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BACKGROUND:The endothelial dysfunction is the pathogenesis of arteriosclerotic disease, the quantity and function of endothelial progenitor cells are decreased within the cycle, leading to a poor capacity of neovascularizatio, the efficacy of stem celltransplantation alone is unclear, the combination of cytokines and gene-modified stem cells is the hotspot. OBJECTIVE:To observe the effect of stromal cel-derived factor-1 on the neovascularization after endothelial progenitor cells transplantation. METHODS:Unilateral hindlimb ischemia model was established in 20 athymic nude mice, and the mice were randomly divided into four groups:combined group (intravenous endothelial progenitor cells+intramuscular stromal cel-derived factor-1), endothelial progenitor cells group (intravenous injection of endothelial progenitor cells), stromal cel-derived factor-1 group (intramuscular injection of stromal cel-derived factor-1), and blank control group (intramuscular M199). The skin temperature of ischemic hindlimbs and survival of animals after transplantation were observed. The ratio of capil ary/skeletal muscle fiber was counted. The expression of CD31 and endothelial nitric oxide synthase were detected. RESULTS AND CONCLUSION:The fluorescence-labeled endothelial cells were embedded in ischemic hindlimb muscles after celltransplantation. Of the 20 nude mice, two mice died. The rate of ischemic hindlimb reserving was respectively 80%, 75%, 20%and 0 in combined group, endothelial progenitor cells group, stromal cel-derived factor-1 group, and blank control group. The capil ary/muscle fiber ratio in combined group and endothelial progenitor cells group was higher than that of blank control group (P0.05). Endothelial progenitor cells can migrate to ischemic tissues, endothelial progenitor cells transplantation can promote neovascularization, and stromal cel-derived factor-1 augments the neovascularization after celltransplantation, in which endothelial nitric oxide synthase is involved.
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BACKGROUND:Adipose-derived stem cels are a population of multilineage cels isolated from adipose tissue, which may have a positive effect on the treatment of ischemic diseases. OBJECTIVE:To explore the therapeutic and angiogenic effects of adipose-derived stem celsvia local transplantation on random pattern skin flaps in mice. METHODS: Human adipose-derived stem cels were isolated, cultured and passagedin vitro. On the back of the SPF mice, random pattern skin flaps were performed. After the operation, the adipose-derived stem cels were injected into the pedicle, central, and distal end of the flaps in the experimental group, while only PBS was injected into the control flaps. Seven days later, the survival rate of flaps was evaluated. Immunofluorescence assay was preformed to observe the distribution of microvessels in the flaps and trace the CM-Dil labeled adipose-derived stem cels, while the level of vascular endothelial growth factor was tested by ELISA and the protein expression of stromal cel-derived factor 1 tested by western blot at day 14 after adipose-derived stem cels transplantation. RESULTS AND CONCLUSION:Compared with the control group, there was a significant increase in the flap survival rate in the experimental group, and along with the sharply increased number of microvessels, the secretions of vascular endothelial growth factor and stromal cel-derived factor 1 were also obviously raised in the experimental group (P < 0.05). After local transplantation of adipose-derived stem cels into random skin flaps, it could intervene the secretion of vascular endothelial growth factor and stromal cel-derived factor 1 and promote angiogenesis of the skin flap.
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BACKGROUND:Umbilical cord mesenchymal stem cels have strong proliferation and differentiation capacities, and can be induced to differentiate into pancreatic β cels, thereby playing a therapeutic effect on diabetes mel itus. OBJECTIVE:To study the therapeutic effects of transplantation of umbilical cord mesenchymal stem cels for treatment of diabetes melitus in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into control group (n=6), transplantation group (n=12) and diabetic group (n=12). Rats in the control group were given normal saline injection. Rats in the other two groups were injected with streptozotocin at a dose of 45 mg/kg to establish diabetic models. After modeling, transplantation of umbilical cord mesenchymal stem celsviatail vein was given in the transplantation group. RESULTS AND CONCLUSION:Thirty days after modeling, the fasting blood glucose was maintained at a higher level in comparison with the control group (P 0.05), but in the diabetic group, the fasting blood glucose level was stil higher and the body mass continued to decrease. These findings indicate that the transplantation of umbilical cord mesenchymal stem cels can be effective in the treatment of diabetes melitus in rats.
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BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into neuron-like cells directional y. Accordingly, BMSCs can be used as seed cells theoretical y in constructing tissue-engineered peripheral nerves. OBJECTIVE:Using combination of two cytokines to induce BMSCs differentiating into neuron-like cells directional y, and further to discusse its application in peripheral nerve injury. METHODS:BMSCs were isolated and purificated from the bone marrow of Wistar rats by using the differential adherence method. Basic fibroblast growth factor and epidermal growth factor were used to induce the BMSCs differentiating into neuron-like cells. The morphological change was observed and the neuronal specific markers were detected by immunohistochemistry technique. The morphological and immunohistological changes were also studied after the induce agent were removed. RESULTS AND CONCLUSION:With presence of morphological and immunohistochemical features of nerve cells induced by neurotrophic factors, BMSCs exhibited two or more processes that were interconnected as a meshwork;cellnucleus and nucleus could be observed with strong light refraction of cytoplasm. After immunohistochemical staining, neuroln specific enolase, neurofilament protein and synaptophysin protein positive cells were detected. A great amount of cells reversed to their original fibroblast-like morphology, and the expression of the three above-mentioned proteins decreased as the induce agent withdrawn. Our study showed that BMSCs can be induced to differentiate into neuron-like cells, but the transdifferentiation is a short-time reversible phenomenon.
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BACKGROUND:Whether adipose-derived mesenchymal stem cells are able to exert immunomodulatory effects in the treatment of myocardial infarction, as wel as the best time, is less reported. OBJECTIVE:To observe the effect of adipose-derived mesenchymal stem cells on inflammatory reaction and ventricular remodeling after myocardial infarction, and to explore the possible mechanisms of adipose-derived mesenchymal stem cells for the treatment of myocardial infarction. METHODS:Enzyme digestion method was employed to isolate and culture rat adipose-derived mesenchymal stem cells. By ligation of the left anterior descending coronary artery, we established animal models of myocardial infarction in 40 rats. The rats were randomly divided into four groups:sham group, control group (injected high-glucose Dulbecco’s modified Eagle’s medium), 3-hour transplantation group (transplanted adipose-derived mesenchymal stem cells after 3 hours of myocardial infarction), 7-day transplantation group (transplanted adipose-derived mesenchymal stem cells after 7 days of myocardial infarction). After 14 days of operation, the levels of tumor necrosis factor-αand interleukin-10 in the plasma were detected by enzyme linked immunosorbent assay. After 28 days of operation, the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening were measured by echocardiography. RESULTS AND CONCLUSION:Compared with the control group, in the 3-hour transplantation group and 7-day transplantation group, the levels of tumor necrosis factor-αwere significantly lower (P<0.01), and the levels of interleukin-10 were significantly higher (P<0.01) at postoperative 14 days;the left ventricular end diastolic diameter and left ventricular end systolic diameter in the two transplantation groups were also significantly smal er (P<0.05), but left ventricular ejection fraction and left ventricular fractional shortening were significantly elevated (P<0.05), which was more apparent in the 3-hour transplantation group than the 7-day transplantation group. Adipose-derived mesenchymal stem cells transplantation in acute phase of myocardial infarction can suppress the inflammatory response, regulate the cytokine network equilibrium, and thus delay ventricular remodeling and improve cardiac function.
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BACKGROUND:Currently, neural stem celltransplantation can be performed through three main approaches:local lesions, blood circulation, and cerebrospinal fluid. OBJECTIVE:To review the transplantation of neural stem cells or neural precursor cells via the cerebrospinal fluid in the treatment of central nervous system diseases. METHODS:A computer-based search of PubMed and CHKD databases was performed to retrieve articles concerning transplantation of neural stem cells via the cerebrospinal fluid, and its application and therapeutic mechanism in the treatment of central nervous system diseases in both animal experiment and clinic study published from 2000 to 2009. RESULTS AND CONCLUSION:It is suitable for neural stem cellsurvival, proliferation, and differentiation in the cerebrospinal fluid. Transplantation of neural stem cells via the cerebrospinal fluid is effective and feasible to treat central nervous system diseases. However, some problems have not been solved, such as the source of neural stem cells, the optimal time window and celldose, the safety and the long-term effect. Further studies are needed to pave the way for the intrathecal injection of neural stem cells in the treatment of central nervous system diseases.
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BACKGROUND:Bone marrow mesenchymal stem cell(BMSC) transplantation is one of the developmental directions in the treatment of femoral head necrosis. In recent years, the use of superparamagnetic iron oxide (SPIO) nanoparticles labeled target cells traced by MRI imaging method has become the focus of the study. OBJECTIVE:To observe the in vivo MRI tracking and the curative effects of SPIO-labeled BMSC transplantation on rabbit femoral head necrosis. METHODS:SPIO-labeled BMSCs, unlabeled BMSCs, and normal saline were injected in situ into the necrotic femoral head of rabbits. Fol owing MRI dectection, the image changes of transplanted BMSCs marked by SPIO were observed among the three scanning sequences of SE T2WI, FSE T2WI and GRE T2*WI. Meanwhile, the area percentage of newly formed bone trabecula in the defect samples under high power lens were observed and calculated for statistical analysis. RESULTS AND CONCLUSION:In situ celltransplantation group showed the emerging and extinctive time of the decreased-signal region was different among the three scanning sequences of SE T2WI, FSE T2WI and GRE T2*WI. It was found that the decreased-signal region of the MRI scanning sequences was the target of the present experiment. No obvious signal change occurred in the control side. After 6 weeks of transplantation, the area percentage of newly formed bone trabecula in the defect samples showed no difference in SPIO-labeled and unlabeled BMSC transplantation groups (P>0.05), but it was higher than that in the control side (P<0.01). The SPIO-labeled BMSCs and unlabeled BMSCs are shown to have the same effects in the treatment of femoral head necrosis. The SPIO-labeled BMSCs can be observed obviously by MRI detection in vitro.
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BACKGROUND:Bone marrow mesenchymal stem cells transplantation can change the surrounding microenvironment through paracrine mechanisms, and can be employed for treatment of serious damage to lung function through the promotion of angiogenesis, inhibition of apoptosis and maintaining functional stability of autonomic nervous system. OBJECTIVE:To observe the inflammatory reaction in experimental emphysema and inhibition of apoptosis through bone marrow mesenchymal stem cells transplantation. METHODS:Twenty-four Wistar female rats were randomly divided into three groups:healthy control group, model group and experimental group. In the latter two groups, smoking and endotracheal instil ation of porcine pancreatic elastase were performed to establish emphysema models. After modeling, bone marrow mesenchymal stem cells were injected via tail vein in the experimental group. Pathological changes of the lung, the level of tumor necrosis factor-alpha and cellnumber in the bronchoalveolar lavage fluid as wel as apoptotic index in lveolar wal s were detected after celltransplantation. RESULTS AND CONCLUSION:In the model and experimental groups, pathological changes of lung tissues were observed to different extent. The lung pathological changes were slighter in the experimental group than the model group (P<0.01). The level of tumor necrosis factor-alpha and apoptotic index in lung tissue were lower in the experimental group than the model group (P<0.01). These findings indicate that bone marrow mesenchymal stem cells can improve emphysema pathological y through inhibition of inflammatory response and apoptosis in experimental emphysema.
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BACKGROUND:In recent years, studies have shown that mesenchymal stem cells can secrete various growth factors, and has certain application prospect in the treatment of liver fibrosis. OBJECTIVE:To explore the different sources of mesenchymal stem cells in the treatment of liver fibrosis in rats. METHODS:Fifty Sprague-Dawley rats were given intraperitoneal injection of carbon tetrachloride to construct the model of liver fibrosis. Another 10 normal Sprague-Dawley rats were used as normal controls. Model rats were randomly divided into five groups, 10 rats in each group, including model control group, normal saline group, bone marrow mesenchymal stem cellgroup, umbilical cord mesenchymal stem cellgroup, and umbilical cord blood mesenchymal stem cellgroup. After 8 weeks of modeling, different sources of mesenchymal stem cells at a density of 2×106 were injected via tail vein into model rats. After 12 weeks, the rats were kil ed, and serum alanine aminotransferase, aspartate aminotransferase and albumin levels were detected as wel as the expression of type I col agen and glial fibril ary acidic protein in liver tissue was detected by fluorescence quantitative PCR method. RESULTS AND CONCLUSION:We have successful y established the SD rat model of hepatic fibrosis. Bone marrow mesenchymal stem cells aggravated hepatic fibrosis, umbilical cord blood and umbilical cord mesenchymal stem cells could reduce the level of hepatic fibrosis in rats. Umbilical cord mesenchymal stem cells had the most obvious effect that significantly reduced expressions of alanine aminotransferase, aspartate aminotransferase and type I col agen and glial fibril ary acidic protein. The results showed different sources of mesenchymal stem cells have different effects on rat fibrosis. Bone marrow mesenchymal stem cells aggravate hepatic fibrosis, and umbilical cord and umbilical cord blood stem cells can al eviate hepatic fibrosis in rats.
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BACKGROUND:Animal experiments have repeatedly verified that umbilical cord stem celltransplantation can improve the rotational behavior of rats with Parkinson’s disease, with lower immune rejection response. OBJECTIVE:To evaluate the therapeutic effects of human umbilical cord mesenchymal stem celltransplantation in the treatment of Parkinson’s disease using the Unified Parkinson’s Disease Rating Scale. METHODS:Fifteen patients with Parkinson’s disease were enrol ed, including 8 males and 7 females, aged 52-76 years. Hoehn&Yahr staging was 3-5. After informed consent was obtained from puerperae and the procedure was approved by the hospital ethics committee, ful-term maternal umbilical cord was aseptical y col ected, to culture umbilical cord mesenchymal stem cells. Al patients were hospitalized, and treated with human umbilical cord mesenchymal stem celltransplantation via carotid artery puncture. Neurological function of patients was assessed using a comprehensive rating scale for Parkinson’s disease before and 1 month after cells transplantation. Higher score indicated more severe neurological deficits. RESULTS AND CONCLUSION:Fifteen patients entered the result analysis. Compared with before transplantation, 15 patients showed significantly lowered scores on the Unified Parkinson’s Disease Rating Scale at 1 month after transplantation (P<0.05). The improvement was mainly concentrated in the tremor and rigidity, but bradykinesia and unstable position were not improved. Graft versus host disease did not occur in al 15 cases. These findings indicate that umbilical cord blood mesenchymal stem celltransplantation for treating Parkinson’s disease has obvious curative effects and significantly improves neurological functions.
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BACKGROUND:Epimedium has been used in the treatment of osteoporosis and repair of bone defects. OBJECTIVE:To explore the effects of epimedium on the osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS:A database search was performed to retrieve literatures addressing epimedium effects on the osteogenic differentiation of bone marrow mesenchymal stem cells. Then, the papers meeting the criteria were selected for in-depth analysis. During the osteogenic differentiation induced by epimedium, alkaline phosphatase, osteocalcin, osteopontin, transforming growth factorβ, bone morphogenetic proteins, osteocalcin, bone sialoprotein were detected in the bone marrow mesenchymal stem cells to understand the underlying mechanism of epimedium in proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION:Epimedium effects on bone marrow mesenchymal stem cells are shown in a dose-dependent manner. During the early induction, icari n can increase cellphosphatase activity;in the late induction, icari n can increase calcified nodules, promote osteocalcin secretion, significantly improve the expressions of transforming growth factorβ1, bone morphogenetic protein 2, insulin-like growth factor-1, osteopontin and bone sialoprotein. Epimedium, which can be used as an excellent osteoinductive factor, improves the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.
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BACKGROUND:Mesenchymal stem cells are found to have the immunoregulatory activities and a potential application prospect in the treatment of autoimmune diseases. OBJECTIVE:To explore the mechanism of transplanting mesenchymal stems cells on the treatment of multiple sclerosis. METHODS:The mouse mesenchymal stems cells were prepared, and injected into the al ogenic and syngenic normal mice, to detect the frequency of CD4+CD25+Foxp3+T cells in the spleen, thymus, and lymph nodes by flow cytometry, and to detect the Foxp3, transforming growth factor-β1, and interleukin-10 mRNA in the spleen, thymus, and lymph nodes by reverse transcription-PCR. RESULTS AND CONCLUSION:Transplantation of mesenchymal stem cells on normal mice led to a significant up-regulation of CD4+CD25+Foxp3+T cells, Foxp3, transforming growth factor-β1, and interleukin-10 mRNA in the spleen, thymus, and lymph nodes both in the al ogenic and syngenic transplant groups. Transplantation of mesenchymal stem cells may be an available method in the treatment of autoimmune diseases, and CD4+CD25+Foxp3+T cell, Foxp3, transforming growth factor-β1, and interleukin-10 may be involved in this process.
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BACKGROUND:Myocardial infarction patients commonly appear to have left ventricular remodeling and heart failure. Because of physical characteristics, these two complications are more likely to occur in elderly patients with myocardial infarction. In recent years, stem celltransplantation in the treatment of acute myocardial infarction and heart failure has become a hot topic, and the feasibility and safety has been confirmed, but its long-term outcomes in elderly patients are stil unclear. OBJECTIVE:To assess the long-term effect of transplantation of autologous peripheral blood stem cells on the left ventricular remodeling and heart function in the old patients with myocardial infarction. METHODS:Thirty old patients (age ≥ 60 years) with myocardial infarction were randomly assigned to receive intracoronary transplantation of peripheral blood stem cells fol owing bone marrow cells mobilization by granulocyte colony-stimulating factor ( 300-600μg per day) subcutaneously for 5 days in addition to conventional therapy (standard drug therapy and percutaneous coronary intervention;transplantation group, n=15) or standard therapy (standard drug therapy and percutaneous coronary intervention;control group, n=15) . Complications during intervention, left ventricular function and left ventricular remodeling at baseline and 6, 12, 24, 60 months after treatment were monitored. RESULTS AND CONCLUSION:Left ventricular function, left ventricular end diastolic volume, and left ventricular end-systolic volume were significantly improved 6,12, 24, 60 months after autologous peripheral blood stem celltransplantation compared to baseline, while these parameters remained unchanged in the control group. These parameters had statistical difference between the two groups after treatment. During the fol ow-up, no severe side effects were observed. These findings indicate that autologous peripheral blood stem celltransplantation leads to significant and longstanding improvements in left ventricular performance of old patients with myocardial infarction, and shows good safety.
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BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy. OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy. METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis. RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.
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BACKGROUND:Several studies have demonstrated embryonic stem cells induced neural precursor cells can promote functional recovery in rats with spinal cord injury. OBJECTIVE:To study the effect of in vitro cultured embryonic stem cells induced neural precursor cells in rats with spinal cord injury. METHODS:Total y 144 rats were randomly divided into three groups. Experiment group and control group rats had spinal cord transection injury. Embryonic stem cells-derived cells were injected into the vertebral canal at rostral and caudal segment perilesional y for the experiment group whereas PBS solution was injected instead of cells in the control group. Sham surgery group rats had only laminectomy without any spinal cord injury and treatment. RESULTS AND CONCLUSION:The experimental result showed that at day 21 post-injury, the regional expression of transforming growth factor-β1 was greater in rats from the control group in comparison to the experiment group (P<0.05). At each time point after spinal cord injury in rats, the expression of myelin basic protein in the spinal cord was significantly higher in the experiment group than the control group (P<0.05). After celltransplantation, Basso, Beattie, and Bresnahan scores of the experiment group at different time points were significantly higher than those of the control group (P<0.05). Transplantation of in vitro cultured embryonic stem cells induced neural precursor cells can reduce the late expression of transforming growth factor-β1, and can increase the expression of myelin basic protein which contributes to the recovery of rats with completely transected spinal cord injury.
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BACKGROUND:Autologous stem celltransplantation to the heart is a research direction of heart failure treatment, but there are relatively few of studies about autologous bone marrow mesenchymal stem celltransplantation targeting the cardiac conduction system. OBJECTIVE:To evaluate the potential of rabbit bone marrow mesenchymal stem cells for treatment of heart block. METHODS:Rabbit bone marrow mesenchymal stem cells were induced by 5-azacytidine to differentiate into cardiomyocyte-like cells. After thoracotomy, the left atrium-left ventricular anterior wal was sutured in 14 New Zealand white rabbits (8 in the experimental group and 6 in the control group). One month after the surgery, in the experimental group, autologous bone marrow mesenchymal stem cells induced by 5-azacytidine for 4 weeks were labeled with 4',6-diamidino-2-phenylindole and then injected into the suture area when opening the thoracic again. In the control group, cells cultured in medium were used. One month after celltransplantation, the third thoracotomy was done to insert electrodes into the left atrium and left ventricular anterior wal , for cardiac electrophysiological detection. Whether atrioventricular pathway formed in the suture area was observed. RESULTS AND CONCLUSION:After cells were transplanted into the sutured area, two rabbits in the experimental group were discovered to form the atrioventricular pathway in the sutured area through cardiac electrophysiological examination. After transplantation, transplanted cells were visible on the heart frozen sections under fluorescence microscope in the left ventricle and sutured area, but there was no cellin the control group. In the experimental group, bone marrow mesenchymal stem cells expressed Cx43 and formed gap junction intercellular communication with cardiomyocytes, which was presented as formation of the atrioventricular pathway on cardiac electrophysiology examination. These findings indicate that bone marrow mesenchymal stem cells can be used to treat cardiac conduction system block diseases.
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BACKGROUND:So far, the short-term changes of various organs after injection of umbilical cord mesenchymal stem cells have been reported, but there are few studies on the long-term changes of various organs in healthy rats after repeated intramuscular injection of umbilical cord mesenchymal stem cells. OBJECTIVE:To observe the security of intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. METHODS:Sixty male SPF Wistar rats were divided into six groups randomly:normal group (suspension liquid of umbilical cord mesenchymal stem cells);control group with culture solution;supernatant group (supernatant of human umbilical cord mesenchymal stem cells);low concentration group (0.25×105 human umbilical cord mesenchymal stem cells);moderate concentration group (1.0×105 human umbilical cord mesenchymal stem cells);high concentration group (4.0×105 human umbilical cord mesenchymal stem cells). Each rat was injected 0.8 mL liquid in muscle, 0.2 mL in each limb, twice at weeks 1 and 4. Biochemical tests were conducted before and after injection. At the end of 8 weeks, al the rats were kil ed and hematoxylin-eosin staining was done with the liver, spleen, lung, kidney, brain and muscle. RESULTS AND CONCLUSION:There was no abnormal change about biochemical tests and hematoxylin-eosin staining after the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. No significant alteration was observed in the liver, spleen, lung, kidney, brain, and muscle of the limb after the injection of heterogeneous umbilical cord mesenchymal stem cells under suitable concentration. These findings indicate intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells at certain concentrations is safe and reliable.
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BACKGROUND:Recent studies have shown that the large-dose regular insulin therapy used to control blood glucose levels can cause 50%of patients suffering from vascular, optic nerve and kidney complications. Previous results from authors exhibit that when al ogeneic hematopoietic stem celltransplantation is applied for treatment of leukemia, diabetic symptoms in patients disappear. Dose it prompt that al ogeneic hematopoietic stem celltransplantation is an effective therapy for treatment of diabetes mel itus? OBJECTIVE:To explore the feasibility of hematopoietic stem celltransplantation for treatment of diabetes mel itus. METHODS:A retrospective analysis was done regarding the data of patients with hematological diseases complicated with diabetes mel itus who underwent al ogenetic hematopoietic stem celltransplantation. Four patients with acute lymphocyte leukemia, chronic myelogenous leukemia, aplastic anemia, and myolodysplastic syndromes, respectively, were complicated with diabetes mel itus. Conditioning regimen was cyclophosphamide+total body irradiation protocol. Cyclosporin A and short-term methotrexate were used for graft-versus-host disease prophylaxis. Blood glucose was control ed by oral hypoglycemic drugs or insulin injections before transplantation. RESULTS AND CONCLUSION:Al the four patients were successful y engrafted. Fasting glucose level of the four patients recovered at 4-6 months after hematopoietic stem celltransplantation (without hypoglycemic drugs). One patient died of leukemia relapse after 12 months of hematopoietic stem celltransplantation. The other three patients had disease-free survival until the time of fol ow-up.
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BACKGROUND:The CD4+CD25+FOXP3+Treg cells have immunosuppression effect, and it is speculated that these cells may restrain the occurrence of acute graft-versus-host disease. OBJECTIVE:To observe the variety of the CD4+CD25+FOXP3+Treg cells in the peripheral blood from donors before and after granulocyte colony stimulating factor mobilization, and study the relationship between CD4+CD25+FOXP3+Treg cells and acute graft-versus-host disease. METHODS:Ninety patients with malignant blood diseases who undertook al ogeneic hematopoietic stem celltransplantation and their donors were observed. Granulocyte colony stimulating factor 5μg/kg was injected subcutaneously into the donor per 12 hours for 5 days, and the stem cells were col ected before and after mobilization. The ratio of CD4+CD25+FOXP3+Treg cells in the peripheral blood was detected before and after mobilization with flow cytometry, and the ratio of these cells in the stem cellsuspension was measured by the same method. The patients were divided into two groups according to the CD4+CD25+FOXP3+Treg cells ratio:high dosage group (≥5%) and low dosage group (<5%). The incidence of acute graft-versus-host disease was observed in the two groups after transplantation. RESULTS AND CONCLUSION:The ratio of the CD4+CD25+FOXP3+Treg cells in the donor before and after mobilization were 11.3%and 1.5%,respectively, and there was a significant difference (P<0.05). The ratio of the CD4+CD25+FOXP3+Treg cells was 3.4%in the patients with acute graft-versus-host disease, and 15.7%in the patients with no acute graft-versus-host disease, showing a significant difference (P<0.05). After hematopoietic reconstitution, the incidence of acute graft-versus-host disease was 18.4%in the high dosage group and 48.1%in the low dosage group, and there was a significant difference between the two groups (P<0.05). Therefore, the granulocyte colony stimulating factor can lower the ratio of CD4+CD25+FOXP3+Treg cells in the human peripheral blood. The increase in CD4+CD25+FOXP3+Treg cells can restrain the occurrence of acute graft-versus-host disease.
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BACKGROUND:Spinocerebel ar ataxia is a inherited neurodegenerative disease with progressive cerebel ar masonic movement disorders as the main clinical manifestation. So far, no drug is available to control the disease progression. OBJECTIVE:To observe the clinical effect of umbilical cord mesenchymal stem cells in treating spinocerebel ar ataxia by intrathecal injection. METHODS:Thirty-eight cases of spinocerebel ar ataxia were given umbilical cord mesenchymal stem cells by intrathecal injection, 1×106/kg once a week, four times as a course. These 38 cases received 52 courses. Among them, 27 cases received 1 course, 8 cases received 2 courses and 3 cases received 3 courses. International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL) were used to evaluate patients’ neural functions (the greater scores, the more severe damage) and ability of daily living (the lower score, the stronger the ability of daily living). After treatment, al patients were subjected to fol ow-up visit. RESULTS AND CONCLUSION:The total effective rate of 52 courses of treatment was 84.62%. ICARS and ADL scores were significantly decreased at 1 month after treatment (P<0.01). In most of effective patients, unstable walking and standing, slow movement, upper limb fine motor disorder, writing difficulties, dysarthria, eye movement disorders were improved. After treatment, common adverse effects were dizziness (1 case), low back pain (2 cases), headache (1 case), and fever (2 cases). Al these symptoms disappeared within 1-3 days. No treatment-related adverse events happened in the median fol ow-up of 39 months (11-59 months). The il ness of effective patients had been stable for 1-19 months, average (5.95±4.84) months. Intrathecal injection of umbilical cord mesenchymal stem cells is safe to ameliorate clinical symptoms to some extent within a certain time. It may delay the progression of spinocerebel ar ataxia. Multiple courses of treatment can help to further improve neurological function in most patients.