This letter addresses the review titled“Wharton’s jelly mesenchymal stem cells:Future regenerative medicine for clinical applications in mitigation of radiation injury”.The review highlights the regenerative potent...This letter addresses the review titled“Wharton’s jelly mesenchymal stem cells:Future regenerative medicine for clinical applications in mitigation of radiation injury”.The review highlights the regenerative potential of Wharton’s jelly mesenchymal stem cells(WJ-MSCs)and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine.The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable,which will provide a new strategy for improving bone regeneration under diabetic conditions.展开更多
Objective To construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotropnic factor (GDNF), and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by...Objective To construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotropnic factor (GDNF), and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by transfecting it into bone marrow stromal cells (BMSCs). Methods pLenti6/V5-GDNF plasmid was set up by double restriction enzyme digestion and ligation, and then the plasmid was transformed into Top10 cells. Purified pLenti6/V5-GDNF plasmids from the positive clones and the packaging mixture were cotransfected to the 293FT packaging cell line by Lipofectamine2000 to produce lentivirus, then the concentrated virus was transduced to BMSCs. Overexpression of GDNF in BMSCs was tested by RT-PCR, ELISA and immunocytochemistry, and its neuroprotection for lactacystin-damaged PC12 cells was evaluated by MTT assay. Results Virus stock of GDNF was harvested with the titer of 5.6×10^5 TU/mL. After tmnsduction, GDNF-BMSCs successfully secreted GDNF to supematant with nigher concentration (800 pg/mL) than BMSCs did (less than 100 pg/mL). The supematant of GDNF-BMSCs could significantly alleviate the damage of PC12 cells induced by lactacystin (10 μmol/L). Conclusion Overexpression of lentivirus-mediated GDNF in the BMSCs cells can effectively protect PC12 cells from the injury by the proteasome inhibitor.展开更多
Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental factors.Up to 50%of IBD patients experience at least one extraint...Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental factors.Up to 50%of IBD patients experience at least one extraintestinal manifestation;among them is the involvement of bone density which is referred to as metabolic bone disease(MBD),including osteopenia and osteoporosis.Bone alterations in IBDs population appear to have a multifactorial etiology:Decreased physical activity,inflammation-related bone resorption,multiple intestinal resections,dietary malabsorption of minerals and vitamin D deficiency,genetic factors,gut-bone immune signaling interaction,steroid treatment,microbiota and pathogenic micro-organisms interaction,and dietary malabsorption of minerals,that,all together or individually,may contribute to the alteration of bone mineral density.This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility.We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.展开更多
In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer's disease, resulted in s...In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer's disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer's disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.展开更多
AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grow...AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.展开更多
The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow...The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option.展开更多
On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tri...On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. Adult autologous bone marrow mesenchymal stem cells isolated from patient’s own bone marrow and were cultured and placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently using ultrasound. Three months later, endometrium partly recovered with improved ultrasonic echo. This resulted in spontaneous pregnancy followed by confirmation of gestational sac, yolk sac, and primitive heart tube pulse on ultrasound. Autologous bone marrow derived mesenchymal stem cells could regenerate injured endometrium not responding to conventional treatment and can be used as an alternative in females with severe Asherman’s syndrome.展开更多
BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To r...BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell’s disease.METHODS Patients with Kümmell’s disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed.Patients meeting the inclusion and exclusion criteria were divided into two groups:Traditional single infusion and sequential infusion(SI).The visual analog scale(VAS)and Oswestry disability index(ODI)were evaluated and compared,and duration of operation,bone cement content and complications were recorded.RESULTS Forty-five patients were included in this study;there were 24 in the traditional single infusion group and 21 in the SI group.The VAS and ODI were significantly different for both groups when compared pre-and postoperatively,whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically.When the VAS and ODI of the two groups were compared,there were no significant differences at any time point.The leakage rate of bone cement was significantly lower in the SI group(14.3%,3 of 21)than that in the traditional single infusion group(41.7%,10 of 24).CONCLUSION SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell’s disease,and this technique could decrease the incidence of bone cement leakage.展开更多
AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were i...AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate cells.CONCLUSION: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.展开更多
AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unse...AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for thebone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.展开更多
BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multip...BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.展开更多
Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson's disease significantly improved behavior and increased striatal dopamine content. In the prese...Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson's disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson's disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson's disease.展开更多
A case of florid reactive periostitis ossificans(RPO) arising in a long bone is presented. This is a rare bone proliferation with a pronounced periosteal reaction. Less than 100 cases have been described in the litera...A case of florid reactive periostitis ossificans(RPO) arising in a long bone is presented. This is a rare bone proliferation with a pronounced periosteal reaction. Less than 100 cases have been described in the literature with far fewer outside the bones of the hand, feet, fingers, and toes. Although the etiology is unknown, a relationship to preceding trauma is suggested. The imaging and histologic features show an overlap with other bone lesions including bizarre parosteal osteochondromatous proliferation, subungual exostosis, and malignant surface tumors of bone and cartilage which include, periosteal and parosteal osteosarcoma. It is important to recognize the clinical presentation and diagnostic features of RPO as a benign entity so that it is not mistaken for a more aggressive neoplasm. We present a case of a right distal humeral lesion that on histopathological review revealed florid RPO. This diagnosis was not suspected on imaging studies, but was made on open biopsy of the mass. The patient remains disease free, years postoperatively. In addition to presenting this unique case report, we review the pertinent literature, and offer a differential diagnosis and treatment strategy for its management.展开更多
BACKGROUND Little is known about inflammatory bowel disease(IBD)burden and its impact on bone mineral density(BMD)among adult patients in Saudi Arabia.To the best of our knowledge,our study is the only study to give a...BACKGROUND Little is known about inflammatory bowel disease(IBD)burden and its impact on bone mineral density(BMD)among adult patients in Saudi Arabia.To the best of our knowledge,our study is the only study to give an update about this health problem in adult Saudi patients with IBD.IBD is a great risk factor for reduced BMD due to its associated chronic inflammation,malabsorption,weight loss and medication side effects.Consequently,screening for reduced BMD among patients with IBD is of utmost importance to curb and control anticipated morbidity and mortality among those patients.AIM To assess the relationship between IBD and BMD in a sample of adult Saudi patients with IBD.METHODS Ninety adult patients with IBD-62 Crohn’s disease(CD)and 28 ulcerative colitis(UC)-were recruited from King Fahad Specialist Hospital gastroenterology clinics in Buraidah,Al-Qassim.All enrolled patients were interviewed for their demographic information and for IBD-and BMD-related clinical data.All patients had the necessary laboratory markers and dual-energy x-ray absorptiometry scans to evaluate their BMD status.Patients were divided into two groups(CD and UC)to explore their clinical characteristics and possible risk factors for reduced BMD.RESULTS The CD group was significantly more prone to osteopenia and osteoporosis compared to the UC group;44%of the CD patients had normal BMD,19%had osteopenia,and 37%had osteoporosis,while 78%of the UC patients had normal BMD,7%had osteopenia,and 25%had osteoporosis(P value<0.05).In the CD group,the lowest t-score showed a statistically significant correlation with body mass index(BMI)(r=0.45,P<0.001),lumbar z-score(r=0.77,P<0.05)and femur z-score(r=0.85,P<0.05).In the UC group,the lowest t-score showed only statistically significant correlation with the lumbar z-score(r=0.82,P<0.05)and femur z-score(r=0.80,P<0.05).The ROC-curve showed that low BMI could predict the lowest t-score in the CD group with the best cut-off value at≤23.43(m/kg2);area under the curve was 0.73(95%CI:0.59–0.84),with a sensitivity of 77%,and a specificity of 63%.CONCLUSION Saudi patients with IBD still have an increased risk of reduced BMD,more in CD patients.Low BMI is a significant risk factor for reduced BMD in CD patients.展开更多
How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated i...How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. The GNAS gene encodes Gαs that transduces GPCR signaling. GNAS activation or loss-of-function mutations in humans cause fibrous dysplasia(FD) or progressive osseous heteroplasia(POH) that shows craniofacial hyperostosis or craniosynostosis, respectively. We find here that, while Hh ligand-dependent Hh signaling is essential for endochondral ossification, it is dispensable for intramembranous ossification, where Gαsregulates Hh signaling in a ligand-independent manner. We further show that Gαscontrols intramembranous ossification by regulating both Hh and Wnt/β-catenin signaling. In addition, Gαsactivation in the developing cranial bone leads to reduced ossification but increased cartilage presence due to reduced cartilage dissolution, not cell fate switch. Small molecule inhibitors of Hh and Wnt signaling can effectively ameliorate cranial bone phenotypes in mice caused by loss or gain of Gnas function mutations, respectively. Our work shows that studies of genetic diseases provide invaluable insights in both pathological bone defects and normal bone development, understanding both leads to better diagnosis and therapeutic treatment of bone diseases.展开更多
BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone ...BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone cement implantation.CASE SUMMARY An 80-year-old patient with pemphigus and Parkinson’s disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation.The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline(2μg/mL)at a rate of 30 mL/h.Subsequently,the symptoms of BCIS were markedly alleviated,and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later.The patient was then transferred to the Department of Orthopedics,and anticoagulation therapy began at 12 h postoperatively.No other complications were observed.CONCLUSION This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson’s disease.展开更多
A rat model of Parkinson's disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and wer...A rat model of Parkinson's disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein (GFAP), nestin and neuron-specific enolase (NSE). Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson's disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.展开更多
AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was pe...AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was performed. Four studies with a total of 54 TKAs were included for analysis. Functional outcomes, pain scores, complications and revision rates were assessed. The mean age was 72.0 years and the mean follow-up was 7.5 years.RESULTS All studies reported significant improvement in knee function and pain scores following TKA. There were 2 cases of aseptic loosening, with one patient requiring revision of the femoral component 10 years after the index procedure. Malalignment, bone loss, soft tissue contractures were the most commonly reported intraoperative challenges. There were five cases(9%) that were complicated by intra-operative patellar tendon avulsion.CONCLUSION The findings support the use of TKA in patients with PDB. The post-operative functional outcomes are largely similar to other patients, however there are specific perioperative challenges that have been highlighted, in particular the high risk for patellar tendon avulsion.展开更多
BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural...BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.展开更多
基金China Postdoctoral Science Foundation,No.2024M751344the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088.
文摘This letter addresses the review titled“Wharton’s jelly mesenchymal stem cells:Future regenerative medicine for clinical applications in mitigation of radiation injury”.The review highlights the regenerative potential of Wharton’s jelly mesenchymal stem cells(WJ-MSCs)and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine.The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable,which will provide a new strategy for improving bone regeneration under diabetic conditions.
基金This work was supported by the Natural Science Foundation of Shanghai Municipality(No.03ZR14016).
文摘Objective To construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotropnic factor (GDNF), and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by transfecting it into bone marrow stromal cells (BMSCs). Methods pLenti6/V5-GDNF plasmid was set up by double restriction enzyme digestion and ligation, and then the plasmid was transformed into Top10 cells. Purified pLenti6/V5-GDNF plasmids from the positive clones and the packaging mixture were cotransfected to the 293FT packaging cell line by Lipofectamine2000 to produce lentivirus, then the concentrated virus was transduced to BMSCs. Overexpression of GDNF in BMSCs was tested by RT-PCR, ELISA and immunocytochemistry, and its neuroprotection for lactacystin-damaged PC12 cells was evaluated by MTT assay. Results Virus stock of GDNF was harvested with the titer of 5.6×10^5 TU/mL. After tmnsduction, GDNF-BMSCs successfully secreted GDNF to supematant with nigher concentration (800 pg/mL) than BMSCs did (less than 100 pg/mL). The supematant of GDNF-BMSCs could significantly alleviate the damage of PC12 cells induced by lactacystin (10 μmol/L). Conclusion Overexpression of lentivirus-mediated GDNF in the BMSCs cells can effectively protect PC12 cells from the injury by the proteasome inhibitor.
文摘Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental factors.Up to 50%of IBD patients experience at least one extraintestinal manifestation;among them is the involvement of bone density which is referred to as metabolic bone disease(MBD),including osteopenia and osteoporosis.Bone alterations in IBDs population appear to have a multifactorial etiology:Decreased physical activity,inflammation-related bone resorption,multiple intestinal resections,dietary malabsorption of minerals and vitamin D deficiency,genetic factors,gut-bone immune signaling interaction,steroid treatment,microbiota and pathogenic micro-organisms interaction,and dietary malabsorption of minerals,that,all together or individually,may contribute to the alteration of bone mineral density.This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility.We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.
基金sponsored by Science and Technology Support for Major Projects of Hebei Province, No. 09276103DHebei Province Science and Technology Research and Development Program, No. 08206120D
文摘In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer's disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer's disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.
文摘AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
文摘The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option.
文摘On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. Adult autologous bone marrow mesenchymal stem cells isolated from patient’s own bone marrow and were cultured and placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently using ultrasound. Three months later, endometrium partly recovered with improved ultrasonic echo. This resulted in spontaneous pregnancy followed by confirmation of gestational sac, yolk sac, and primitive heart tube pulse on ultrasound. Autologous bone marrow derived mesenchymal stem cells could regenerate injured endometrium not responding to conventional treatment and can be used as an alternative in females with severe Asherman’s syndrome.
文摘BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell’s disease.METHODS Patients with Kümmell’s disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed.Patients meeting the inclusion and exclusion criteria were divided into two groups:Traditional single infusion and sequential infusion(SI).The visual analog scale(VAS)and Oswestry disability index(ODI)were evaluated and compared,and duration of operation,bone cement content and complications were recorded.RESULTS Forty-five patients were included in this study;there were 24 in the traditional single infusion group and 21 in the SI group.The VAS and ODI were significantly different for both groups when compared pre-and postoperatively,whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically.When the VAS and ODI of the two groups were compared,there were no significant differences at any time point.The leakage rate of bone cement was significantly lower in the SI group(14.3%,3 of 21)than that in the traditional single infusion group(41.7%,10 of 24).CONCLUSION SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell’s disease,and this technique could decrease the incidence of bone cement leakage.
文摘AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate cells.CONCLUSION: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.
基金Supported by the Dunhill Trust, National Osteoporosis Society and National Association of Colitis and Crohn's disease
文摘AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for thebone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.
基金Supported by Special Scientific Research Project of Military Healthcare,No.19BJZ29Beijing Haidian District Health Development Research and Cultivation Program,No.HP-2021-03-80303.
文摘BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.
基金supported by grants from the Ministryof Health of China, No. 2011010009the Science and Technology Department of Henan Province, No.112102310230
文摘Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson's disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson's disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson's disease.
基金Supported by The University of Alabama at Birmingham,Alabama and The Orthopaedic Center,Birmingham,AL,United States
文摘A case of florid reactive periostitis ossificans(RPO) arising in a long bone is presented. This is a rare bone proliferation with a pronounced periosteal reaction. Less than 100 cases have been described in the literature with far fewer outside the bones of the hand, feet, fingers, and toes. Although the etiology is unknown, a relationship to preceding trauma is suggested. The imaging and histologic features show an overlap with other bone lesions including bizarre parosteal osteochondromatous proliferation, subungual exostosis, and malignant surface tumors of bone and cartilage which include, periosteal and parosteal osteosarcoma. It is important to recognize the clinical presentation and diagnostic features of RPO as a benign entity so that it is not mistaken for a more aggressive neoplasm. We present a case of a right distal humeral lesion that on histopathological review revealed florid RPO. This diagnosis was not suspected on imaging studies, but was made on open biopsy of the mass. The patient remains disease free, years postoperatively. In addition to presenting this unique case report, we review the pertinent literature, and offer a differential diagnosis and treatment strategy for its management.
基金Sulaiman Al Rajhi University,Saudi Arabia,from the Annual Budget of their Research Unit.
文摘BACKGROUND Little is known about inflammatory bowel disease(IBD)burden and its impact on bone mineral density(BMD)among adult patients in Saudi Arabia.To the best of our knowledge,our study is the only study to give an update about this health problem in adult Saudi patients with IBD.IBD is a great risk factor for reduced BMD due to its associated chronic inflammation,malabsorption,weight loss and medication side effects.Consequently,screening for reduced BMD among patients with IBD is of utmost importance to curb and control anticipated morbidity and mortality among those patients.AIM To assess the relationship between IBD and BMD in a sample of adult Saudi patients with IBD.METHODS Ninety adult patients with IBD-62 Crohn’s disease(CD)and 28 ulcerative colitis(UC)-were recruited from King Fahad Specialist Hospital gastroenterology clinics in Buraidah,Al-Qassim.All enrolled patients were interviewed for their demographic information and for IBD-and BMD-related clinical data.All patients had the necessary laboratory markers and dual-energy x-ray absorptiometry scans to evaluate their BMD status.Patients were divided into two groups(CD and UC)to explore their clinical characteristics and possible risk factors for reduced BMD.RESULTS The CD group was significantly more prone to osteopenia and osteoporosis compared to the UC group;44%of the CD patients had normal BMD,19%had osteopenia,and 37%had osteoporosis,while 78%of the UC patients had normal BMD,7%had osteopenia,and 25%had osteoporosis(P value<0.05).In the CD group,the lowest t-score showed a statistically significant correlation with body mass index(BMI)(r=0.45,P<0.001),lumbar z-score(r=0.77,P<0.05)and femur z-score(r=0.85,P<0.05).In the UC group,the lowest t-score showed only statistically significant correlation with the lumbar z-score(r=0.82,P<0.05)and femur z-score(r=0.80,P<0.05).The ROC-curve showed that low BMI could predict the lowest t-score in the CD group with the best cut-off value at≤23.43(m/kg2);area under the curve was 0.73(95%CI:0.59–0.84),with a sensitivity of 77%,and a specificity of 63%.CONCLUSION Saudi patients with IBD still have an increased risk of reduced BMD,more in CD patients.Low BMI is a significant risk factor for reduced BMD in CD patients.
基金supported by the NIH grants R01DE025866 from NIDCRR01AR070877 from NIAMSsupported by the 111 Project, MOE (B14038), China
文摘How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. The GNAS gene encodes Gαs that transduces GPCR signaling. GNAS activation or loss-of-function mutations in humans cause fibrous dysplasia(FD) or progressive osseous heteroplasia(POH) that shows craniofacial hyperostosis or craniosynostosis, respectively. We find here that, while Hh ligand-dependent Hh signaling is essential for endochondral ossification, it is dispensable for intramembranous ossification, where Gαsregulates Hh signaling in a ligand-independent manner. We further show that Gαscontrols intramembranous ossification by regulating both Hh and Wnt/β-catenin signaling. In addition, Gαsactivation in the developing cranial bone leads to reduced ossification but increased cartilage presence due to reduced cartilage dissolution, not cell fate switch. Small molecule inhibitors of Hh and Wnt signaling can effectively ameliorate cranial bone phenotypes in mice caused by loss or gain of Gnas function mutations, respectively. Our work shows that studies of genetic diseases provide invaluable insights in both pathological bone defects and normal bone development, understanding both leads to better diagnosis and therapeutic treatment of bone diseases.
文摘BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone cement implantation.CASE SUMMARY An 80-year-old patient with pemphigus and Parkinson’s disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation.The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline(2μg/mL)at a rate of 30 mL/h.Subsequently,the symptoms of BCIS were markedly alleviated,and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later.The patient was then transferred to the Department of Orthopedics,and anticoagulation therapy began at 12 h postoperatively.No other complications were observed.CONCLUSION This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson’s disease.
文摘A rat model of Parkinson's disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein (GFAP), nestin and neuron-specific enolase (NSE). Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson's disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.
文摘AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was performed. Four studies with a total of 54 TKAs were included for analysis. Functional outcomes, pain scores, complications and revision rates were assessed. The mean age was 72.0 years and the mean follow-up was 7.5 years.RESULTS All studies reported significant improvement in knee function and pain scores following TKA. There were 2 cases of aseptic loosening, with one patient requiring revision of the femoral component 10 years after the index procedure. Malalignment, bone loss, soft tissue contractures were the most commonly reported intraoperative challenges. There were five cases(9%) that were complicated by intra-operative patellar tendon avulsion.CONCLUSION The findings support the use of TKA in patients with PDB. The post-operative functional outcomes are largely similar to other patients, however there are specific perioperative challenges that have been highlighted, in particular the high risk for patellar tendon avulsion.
基金the National High-Tech Research & Development Program of China, No. 2006AA02A128the National Natural Science Foundation of China, No. 30670667
文摘BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.