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Abstract Background: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. Case report: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related donor and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. Conclusions: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.
Resumen Introducción: La osteopetrosis es una displasia ósea hereditaria poco común, caracterizada por una actividad osteoclástica deficiente que aumenta la densidad mineral ósea. Se considera que el trasplante de células progenitoras hematopoyéticas (TCPH) puede revertir las anormalidades esqueléticas y restaurar la hematopoyesis. Caso clínico: Se presenta el caso de un paciente de sexo masculino, de 3 años y 2 meses de edad, con diagnóstico tardío de osteopetrosis. Se realizó un TCPH alogénico de donador relacionado 100% compatible con médula ósea. Se utilizaron un régimen de acondicionamiento mieloablativo y una dosis celular de CD34 de 4.7 × 107/kg de peso. En el postrasplante temprano, el paciente desarrolló complicaciones como neumonitis, hipercalcemia e hiperfosfatemia. Con un injerto granulocítico adecuado y quimerismo del 100% se consideró un trasplante exitoso. Sin embargo, el paciente presentó retraso en el injerto plaquetario, por lo que se administró factor estimulante de plaquetas por 6 meses. Actualmente el paciente se encuentra libre de enfermedad, en seguimiento ambulatorio, sin datos de enfermedad del injerto contra el hospedero y con pruebas de neurodesarrollo sin deterioro neurológico progresivo. Conclusiones: La osteopetrosis es una enfermedad infantil que requiere una sospecha clínica y un diagnóstico temprano, ya que es necesario un TCPH a corta edad como tratamiento para evitar la progresión de la enfermedad y el deterioro de las funciones neurosensoriales, hematológicas y endocrinológicas que puede derivar en la defunción del paciente.
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Child , Humans , Infant , Male , Osteopetrosis , Hematopoietic Stem Cell Transplantation , Osteopetrosis/genetics , Osteopetrosis/therapy , Follow-Up Studies , Chloride Channels , Transplantation Conditioning , MutationABSTRACT
Objective:To explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells(BMSC)on ischemia-reperfusion injury(IRI)in mice.Methods:A total of 30 C57BL/6 mice were randomly grouped into 6 groups of control, Norm-BMSC-exo, Hypo-BMSC-exo, IRI, Norm-BMSC-exo+ IRI and Hypo-BMSC-exo+ IRI.The model for IRI(25 min)was constructed.The serum levels of creatinine(Cr)and blood urea nitrogen(BUN)and histomorphology were examined at 24 h post-reperfusion.The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β)monocyte chemoattractant protein-1(MCP-1)and interleukin-10 (IL-10)were measured.The survival rate was observed for 7 days post-IRI.We also detected macrophage polarization glycolysis and oxidative phosphorylation(OXPHOS).Results:Compared with IRI group, Norm-BMSC-exo+ IRI group showed low levels of creatinine(Cr)and blood urea nitrogen(BUN)and mild pathological injury.The protective effects were enhanced in Hypo-BMSC-exo+ IRI group.BMSC-exo pretreatment could significantly improve the survival rate of mice post-IRI.Reverse transcription-polymerase chain reaction(RT-PCR)revealed that BMSC-exo significantly lowered the levels of TNF-α, IL-1β, MCP-1 and elevated the level of IL-10.BMSC exosomes polarized macrophage toward an M2 phenotype.And Hypo-exo could reprogramme macrophages to undergo a metabolic switch toward OXPHOS and away from glycolysis.Conclusions:Hypo-BMSC-exo could improve kidney injury via inducing M2 polarization in macrophages through promoting OXPHOS and suppressing glycolysis.
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In almost all human tissues and organs, adult stem cells or tissue stem cells are present in a unique location, the so-called stem cell niche or its equivalent, continuously replenishing functional differentiated cells. Those endogenous stem cells can be expanded for cell therapeutics using ex vivo cell culture or recalled for tissue repair in situ through cell trafficking and homing. In the aging process, inefficiency in the endogenous stem cell-mediated healing mechanism can emerge from a variety of impairments that accumulate in the processes of stem cell self-renewal, function, differentiation capacity, and trafficking through cell autonomous intrinsic pathways (such as epigenetic alterations) or systemic extrinsic pathways. This review examines the homeostasis of endogenous stem cells, particularly bone marrow stem cells, and their dysregulation in disease and aging and discusses possible intervention strategies. Several systemic pro-aging and rejuvenating factors, recognized in heterochronic parabiosis or premature aging progeroid animal models, are reviewed as possible anti-aging pharmaceutical targets from the perspective of a healthy environment for endogenous stem cells. A variety of epigenetic modifications and chromosome architectures are reviewed as an intrinsic cellular pathway for aging and senescence. A gradual increase in inflammatory burden during aging is also reviewed. Finally, the tissue repair and anti-aging effects of Substance-P, a peptide stimulating stem cell trafficking from the bone marrow and modifying the inflammatory response, are discussed as a future anti-aging target.
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Humans , Adult Stem Cells , Aging , Aging, Premature , Bone Marrow , Cell Culture Techniques , Cell Self Renewal , Epigenomics , Hematopoietic Stem Cells , Homeostasis , Models, Animal , Parabiosis , Rejuvenation , Stem Cell Niche , Stem CellsABSTRACT
ABSTRACT:Objective To investigate the bone marrow stem cell mobilization and homing changes of peripheral blood due to diabetic myocardial ischemia in rats and the change of expression of the vascular endothelial growth factor (VEGF)and the tumor necrosis factorα(TNFα)in ischemic myocardial tissue.Methods The diabetic model of male Sprague-Dawley rats was created by intraperitoneal injection of streptozotocin first.Then the diabetic myocardial ischemia model was established through ligation of the left anterior descending coronary artery. The rats were divided into ischemic day-1,day-3,day-7,and day-28 groups.And their time-matching diabetic sham operation control group and normal sham operation control group were also established,with 6 rats in each group. Flow cytometry was used to measure the percentage of CD34+ cells in peripheral blood mononuclear cells for each group.Immunohistochemistry was used to observe the homing of CD34+ cells and the expression of VEGF and TNFαin the ischemic myocardium.Results The mobilization of bone marrow stem cells was initiated after the surgery in the rat models of myocardial ischemia in diabetes and it peaked within 1 week and decreased with the passage of time.Accordingly the homing of CD34+ cells and the expressions of VEGF and TNFαin the ischemic myocardium were significantly increased.Conclusion During the early stage,the diabetic ischemic myocardium can mobilize bone marrow stem cells into the peripheral blood and start homing to the ischemic myocardium by increasing VEGF and TNFαin the ischemic myocardium,thereby initiating the self-protection mechanisms.
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Objective Our research aimed to investigate the efficacy and the nursing characteristics of allogenic bone marrow mesenchymal stem cell (BM-MSCs) transplantation in HBV related acute-on-chronic liver failure (ACLF) patients.Methods A total of 91 HBV related ACLF patients were enrolled,among whom 45 patients received allogenic BM-MSCs transplantation via peripheral vein and other 46 patients received medical treatment only.We assessed the 12-week survival rates and the variation of model for end liver disease (MELD) score.Besides,we administrated comprehensive nursing for these patients in different stages of the transplantation.Results The cumulated survival of patients received BM-MSC transplantation was 75.6％,which was higher than the control group (54.5％).The level of total bilirubin and International Normalized Ratio (INR) had greatly improved.41 of 45 patients passed through perioperative period safely,without any severe adverse events.11 patients died due to exacerbation of liver failure,among whom 3 happened in perioperative period.But none was related with the operation.Conclusions Allogenic BM-MSCs transplantation can improve the survival rate of HBV related ACLF patients.The psychological nursing pre-operation,skilled operation,intensive care and observation post operation were beneficial to the patients' recovery after transplantation.
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Objective To observe the effect of injectable tissue-engineered bone in treating periarticular bone fracture nonunion under arthroscopy. Methods Selected 6 patients with intra-articular bone fracture nonunion:3 cases of humerus intercondylar fracture;2 cases of femoral condylar fracture and 1 cases of tibial plateau fracture. All of the 6 patients have undergone arthroscopic debridment and tissue-engi-neered bone injection in the the fracture ends with puncture needle under direct vision. Percutaneous needle internal fixation were performed if necessary. All the patients have got regular follow-up after the operation process. Check their healing condition with X-ray examination, and the healing of the bone and its complications have also been monitored. Reexamination were made 3, 6, 9, and 12 months after surgery. Results All the patients have experienced successful operation and all the fracture have healed up. The X-ray review showed that the callus healing time was (8. 34 ± 2. 4) weeks and fracture healing time was (18. 2 ± 3. 3) weeks. Accordong to Johner-Wruhs functional category, there were 5 cases of excellent recovery and 1 case of medium recovery. Among these patients, inflammatory reaction occurred in 1 case, and the symptoms disappeared after 2 weeks of Vancomycin anti-inflammatory treatment; deep venous thrombosis occurred in 1 case, and the symptoms disappeared after systematic anticoagulant therapy. Conclusion It’ s safe and effective to treat periarticular bone fracture nonunion with injectable tissue-engineered bone under arthroscopy.
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Objective To investigate the clinical efficacy of Shenmai injection (SMI) combined with heart transplantation of autologous bone marrow stem cells in the treatment of refractory heart failure(RHF). Methods Two hundred patients with RHF were selected from the Emergency Department of the First Affiliated Hospital of Zhengzhou University and the Cardiology Department of the First Affiliated Hospital of Henan College of Traditional Chinese Medicine. They were randomly divided into control group and treatment 1,2 and 3 groups(each 50 cases). In the control group,heart failure standard treatment was given;group 1 received a standard treatment for heart failure combined with autologous bone marrow stem cell heart transplantation;group 2 received a standard treatment for heart failure with SMI;group 3 received a standard treatment for heart failure combined with autologous bone marrow stem cell heart transplantation and SMI. The mean follow-up was 24 months. The prognosis,readmission rate,clinical efficacy,cardiac function and the change in levels of B-type natriuretic peptide(BNP)of patients in each group were observed during the therapeutic course and observation period. Results During the course of treatment,there were 10 cases dead in the control group,4 in each group 1 and 2 respectively,and 3 in group 3. Readmission rates in group 1,2 and 3 were significantly lower than that in control group(38%,36%,24%vs. 48%, P<0.05 or P<0.01). The rates of total efficiency in group 1,2 and 3 were obviously higher than that in the control group(88%,86%,94%vs. 76%,all P<0.05). After treatment,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(FS)and left ventricular end-systolic diameter(LVESD)in three therapeutic groups were significantly higher than those before treatment,while the left ventricular end-diastolic diameter(LVEDD)and BNP level were significantly lower than those before treatment. All the above indexes in three therapeutic groups after treatment were much more remarkably improved than those in the control group during the same period,and the group 3 being the most significant〔LVEF:0.477±0.099 vs. 0.396±0.098,FS:(30.0±5.1)%vs.(26.8±7.5)%,LVESD (mm):40.6±9.1 vs. 45.8±9.4,LVEDD(mm):44.9±9.8 vs. 52.8±10.1,BNP(ng/L):515±400 vs. 1 875±400, all P<0.05〕. Conclusion SMI combined with heart transplantation of autologous bone marrow stem cells has obvious therapeutic effect for treatment of RHF.
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Objective To investigate the mobilization of granulocyte-colony stimulating factor(G-CSF) with stem cell factor(SCF) in bone marrow stem cells(BMSC),and to observe the therapeutic effects of BMSC mobilization on repairing ischemia/reperfusion(I/R) renal injury induced by hypoxia inducible factor-1α (HIF-1α) and epidermal growth factor(EGF),and to investigate the mechanism for BMSC mobilization for repairing I/R renal injury.MethodsOne hundred and sixty male Sprague-Dawley rats(age:8-10 weeks) were randomly allocated into 4 groups(40 rats in each group):control group (group A),I/R group(group B),SCF + G-CSF treatment group (group C) and SCF + G-CSF control group(group D).The expressions of CD34 + and EGF were measured by immunohistochemistry technique,and the expression of EGF mRNA was measured by reverse transcriptase-polymerase chain reaction.Results 1.After I/R injury,the renal tubular epithelial cells were in a state of degeneration,necrosis,even exfoliation.As the time prolonged,the necrotic renal tubules were repaired gradually,but the repair in group C was not good compared with that in group B.The level of group C was obviously lower than that of group B on the 5th,10th,17th and 24th day(P ＜ 0.05).2.There was no significant difference in the percentage of CD34 + cells between group A and D(P ＞ 0.05).On 5 d postoperative,the level of CD34 + cells of group B and group C was conspicuous higher than group A and D (P ＜ 0.05),and that of group C was conspicuous higher than that of group B (P ＜ 0.05).They descended gradually from the 5 th day with the time prolonged.3.The expressions of HIF-1c of group B and group C had a highly positive reaction on the 5th day postoperatively and the level of HIF-1α of group B and group C decended to the normal level with the time prolonged,and at each time,the expression of HIF-1α of group C was significantly higher than that of other groups (P ＜ 0.05).4.On the 5th day postoperative,the expression of EGF of group B and group C showed a higher positive reaction on the 5th day postoperatively and the level of EGF in group B and group C descended to the normal level with the time prolonged,and at each time the expression of EGF of group C was significantly higher than that of the other groups (P ＜0.05).5.The expressions of EGF mRNA of group B and C showed higher positive reaction on the 5th day postoperatively(P ＜ 0.05).The level of EGF mRNA of group B was higher significantly than that of group A on the 17th day postoperatively(P ＜ 0.05).The level of EGF mRNA of group C was a peak and higher than that of other groups on the 10th day postoperatively(P ＜ 0.05).The level of EGF of group B and group C descended to a normal level with the time prolonged.6.There was a positive correlation between the expressions of HIF-1α and EGF (r =0.815,P ＜ 0.01).Conclusions Combination of SCF with the mobilization of G-CSF sufficiently homed BMSC to injured renal tissue was an important factor for the recovery of injured renal tubules.Combination of SCF with G-CSF may promote the expression of HIF-lα and EGF in the kidney may be one of the mechanisms of why combination of SCF with G-CSF can promote recovery from renal ischemic reperfusion injury.
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BACKGROUND AND OBJECTIVES: Hydroxyapatite has biocompatibility and bioactivity and similar to bone of in human body. The purpose of this study is to evaluate osteogenic differentiation of bone marrow stem cell (BMSC) in PLGA Scaffold added various ratio of hydroxyapatite (HAp). METHODS AND RESULTS: PLGA and PLGA/HAp scaffold were prepared using solvent casting/salt-leaching method. BMSC was seeded on the PLGA and PLGA/HAp scaffold and the samples were cultured in 37degrees C incubator with 5% CO2 for 28 days. Alkaline phosphatase (ALP) was carried out to evaluate alkaline phosphatase activity at 1, 3, 7, 10 and 14 days. Alizarin Red S stating was performed to identify calcium in scaffold at 1, 7, 14, 21 and 28 days. Compressive strength was measured to evaluate mechanical property of scaffold. To confirm cell viability, MTT was carried out at 1, 3, 7, 14 and 28 days. RT-PCR was performed to verify specific marker expression of osteoblast and stem cell at 7, 14, 21 and 28 days. CONCLUSIONS: Osteogenic differentiation of BMSC was confirmed through ALP, RT-PCR, and alizarin red S staining in this study. These results suggest that HAp helps osteogenic differentiation of BMSC.
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Alkaline Phosphatase , Anthraquinones , Bone Marrow , Calcium , Cell Survival , Compressive Strength , Durapatite , Human Body , Incubators , Lactic Acid , Osteoblasts , Polyglycolic Acid , Seeds , Stem CellsABSTRACT
Objective To investigate mobilization of the bone-marrow-derived stem cell (BMSC) into peripheral blood by granulocyte-colony stimulating factor (G-CSF) to accelerate the renal regeneration.Methods Six-week-old transgenic C57BL/6J mice labeled with green fluorescent protein (GFP) as bone marrow donors and C57BL/6 mice without fluorescence label as recipients ( n =20 ) of bone marrow transplantation were used.All recipients received lethal dose of 8.5 Gy total body γ-ray irradiation with 137 Cs before bone marrow transplantation,and the transplantation of bone marrow mononuclear cells 2 × 105 by retrobulbar injection was done two hours later after irradiation. Bone marrow reconstruction after transplantation was proved by flow cytometry five weeks after transplantation.Six weeks after the bone marrow reconstruction completed,left renal pedicles of all mice were cross-clasped for 30 minutes followed by reperfusion to establish the animal model of ischemia-reperfusion injury.Mice were divided into two groups:( 1 ) Saline control group ( n =10),saline 0.2 ml/day was injected subcutaneously into chimeric mice from 3 days before to 4 days after operation ; (2) G-CSF mobilization group (n =10),chimeric mice were injected subcutanously with recombinant human G-CSF,200μg/kg/day,once a day from three days before surgery for a week.On the 1st day after mobilization,the percentage of stem cell in non-erythroid cells of peripheral blood was detected by using flow cytometry.One week after ischemia,the homing of BMSC to kidney was identified by flow cytometory.Renal tissue sections were stained with Hemotoxylin and Eosin staining method for pathological study,and the degree of renal tubular injury was analyzed by semiquantitative method of Vyacheslav.Four weeks after ischemia,the differences in degree of renal regeneration between the two groups by analysis the numbers of vascular endothelial cells in the kidney.Results After G-CSF mobilization,the percentage of stem cells with Sca-1 +,c-Kit +,CD29 and CD34 + antigen in peripheral blood in G-CSF mobilization group were higher than those in control group.One week after ischemia,mice of mobilization group showed higher percentage of Sca-1 +,c-Kit + and CD34 + bone marrow derived stem cells in tbe kidney compared to control group (P ＜0.05).One week after ischemia,the tubular epithelial damage score of mobilization group was lower significantly than that of the control group (P ＜ 0.05 ) studied by Hemotoxylin and Eosin staining. Four weeks after ischemia,mice of G-CSF mobilization group showed more CD31 positive cells in the kidney compared to control group (P ＜ 0.05 ).Conclusions G-CSF can effectively mediate the mobilization of bone marrow derived stem cells to peripheral blood and homing to kidney.G-CSF mobilization can accelerate renal regeneration and alleviate the degree of renal histopathological changes after ischemia.
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Bone marrow stem cells (BMSCs) are a type of self-renewing,multipotential stem cell group that mainly locate in bone marrow.Due to their great expansion,seLf-renewing and the potential ability of differentiating into a wide variety of cell types,BMSCs have become ideal target cells of tissue engineering,cell transplantation and gene therapy.The ophthalmology-related BMSCs research is primarily focused on the therapy of the corneal diseases and retinal diseases.The therapy of the retinal diseases include vitreous cavity injection and subretina transplantation.Both of them get some exciting effectiveness.However,less reports of the application of BMSCs in optic nerve diseases are seen up to now.The research about BMSCs provides a new clue for solving the modern ophthalmology diseases.But the research remains still in an animal experiment stage.Many relevant problems need to solve prior to its going into clinical trial.This review sumumarized the development,characteristics and prospect of BMSCs.
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PURPOSE: To evaluate the degree of biological healing response that occurs between the anterior horn of the medial meniscus (MM) and the tibial plateau and investigate the biological healing response after injection of human bone marrow stem cells (hBMSCs) in a rabbit model. MATERIALS AND METHODS: Twenty-five rabbits with a mean body weight of 2.5 kg were chosen for this study. On the left knee, a complete radial tear was made at the anterior tibial attachment site of MM and after removal of tibial cartilage, pullout repair of the torn MM was performed on the tibial plateau. On the right knee, the same procedure was performed, and a scaff old (matrix gel) that contained human bone marrow stem cell was implanted between MM and the tibial plateau. A biopsy was performed at 2 (group 1), 4 (group 2), and 8 (group 3) weeks postoperatively. The authors compared the differences in the degree of biological healing of each group and investigated the degree of biologic healing after hBMSC implantation by comparing the left knee with the right knee. RESULTS: On the biopsy of 40 knees of 20 rabbits that survived after operation, all groups did not show the healing response between the undersurface of MM and the tibial plateau. There was no significant difference in terms of the pathological criteria such as fibroblasts and fibrochondrocytes etc., with and without hBMSC implantation. CONCLUSIONS: There was no attachment between the repaired MM and the tibial plateau after complete radial tear on MM and the authors could not identify the effect of hBMSC.
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Animals , Humans , Rabbits , Biopsy , Body Weight , Bone Marrow , Cartilage , Fibroblasts , Horns , Knee , Menisci, Tibial , Stem CellsABSTRACT
Objective To study portal vein hemodynamics changes after autoiogous bone marrow stem cell transplantation in patients with liver cirrhosis. Methods The hemodynamic parameters, including portal vein diameter, average portal blood flow velocity and spleen size, were determined by Colour Doppler Ultrasonography in 50 patients after autologous bone marrow stem cell transplantation and all cases were followed for up to 6 months. Results (1) After autologous marrow stem cell transplantation, the portal vein diameter reduced significantly at different timepoints compared to before the treatment ([1.41 ± 0. 15] cm, [1. 38 ± 0. 11]cm,[1.36±0. 17] cm vs. [1. 53 ±0. 18] cm,t = 1. 987,1.994,1. 976, Ps 0.05). (2) After autologous marrow stem cell transplantation, the average portal blood flow velocity increased significantly at different timepoints compared to before the treatment ([15. 7 ± 3. 6] cm/s, [16. 1 ± 2.4] cm/s, [15. 9 ± 3.0] cm/s vs.[11.4 ± 3. 3] cm/s ,t = 2. 345, 2.460,2. 381, Ps 0.05) . (3) After autologous marrow stem cell transplantation,the spleen size reduced significantly at different timepoints compared to before the treatment ([4.8±0.3]cm,[4.7±0.6]cm,[4.8±0.5]cm vs. [5. 2 ±0. 7]cm,t =2. 289,2. 390,2.425,Ps 0.05) .Conclusion The autologous bone marrow stem cell transplantation can effectively improve the portal vein blood flow,reduce the spleen size,alleviate portal hypertension in patients with liver cirrhosis.
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Objective To summarize the nursing experience of treatment of percutaneous and transhepatic portal venous autologous bone marrow stem cell transplantation for chronic hepatic failure.Methods 19 patients who were definitely diagnosed as chronic liver failure received pertinent nursing in different perioperative period of transhepatic portal venous autologous bone marrow stem cell transplantation.Results All of the 19 patients went through perioperative period safely without any adverse reactions or complications.Conclusions In the process of treatment of autologous bone marrow stem cell transplantation for chronic hepatic failure,sufficient preoperative preparation,good communication and close cooperation among doctors,nurses and patients during operation,careful nursing and rehabilitation instruction after operation,are important assurances for autologous bone marrow stem cell transplantation to run smoothly.
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@#Objective To investigate the clinical effect of percutaneous autogenous bone marrow stem cell transplant on bone nonunion. Methods 140 patient with bones nonunion were divided into the autogenous bone transplants (A) group and the autogenous bone marrow stem cell transplant (B) group, with 70 cases in each group. They were assessed 2 and 5 months after operation. Results A few calluses could be observed at the end of fracture in 42 cases in group A 2 months after operation, and massive callus formation could be observed in 46 cases 5 months after operation. However, massive callus formation could be observed in 60 cases in group B 2 months after operation, and continual callus formation could be observed in 45 cases 5 months after operation. The mean healing time was (8.4±1.8) months in group A, and (6.5±2.0) months in group B (P<0.05). No side-effects have been observed during the treatment. Conclusion The percutaneous autogenous bone marrow stem cell transplant is more effective on bone nonunion compared with the traditional treatment.
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Objective:To observe effects of Panax pseudo-ginseng saponins on protein expression of VEGF, bFGF in myocardium in acute myocardial infarction rats. Methods: The acute myocardial infraction (AMI) model was established in one hundred and forty Wistar rats, and the rats were randomly divided into five groups: the western medicine group mobilized by subcutaneous injection of G-CSF50?g.kg-1.d-1, sham-operated group and model group treated by subcutaneous injection of normal saline 50?g.kg-1.d-1, the Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong (ingredients of Panax pseudo-ginseng saponins) 150mg.kg-1.d-1, the integrative group mobilized by subcutaneous injection of G-CSF 50?g.kg-1.d and intraperitoneal injection of Xuesaitong 150mg.kg-1.d-1. Except for the sham-operated group, each group was divided into three sub-groups by three time points of 1d, 7d and 14d. G-CSF was used once a day for 7 days. Xuesaitong was injected once a day until the rats were killed. The parameters cardiac function in rats with myocardial infarction were detection by color doppler ultrasonic diagnostic apparatus in different times,the expression of VEGF, bFGF in Marginal zone of myocardium in rats with myocardial infarction were detected by immunohistochemistry in different time. Pathological and ultrastructural changes of marginal zone in rats with acute myocardial infarction were observed by electron microscopy and light microscopy. Results:Panax pseudo-ginseng saponins can improve the level of left ventricular systolic function such as EF,FS,it can inhibit the increase of left ventricular LVDD and LVDS,it can improve expression levels of VEGF,bFGF of marginal zone in acute myocardial infarction rats. It also can reduce the damage to cell ultrastructure and promote revascularization in the site around MI area. Panax pseudo-ginseng saponins can protect the myocytes in rats with myocardial infarction. Conclusion:Panax pseudo-ginseng saponins can protect myocardium from ischemic injury in rats after AMI by way of improving expressions of VEGF and bFGF in myocardial cells and promoting angiogenesis in the infarcted of myocardium.
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The role of cultured bone marrow stromal cells (BMSCs) in peripheral nerve regeneration was examined using an established rabbit peroneal nerve regeneration model. A 15-mm peroneal nerve defect was bridged with a vein filled with BMSCs (1 x 10(6)), which had been embedded in collagen gel. On the contralateral side, the defect was bridged with a vein filled with collagen gel alone. When the regenerated tissue was examined 4, 8 and 12 weeks after grafting, the number and diameter of the myelinated fibers in the side with the BMSCs were significantly higher than in the control side without the BMSCs. This demonstrates the potential of using cultured BMSCs in peripheral nerve regeneration.
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Bone Marrow , Collagen , Mesenchymal Stem Cells , Myelin Sheath , Peripheral Nerves , Peroneal Nerve , Regeneration , Transplants , VeinsABSTRACT
Objective To evaluate the efficacy and safety of transplantation of autologous bone marrow mesenchymal stem cells (BMSCs) and mononucleus cells (BMMNCs) for treating coronary heart disease. Methods Ten patients who had suffered from coronary heart disease with myocardial infarction, were selected. In 7 patients BMSCs+BMMNCs were transplanted immediately following PCI and 3 patients only accepted transplantation of BMSCs+BMMNCs without PCI. Autologous BMSCs+BMMNCs were isolated and cultured for 2-3 weeks. And (0.9～3.5)?106 BMSCs+1.6～6.1?106 BMMNCs were transplantated through intracoroary way. Cardiac functions were determined by 2-D echocardiography、 technetium- 99m methoxyisobutylisonitrile ( 99m Tc-MIBI) and ECG Holter monitor before and 6 months after the procedure. Results Left ventricular ejection fraction (LVEF) was significantly increased by 10.5% (4.0%-18.0%) and left ventricular diastolic diameter(LVDd) reduced by 2.2 mm (-4 mm-8 mm) and neither obvious arrhythmia nor complication was observed during the 6-12 months′ follow up in all the 10 patients. Conclusion The preliminary study showed that in the patients who suffered from coronary heart disease complicated with myocardiac infarction, transplantation of BMSCs+BMMNCs could improve cardiac function and cardiac perfusion without significant complication and arrhythmia during the 6-12 months′ follow-up.
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Objective To investigate the possibility of immune tole rance induced by bone marrow-derived mesenchymal stem cells in allogeneic organ transplantation. Methods Allogeneic bone marrow-derived mesenchymal stem cells and syngeneic bone marrow cells were cotransplanted to lethally irradiated female C57BL/6 recipient mice. FACS was used to analyze the chimerism 150 days later. Mixed lymphocyte reaction and ConA induced proliferation test were performed to evaluate proliferative activity of mice spleen cells in cell-transplanted group. Skin transplantation test was done to observe immune response of cell-transplanted group mice against organ graft from donor mice. Results About 5 97% donor T cells were detected in splenocytes of cell-transplanted group mice. MLR showed that mean SI of cell-transplanted group mice was 1.79, and that of untreated group mice was 7 28. ConA induced proliferation test showed that mean SI of cell-transplanted group mice was 31 92; and that of untreated group mice was 34 99. Mean survival time of donor-derived skin graft in cell-transplanted group mice was more than 90 days; and that in untreated group mice was 8 days. Conclusion Our results showed for the first time that induction of stable mixed hematopoietic chimerism after allogeneic bone marrow derived mesenchymal stem cells transplantation lead to stable donor-specific tolerance in allogeneic host and skin graft survival from donor mice.
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Objective:To explore the effect of bone marrow stem cell mobilization in resolution of deep vein thrombosis.Methods:The SD adult rats were randomly divided into normal,sham,surgical and mobilization group(with subcutaneous injection of rhG-CSF).The peripheral blood mononuclear cell count,pathological change and thrombus organization rate in different time were examined.Results:The peripheral blood mononuclear cell count in mobilization group was significantly elevated,and there was no significant change in other groups.Compared with surgical group,there were more inflammatory cells in thrombus of mobilization group at 7th postoperative day,and the organization area of thrombus was wider and the organization rate was significantly different in mobilization group at 14th postoperative day(P