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OBJECTIVE@#To study the effect of human oligodendrocyte precursor cell (hOPC) transplantation in the treatment of white matter injury (WMI).@*METHODS@#Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group (@*RESULTS@#The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency (@*CONCLUSIONS@#Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.
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Animals , Humans , Rats , Animals, Newborn , Myelin Sheath , Oligodendrocyte Precursor Cells , Oligodendroglia , White MatterABSTRACT
BACKGROUND: Adipose-derived stem cells (ADSCs) can establish a favorable repair microenvironment by secreting abundant cytokines, which allows ADSCs to be a good source of seed cells for the treatment of ischemic diseases. OBJECTIVE: To investigate the changes of cytokines secreted by human ADSCs at passages 2-10. METHODS: After isolation and culture of ADSCs from human adipose tissue, the morphological features of cells were observed under inverted microscope. Human ADSCs were identified by the immunophenotypes and differentiation capability. RESULTS AND CONCLUSION: ADSCs were fusiform or polygonal in shape, with buging cell body, homogenized cytoplasm and clear nuclei, and could differentiate into adipocytes, osteocytes and chondroblasts in vitro. ADSCs at passage 3 were positive for CD29 (99.21%), CD73 (99.65%) and CD90 (99.92%), but negative for hematopoietic marker CD34 (2.25%). ELISA results showed that ADSCs at passage 5 had the highest secretion levels of vascular endothelial growth factor and hepatocyte growth factor, while ADSCs at passage 3 had the highest secretion level of brain-derived neurotrophic factor. To conclude, ADSCs have steady biological features of stem cells and exhibit good growth and proliferation potentials. ADSCs at different passages have different capacities in the secretion of vascular endothelial growth factor, hepatocyte growth factor and brain-derived neurotrophic factor. Passage 5 ADSCs show the highest ability to secrete vascular endothelial growth factor and hepatocyte growth factor, while passage 3 ADSCs show the strongest potential to secrete brain-derived neurotrophic factor.
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Objective To investigate the effects of autologous and allogeneic adipose derived mesenchymal stem cells (ADMSCs) transplantation on rat model of acute myocardial infarction (AMI) and possible mechanisms.Methods The AMI models were established with 45 male Lewis rats by ligation of left anterior descending coronary artery,and then randomly divided into 3 groups (15 each) including AMI group,allogeneic ADMSC transplantation group (Allo-ADMSC group) and autologous ADMSC transplantation group (Auto-ADMSC group).After successfully modeling,CM-Dil-labeled third-generation ADMSCs (2 × 106) were implanted into the myocardium of rats within 1 hour,and rats in AMI group were injected with equal amount of PBS.The cardiac function,immunofluorescence and Masson were identified 4 weeks after transplantation.Results Four weeks after transplantation,compared with AMI group,the left ventricular ejection fraction in Allo-ADMSC group and Auto-ADMSC group increased significantly,the left ventricular end-systolic and end-diastolic diameter decreased,the collagen deposition fraction decreased significantly (P＜0.05).Compared with Allo-ADMSC group,the left ventricular ejection fraction increased in AutoADMSC group,the number of newborn capillaries increased and the myocardial collagen deposition fraction decreased (P＜0.05).Conclusion Autologous ADMSC can promote vascular proliferation in the infarct area more better than allogeneic ADMSC,reduce the local collagen deposition,extenuate the degree of myocardial fibrosis,thereby to inhibit collagen remodeling,and repair damaged myocardial tissue and improve heart function.
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BACKGROUND:Endothelial progenitor cells are precursor cells of mature endothelial cells,which can migrate to ischemic tissues and differentiate into mature endothelial cells,and then play an important role in vascular remodeling.Endothelial progenitor cells have wide application prospects in various ischemic diseases,but the biological characteristics and identification methods are still controversial.OBJECTIVE:To investigate the methods of isolation and culture of endothelial progenitor cells from the human adipose tissue and to identify their biological features,in order to provide a sufficient source of cells for ischemic diseases.METHODS:Stromal vascular fraction cells were isolated from the human adipose tissue by enzymatic digestion,CD31+ cells were selected using immunomagnetic beads,and then cultured in endothelial basal medium-2 supplemented with the EGM-2-MV-SingleQuots.Endothelial progenitor cells were identified through detection of morphology,cell markers and cell functions.RESULTS AND CONCLUSION:(1) CD31 + cells were selected by immunomagnetic beads and then cultured and amplified in vitro,which displayed typical cobblestone-like morphology,and they maintain their proliferative ability.(2) Flow cytometry results showed that the CD31+ cells expressed CD31 (98.84％),CD34 (97.21％),VEGRR2 (64.07％),CD146 (98.42％) and CD133 (2.55％),but hardly expressed CD45 (1.1％),a hematopoietic stem cell marker.(3) The CD31 + cells were also found to incept Dil-ac-LDL and exhibit lectin binding capability.Furthermore,a lumen-like structure was formed in Matrigel,which has the ability of angiogenesis in vitro.To conclude,these results suggest that it is feasible to isolate and culture endothelial progenitor cells from the human adipose tissue by enzymatic digestion combined with immunomagnetic bead sorting.
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<p><b>OBJECTIVE</b>To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant.</p><p><b>METHODS</b>A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×10OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days.</p><p><b>RESULTS</b>Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P<0.05).</p><p><b>CONCLUSIONS</b>OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.</p>
Subject(s)
Animals , Rats , Animals, Newborn , Disease Models, Animal , Myelin Sheath , Pathology , Oligodendrocyte Precursor Cells , Transplantation , Rats, Sprague-Dawley , White Matter , Wounds and Injuries , PathologyABSTRACT
<p><b>OBJECTIVE</b>To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.</p><p><b>METHODS</b>Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later.</p><p><b>RESULTS</b>No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05).</p><p><b>CONCLUSIONS</b>These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.</p>
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Child , Child, Preschool , Female , Humans , Male , Child Development Disorders, Pervasive , Therapeutics , Neural Stem Cells , Transplantation , Rett Syndrome , TherapeuticsABSTRACT
This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.