Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury. Methods M...Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG+NSCs group received intracerebroventricular transplantation of NSCs (approximately 1.0×10^5 cells) separately on day 1 and day 10 after 10-d MSG exposure (4.0 g/kg per day). The mice in control and MSG groups received intracerebroventricular injection of Dulbecco's minimum essential medium (DMEM) instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.展开更多
The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model...The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.展开更多
AIM: To investigate apparent diffusion coefficient (ADC) values as an indication of reconditioning of acute hepatic injury (AHI) after allogeneic mononuclear bone marrow cell (MBMC) transplantation. METHODS: T...AIM: To investigate apparent diffusion coefficient (ADC) values as an indication of reconditioning of acute hepatic injury (AHI) after allogeneic mononuclear bone marrow cell (MBMC) transplantation. METHODS: Three groups were used in our study: a cell transplantation group (n = 21), transplantation control group (n = 21) and normal control group (n = 10). AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging (MR-DWI) and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS: At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group (27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000). The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group ((1.07± 0.07) ×10^-3 mm2/s vs (0.69 ± 0.05) ×10^-3 mm2/s, (1.41± 0.04) ×10^-3 mm2/s vs (0.84± 0.03) ×10^-3 mm2/s, (1.68 ± 0.04) ×10^-3 mm2/s vs (0.86± 0.04) ×10^-3 mm2/s, P = 0.000). The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [(1.07 ± 0.07) ×10^-3 mm2/s vs (± 0.03) ×10^-3 mm2/s, (0.69± 0.05) ×10^-3 mm2/s vs (1.76 ± 0.03) ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different (P = 0.000). At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk (P = 0.000). However, there was no significant difference between the 2nd and 4th wk (P = 0.073 and 0.473, respectively). The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 (P = 0.000) and -0.762 (P = 0.000) in the transplantation control group. CONCLUSION: Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.展开更多
Objective:To label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic bra...Objective:To label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury (TBI) by susceptibility weighted imaging (SWI)sequence.Methods:BMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley (SD) rats weighing 200-250 g were randomly divided into 4 groups: Groups A-D (n=6 for each group). Moderate TBI models of all the rats were developed in the left hemisphere following Feeney's method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day,one week and three weeks after implantation.Results: Numerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope (×200). Scattered little iron particles were observed in the vesicles by electron microscopy (×5000). MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images,phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.Conclusion:SWI sequence in vivo can consecutively and noninvasively trace and demonstrate the status and distribution of BMSCs labeled with SPIO in the brain of TBI model rats.展开更多
Acute respiratory distress syndrome (ARDS) remains a poor prognosis in spite of the recent development of new therapeutic strategies. Cell-based therapy with stem cells has been considered as a promising way for the...Acute respiratory distress syndrome (ARDS) remains a poor prognosis in spite of the recent development of new therapeutic strategies. Cell-based therapy with stem cells has been considered as a promising way for the treatment of vital organ damage. Putative endogenous stern cells have been shown to be located within the adult lung in the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, as well as within the alveolar epithelium. These stem cells are hypothesized to be the source of lung regeneration and repair. But this mechanism seems to be insufficient alter lung injury. There is increasing excitement over the last few years with the suggestion that exogenous stem cells may offer new treatment options for ARDS. Exogenous stem cells have the ability to differentiate and function as both airway and lung parenchymal epithelial cells in both in vitro and in- creasingly in vivo experiments. However, there is great controversy concerning the repair effect of adult stem cells in lung injury. This review evaluates the advances in endogenous respiratory stem cells, and assesses the evidence for the use of stem cells in the repair of lung injury.展开更多
Objective: To introduce a new animal model of graded mechanical primary brainstem injury (BSI). Methods: Altogether 45 rabbits were subjected to BSI by type II biological impact machine designed by the Third Mili...Objective: To introduce a new animal model of graded mechanical primary brainstem injury (BSI). Methods: Altogether 45 rabbits were subjected to BSI by type II biological impact machine designed by the Third Military Medical University. The animals were divided into 4 experimental groups (n=10) and 1 control group (n=5) ac- cording to different magnitudes of impact pressure imposed on the occipital nodule: Group 1,500-520 kPa; Group 2, 520- 540 kPa; Group 3,540-560 kPa; Group 4, 560-580 kPa and Group 5, 0 kPa with 20 kPa increase in each grade. The im- pact depth was a constant 0.5 cm. After injury, the clinical symptoms and signs as well as pathological changes were observed. Results: Rabbits in Group 1 revealed mild physiologi- cal reaction of BSI. They had localized cerebral contusion with punctate hemorrhage and subarachnoid hemorrhage (SAH) was limited to the peripheral tissues at the impact area. In Group 2, obvious physiological reaction was observed. Local pathological lesions reached the superfi- cial layer of brainstem tissues; focal hemorrhage and girdle- shaped SAH in basilar pon were observed under microscope. In Group 3, BSI was more severe with a long respiratory depression. Pathological lesions reached the inner portionof brainstem with massive hemorrhage and the whole brainstem was wrapped by subarachnoid hematoma. In Group 4, most rabbits died due to severe BSI. Pathological lesions deepened to the central brainstem with wide patho- logical change, rapture of the medulla oblongata central canal. Group 5 was the control group, with normal brainstem structure and no lesion observed. Conclusion: This model successfully simulates differ- ent levels ofbrainstem mechanical injury and clearly shows the subsequent pathological changes following injury. It takes two external parameters (impact pressure and depth) and has a similar injury mechanism to clinical accelerating BSI. Moreover it is reproducible and stable, thus being be- neficial for exploring pathophysiological mechanism, diag- nosis and forensic identification of various degrees of BSI.展开更多
Objective: To evaluate the efficacy and safety of the interventional techniques in the treatment of renal vascular injury. Methods: A total of 16 patients with renal vascular injuries were treated by superselective ...Objective: To evaluate the efficacy and safety of the interventional techniques in the treatment of renal vascular injury. Methods: A total of 16 patients with renal vascular injuries were treated by superselective arterial embolization. The renal injuries resulted from renal biopsy in 7 patients, endovascular intervention in 2, percutaneous puncture and pyelostomy in 2, local resection of renal tumor in 1 and trauma in 4. With regards to clinical manifestations, there was hemorrhagic shock in 8 patients, severe flank pain in 14, and hematuria in 14. CT and ultrasonography confirmed that 15 patients had perirenal hematoma. The embolization was performed with microcoils in 13 and standard stainless steel coils in 3 patients, associated with polyvinyl alcohol particles (PVA) in 9, and gelfoam particles in 6 cases. Results: Renal angiogram revealed arterlovenous fistula in renal parenchyma in 9 cases, pseudoaneurysm in 3 and extravasation of contrast media in 4. The arterial embolization was successful in all 16 cases in a single session. The angiography at the end of therapy showed that abnormal vessels had disappeared without other major intrarenal arterial branch occlusion. In 13 patients with hemodynamical compromise, blood loss-related symptoms were immediately relieved after blood transfusion. In 14 patients with severe flank pain, the pain was progressively relieved. Hematuria ceased in 14 patients 2-14 days after the embolization procedures. The renal function was impaired after the procedure in 6 cases, in which preoperative renal insufficiency was exacerbated in 3 and developed new renal dysfunction in 3, 2 of whom received hemodialysis. The ultrasonography showed that perirenal hematoma was gradually absorbed within 2-6 months after the procedure. All patients were followed up in 6-78 months (mean, 48 months). Six patients died of primary diseases (5 cases of renal failure and multiple organ failure and l case of malignant tumor). Ten patients survived without bleeding and further intervention. The deterioration of renal function did not occur and the serum creatinine and blood urea were in normal range. Conclusion: Transcatheter selective renal arterial embolization is a safe and effective method in the treatment of renal vascular injuries.展开更多
文摘Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG+NSCs group received intracerebroventricular transplantation of NSCs (approximately 1.0×10^5 cells) separately on day 1 and day 10 after 10-d MSG exposure (4.0 g/kg per day). The mice in control and MSG groups received intracerebroventricular injection of Dulbecco's minimum essential medium (DMEM) instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.
基金the National Basic Research Program of China(973Program),No.2007CB512705the General Program for Youths of the National Natural Science Foundation of China,No.30801464
文摘The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.
基金Supported by The National Natural Science Foundation of China,No. 30070235,No. 30470508 and No. 30870695The Natural Science Foundation of Hunan Province,No. 06JJ2008,07JJ6040
文摘AIM: To investigate apparent diffusion coefficient (ADC) values as an indication of reconditioning of acute hepatic injury (AHI) after allogeneic mononuclear bone marrow cell (MBMC) transplantation. METHODS: Three groups were used in our study: a cell transplantation group (n = 21), transplantation control group (n = 21) and normal control group (n = 10). AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging (MR-DWI) and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS: At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group (27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000). The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group ((1.07± 0.07) ×10^-3 mm2/s vs (0.69 ± 0.05) ×10^-3 mm2/s, (1.41± 0.04) ×10^-3 mm2/s vs (0.84± 0.03) ×10^-3 mm2/s, (1.68 ± 0.04) ×10^-3 mm2/s vs (0.86± 0.04) ×10^-3 mm2/s, P = 0.000). The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [(1.07 ± 0.07) ×10^-3 mm2/s vs (± 0.03) ×10^-3 mm2/s, (0.69± 0.05) ×10^-3 mm2/s vs (1.76 ± 0.03) ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different (P = 0.000). At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk (P = 0.000). However, there was no significant difference between the 2nd and 4th wk (P = 0.073 and 0.473, respectively). The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 (P = 0.000) and -0.762 (P = 0.000) in the transplantation control group. CONCLUSION: Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.
文摘Objective:To label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury (TBI) by susceptibility weighted imaging (SWI)sequence.Methods:BMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley (SD) rats weighing 200-250 g were randomly divided into 4 groups: Groups A-D (n=6 for each group). Moderate TBI models of all the rats were developed in the left hemisphere following Feeney's method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day,one week and three weeks after implantation.Results: Numerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope (×200). Scattered little iron particles were observed in the vesicles by electron microscopy (×5000). MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images,phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.Conclusion:SWI sequence in vivo can consecutively and noninvasively trace and demonstrate the status and distribution of BMSCs labeled with SPIO in the brain of TBI model rats.
文摘Acute respiratory distress syndrome (ARDS) remains a poor prognosis in spite of the recent development of new therapeutic strategies. Cell-based therapy with stem cells has been considered as a promising way for the treatment of vital organ damage. Putative endogenous stern cells have been shown to be located within the adult lung in the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, as well as within the alveolar epithelium. These stem cells are hypothesized to be the source of lung regeneration and repair. But this mechanism seems to be insufficient alter lung injury. There is increasing excitement over the last few years with the suggestion that exogenous stem cells may offer new treatment options for ARDS. Exogenous stem cells have the ability to differentiate and function as both airway and lung parenchymal epithelial cells in both in vitro and in- creasingly in vivo experiments. However, there is great controversy concerning the repair effect of adult stem cells in lung injury. This review evaluates the advances in endogenous respiratory stem cells, and assesses the evidence for the use of stem cells in the repair of lung injury.
基金The paper was supported by the National Natural Science Foundation of China,the Natural Science Foundation of Chongqing of China,the Key Projects Foundation of the Ministry of Public Security
文摘Objective: To introduce a new animal model of graded mechanical primary brainstem injury (BSI). Methods: Altogether 45 rabbits were subjected to BSI by type II biological impact machine designed by the Third Military Medical University. The animals were divided into 4 experimental groups (n=10) and 1 control group (n=5) ac- cording to different magnitudes of impact pressure imposed on the occipital nodule: Group 1,500-520 kPa; Group 2, 520- 540 kPa; Group 3,540-560 kPa; Group 4, 560-580 kPa and Group 5, 0 kPa with 20 kPa increase in each grade. The im- pact depth was a constant 0.5 cm. After injury, the clinical symptoms and signs as well as pathological changes were observed. Results: Rabbits in Group 1 revealed mild physiologi- cal reaction of BSI. They had localized cerebral contusion with punctate hemorrhage and subarachnoid hemorrhage (SAH) was limited to the peripheral tissues at the impact area. In Group 2, obvious physiological reaction was observed. Local pathological lesions reached the superfi- cial layer of brainstem tissues; focal hemorrhage and girdle- shaped SAH in basilar pon were observed under microscope. In Group 3, BSI was more severe with a long respiratory depression. Pathological lesions reached the inner portionof brainstem with massive hemorrhage and the whole brainstem was wrapped by subarachnoid hematoma. In Group 4, most rabbits died due to severe BSI. Pathological lesions deepened to the central brainstem with wide patho- logical change, rapture of the medulla oblongata central canal. Group 5 was the control group, with normal brainstem structure and no lesion observed. Conclusion: This model successfully simulates differ- ent levels ofbrainstem mechanical injury and clearly shows the subsequent pathological changes following injury. It takes two external parameters (impact pressure and depth) and has a similar injury mechanism to clinical accelerating BSI. Moreover it is reproducible and stable, thus being be- neficial for exploring pathophysiological mechanism, diag- nosis and forensic identification of various degrees of BSI.
文摘Objective: To evaluate the efficacy and safety of the interventional techniques in the treatment of renal vascular injury. Methods: A total of 16 patients with renal vascular injuries were treated by superselective arterial embolization. The renal injuries resulted from renal biopsy in 7 patients, endovascular intervention in 2, percutaneous puncture and pyelostomy in 2, local resection of renal tumor in 1 and trauma in 4. With regards to clinical manifestations, there was hemorrhagic shock in 8 patients, severe flank pain in 14, and hematuria in 14. CT and ultrasonography confirmed that 15 patients had perirenal hematoma. The embolization was performed with microcoils in 13 and standard stainless steel coils in 3 patients, associated with polyvinyl alcohol particles (PVA) in 9, and gelfoam particles in 6 cases. Results: Renal angiogram revealed arterlovenous fistula in renal parenchyma in 9 cases, pseudoaneurysm in 3 and extravasation of contrast media in 4. The arterial embolization was successful in all 16 cases in a single session. The angiography at the end of therapy showed that abnormal vessels had disappeared without other major intrarenal arterial branch occlusion. In 13 patients with hemodynamical compromise, blood loss-related symptoms were immediately relieved after blood transfusion. In 14 patients with severe flank pain, the pain was progressively relieved. Hematuria ceased in 14 patients 2-14 days after the embolization procedures. The renal function was impaired after the procedure in 6 cases, in which preoperative renal insufficiency was exacerbated in 3 and developed new renal dysfunction in 3, 2 of whom received hemodialysis. The ultrasonography showed that perirenal hematoma was gradually absorbed within 2-6 months after the procedure. All patients were followed up in 6-78 months (mean, 48 months). Six patients died of primary diseases (5 cases of renal failure and multiple organ failure and l case of malignant tumor). Ten patients survived without bleeding and further intervention. The deterioration of renal function did not occur and the serum creatinine and blood urea were in normal range. Conclusion: Transcatheter selective renal arterial embolization is a safe and effective method in the treatment of renal vascular injuries.