were selected,and blood samples were collected from hearts.The rats were then sacrificed,and the hippocampus was removed.The levels of interleukin-lbeta (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) in serum and hippocampus were determined.Results Compared with group C,the escape latency was significantly prolonged on 2nd and 3rd days of Morris water maze test,the number of crossing the platform was significantly decreased,the percentage of swimming distance in 1 st quadrant in the total swimming distance was significantly decreased,and the levels of IL-1 β,IL-6 and TNF-α in serum and hippocampus were significantly increased at T1,2 in group E (P＜0.05).Compared with group E,the escape latency was significantly shortened on 2nd and 3rd days of Morris water maze test,the number of crossing the platform was significantly increased,the percentage of swimming distance in 1st quadrant in the total swimming distance was significantly increased,and the levels of IL-1β,IL-6 and TNF-α in serum and hippocampus were significantly decreased at T1,2 in group PM (P＜0.05).Conclusion UC-MSC transplantation can improve the cognitive decline in endotoxemic rats.
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Multiple sclerosis (MS) is the most common neurological disease in young adults, affecting approximately two million people worldwide nowadays. Unfortunately, there was no effective treatment and interventional method for MS at present. Even the current standard treatment consisting of disease-modifying drugs can only alleviate the clinical symptoms of MS, and these drugs may produce serious adverse side effects, and are ineffective in preventing disease progression in many MS patients. Mesenchymal stem cell therapy (MSCT) in animal models and primary clinical trials have shown potential effect consisting of neuroregeneration and immunomodulation. Therefore, the treatment with mesenchymal stem cells (MSCs) may present a promising tool for the treatment of MS patients.
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Objective To investigate the effect of hypoxic preconditioning on anti-inflammatory responses of bone marrow mesenchymal stem cells (BMSCs) in rats through in vitro and in vivo experiments.Methods In vitro experiment The isolated rat BMSCs were cultured by whole bone marrow adherence method.The cells at passage 3 were seeded in 24-well plates at a density of 1 × 106 cells/ml and randomly divided into 5 groups (n =8 wells each) using a random number table:control group (group C),normoxia-incubated group (group N),hypoxic preconditioning group (group H),hypoxia preconditioning + STAT3 inhibitor Stattic group (group HS) and hypoxia preconditioning + anti-IL-10 monoclonal antibody group (group HA).In group C,BMSCs were incubated in DMEM culture medium.In group N,BMSCs were exposed to21％ O2-74％ N2-5.0％ CO2 for48 h.In group H,BMSCs were exposed to 0.5％ O2-94.5％ N2-5.0％ CO2 for 24 h followed by 24 h exposure to normoxia.In HS and HA groups,500 μg/ml Stattic and 100 μg/rnl anti-IL-10 monoclonal antibody were added to the culture medium before hypoxia preconditioning,respectively.The expression of phosphorylated STAT3 (p-STAT3) and IL-10 was determined by Western blot.In vivo experiment Healthy male Sprague-Dawley rats,weighing 300-350 g,in which intrathecal catheters were successfully implanted without complications,underwent spinal cord ischemia by occlusion of the thoracic aorta combined with controlled hypotension.Three hundred rats with spinal cord I/R injury were randomly divided into C,N,H,HS and HA groups (n =60 each) using a random number table.Immediately after onset of reperfusion,DMEM medium 300 μl was injected intrathecally in group C,and BMSC suspension 300 μl (1 × 106 cells/ml) was injected intrathecally in N,H,HS and HA groups.Neurological function was scored before ischemia and at 4,12,24 and 48 h of reperfusion (T0-,).The animals were then sacrificed and the lumbar segment of spinal cord was removed for detection of the content of IL-10,TNF-α,IL-1β,IL-6,monocyte chemotactic protein-1 (MCP-1),and macrophage inflammatory protein-1 α (MIP-1 α) (by ELISA) and the number of activated microglia (by immuno-histochemistry).Results Compared with C and N groups,the expression of pSTATβ and IL-10 was significantly up-regulated,the neurological function score and IL-10 content were increased,the content of TNF-α,IL-1β,IL-6,MCP-1 and MIP-1α and the number of activated microglia were decreased in group H (P ＜ 0.05).Compared with group H,the expression of p-STAT3 and IL-10 in group HS and expression of IL-10 in group HA was significantly down-regulated,and the neurological function score and IL-10 content were decreased,and the content of TNF-α,IL-13,IL-6,MCP-1 and MIP-1α and the number of activated microglia were increased in HS and HA groups (P ＜ 0.05).Conclusion Hypoxic preconditioning can enhance anti-inflammatory effects of BMSCs,thus increasing BMSCs-induced reduction of spinal cord ischemia-reperfusion injury in rats.
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Objective To investigate the mechanism of acute inflammatory response and tissue repair when rats accepted transplanted bone marrow mesenchymal stem cells (MSC) in severe acute pancreatitis (SAP).Methods A total of 40 rats were randomly divided into 4 groups which included the normal group (n=10),the model severe acute pancreatitis group (n=10),the transplanted bone marrow mesenchymal stem cells group (n =10),and the combination of bone marrow mesenchymal stem cells and granulocyte colony-stimulating factor (G-CSF) group (n=10).To cure the acute severe pancreatic injury caused by SAP,rats were injected with EDU-labeled MSCs and granulocyte colonystimulating factor (Gr-CSF).The conversion rate of MSCs to pancreatic cells or MSCs to endothelial cells was detected to assess the role of MSCs in tissue regeneration and repair.The expression of amylase,interleukin-6 (IL-6),and interleukin-10 (IL-10) in serum was detected to assess the role of MSCs in an acute inflammatory response.Results The concentrations of amylase and IL-6 were reduced and the concentration of IL-10 was increased in MSC and MSC+G-CSF groups after the onset of SAP.Flow cytometry showed a small amount of MSCs converting to endothelial or pancreatic cells,but the conversion rate was relatively low.Conclusions MSCs can play an important role in the antipre-release of inflammatory mediators,reducing acute immune response to control the acute inflammatory response in SAP.Moreover,MSCs can repair a damaged pancreas by converting into both pancreatic and endothelial cells.
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Objective To investigate the effect of erythropoietin (EPO) on mesenchymal stem cells (mMSCs) proliferation under acute kidney injury (AKI) microenvironment,and to study its possible mechanism.Methods C57BL/6 mice's MSCs (mMSCs) were isolated by Percoll density gradient centrifugation and adherence cultivation.Surface markers were identified by flow cytometry.AKI mice models were made by clamping bilateral renal pedicles for 30 minutes and reopening for 30 minutes.Then both renal cortex was drew immediately to make IR kidney homogenate supernatant.P3-mMSCs were divided into different groups: Group A: low glucose DMEM medium with 10% fetal bovine serum; Group B: low glucose DMEM medium with 10% fetal bovine serum plus IR kidney homogenate supernatant; Group C: low glucose DMEM medium with 10% fetal bovine serum plus IR kidney homogenate supernatant and different concentrations of EPO (1,5,10,50 U/ml).Each group was incubated for 1 d,3 d,5 d,7 d.Proliferation of mMSCs was detected by CCK-8,and apoptosis was detected by TUNEL.The protein expression of erythropoietin receptor(EPOR) and the proteins of proliferation/apoptosis related signal pathway were examined by Western blotting.Results Under IR kidney homogenate supernatant,the proliferation ability of mMSCs decreased significantly (P＜0.01),while the apoptoic percentage was significantly higher than that of Group A (P＜0.01).After intervention of EPO,mMSCs proliferation enhanced,at the same time,the apoptoic percentage decreased,in a dose-dependent manner.EPOR was positive in P3-mMSCs by Western blotting.EPO decreased the expression of caspase-3 in mMSCs under AKI microenvironment in a dose- and time-dependent manner,but increased the expression of Bcl-2.Cultured for 5 d,the expression of phosphor-Janus kinase2(p-JAK2) [(0.641 ±0.028) vs (0.456±0.012)] and phosphor-signal transducer and activator of transcription(p-STAT5)[(0.398±0.016) vs (0.209±0.020)] was significantly higher in 10 U/ml EPO group compared to group B.Conclusion Erythropoietin can promote proliferation of mMSCs in vitro under AKI microenvironment,which is mediated by EPOR and related with proliferation/apoptosis signal pathway.
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Objective To study curative effect of core decompression and autologous bone marrow stem cell transplantation combined with traditional Chinese medicine in the treatment of early femoral head necrosis (ANFH).Methods 30 patients with femoral head necrosis treated by different methods were divided into 3 groups: core decompression A group) 10 cases(12 hips) ;core decompression pus stem cells transplantation(B group) 10 cases(13 hips) ;core decompression pus stem cells transplantation combined with traditional Chinese medicine(C group) 10 ca-ses( 10 hips) ;The X-ray 、CT MRI、Harris score( HHS) .curative effect were observed.Results The phase of Ⅰ,Ⅱ,Ⅲ,in 3 groups didn't appear deformation and collapse at 3,6,12 months;The score of Harris after 12 months 93 points were higher than that preoperatively 57.5 points(χ 2= 5.81 ,P<0.05) ;The signal ratio of femoral head volume in MRI was 42% before treatment,disappearance of femoral head necrosis after treatment;Total curative effect of B,C group,werehighter than that Agroup(χ2 =3.81,χ2 =3.98,P<0.05).Conclusion The operative treatment of ANFH with core decompression and stem cells transplantation combined with traditional Chinese medicine had the advantage of minimal damage,simplicity,accuracy,and effectiveness.
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ObjectiveTo investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs)transplantation on acute myocardial infarction in swine models using MRI. MethodsFourteen Chinese mini-pigs(27±3 kg)were divided into control group(n=7)and transplantation group(n=7).Acute myocardial infarction(AMI)model was made by occlusion of the left anterior descending coronary artery for 90 minutes,and then 10 ml autologous MSCs(3 × 106 cell/ml)were injected into LAD by over-wire-balloon catheter after one week. MRl was performed to assess the cardiac function and myocardial perfusion 1 week after AMI and 6 weeks after transplantation.The implanted cells in vitro were analyzed by immunofluorescence.ResuitsThe left ventricular ejection fraction(LVEF)in transplantation group was increased from(42.7 ±7.5)%to(50.1±10.1)%,which was significantly different from that in control group(P＜0.01).In addition,the dyskinetic segments in infarcted region and the infareted area were decreased by 4 and 3.2 cm2 respectively(P＜0.01),and the left ventricular weight index was increased by 4.1 g/m2 in transplantation group(P＜0.05)compared with control group.The DAPI-labeled cells in infarcted and peri-infarcted region indicated the survived MSCs.Immunofluoreseence also confirmed that those cells expressed cardiomyocyte-specific troponin T,connexin 43 and vessel-specific smooth muscle actin.Capillary density in both infarcted and peri-infarcted region were higher in transplantation group than the control group(P＜0.01).Conclusion MRI is a reliable imaging method for assessing the effects of stem cell transplantation in acute myocardial infartion of swine models.
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@#ObjectiveTo investigate the clinical effects and side-effect of mesenchymal stem cell(MSCs) transplantation on spinal cord injury(SCI),traumatic brain injury(TBI),multiple sclerosis(MS) or Parkinson's disease(PD).MethodsThe bone marrow(222～350 ml) of 11 patients with SCI(n=6),TBI(n=3),MS(n=1) or PD(n=1) were harvested from the patients' ilia and then MNCs were isolated.The MNCs were injected intravenously or into subarachnoid space by lumbar puncture.The neural function and side-effect were observed before and after MSCs transplantation and the patients were followed up.ResultsThe data demonstrated the improvement of sense and motor function in 5 patients with SCI,one had no improvement by 2 months following-up.These patients' sense and motor levels improved obviously.Their muscle strength of lower extremity increased,the muscular tone decreased and urinary bladder function improved.Changes in neurological deficits and improvements in function may appear within 2 days after transplantation,most of them within 2 weeks.There were significantly amelioration in 3 patients with TBI treated with MSCs transplantation,one of them could walk with cane independently after 3 months.One's PVS score elevated from 5 to 8 scales after transplantation.The tremor was alleviated after 1 week,and the muscular tone decreased,which lead to reduce the dose of Madopar after 3 months,in patient with PD.The patient with MS showed no improvement in short time.The side-effect included fever(7/11),headache(2/11) and abdominal dissension(1/11).1 patient feel numb in his legs while injection into subarachnoid,and appeared meningeal stimulation after injection.ConclusionThere were significantly clinical effects in treatment of SCI,TBI,MS,and PD with MSCs transplantation in short time,and with few side-effect. The long-term clinical effects need more observation with larger samples.
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50%.Myocardial infarction(MI) models were created by ligating the distal left anterior descending artery in swines(n=18).Either BM-MSCs cells(5?106/mL)(n=6) or Ad5-HGF(4?109 pfu)(n=6) were transfused into infracted area via noninfarction-related artery at four weeks after MI.IMDM fluid was injected into the noninfarction-related artery in the control(n=6).Gate cardiac perfusion imaging was performed at four and seven weeks after LAD ligation respectively to evaluate the heart function and cardiac perfusion.Morphologic and histologic characteristics of the hearts were also studied.Results(1) New vessels firnation was found around the infarction area in all the three groups.By means of immno-histological staining,the density of capillaries and vessels with function in the BM-MSCs group and the Ad5-HGF group were 102.4?8.6/mm2 and 105.3?7.7/mm2,as well as 52.1?4.1/mm2 and 66.0?3.3/mm2 respectively.Both vessel density were higher than those of the control(55.5?4.7/mm2 and 16.4?3.5/mm2,P