Injectable tissue-engineered bone using autogenous bone marrow-derived stromal cells for maxillary sinus augmentation: clinical application report from a 2-6-year follow-up

This clinical study used injectable tissue-engineered bone, along with bone marrow-derived stromal cells (BMDSCs) and platelet-rich plasma (PRP), to conduct maxillary sinus floor augmentation by the simultaneous placement of bone graft and dental implants and to examine the state of regenerated bone after functional loading in 16 sinus augmentations in 12 patients whose alveolar crestal bone height was 2-10 mm. We used PRP as an autologous scaffold-which provides signal molecules-with in vitro expanded BMDSCs to enhance osteogenesis. All 41 dental implants prepared with the materials were clinically stable after second-stage surgery. The height of mineralized tissue at 2 years showed the mean increases of 8.8 +/- 1.6 mm compared to preoperative values, and no adverse effects and remarkable bone absorption were seen in the 2-6-year follow-up time. Although these results are preliminary, injectable tissue-engineered bone would stably predict the success of bone formation and dental implants, reduce patient burden, and provide minimally invasive cell therapy for patients.     

数字三维影像测量模型在复杂长骨骨折修复中的应用：随机对照、6个月随访、临床试验方案

BACKGROUND: During internal fixation for complex long bone fractures, it is difficult to position the internal fixator completely to the contours of the bone surface, often resulting in unstable fixation and affecting the quality of the repair. Digital three-dimensional (3D) models were therefore established based on computed tomography (CT) scans that closely reflected the site and degree of fractures, thereby guiding precise positioning of the internal fixator. From a safety point of view, the digital 3D-derived model was created to ensure that the internal fixator could achieve better repairs of complex long bone fractures.     

Electrophysiological indices associated with social functioning outcome in schizophrenia: a 5-year follow-up study

We previously demonstrated that event-related potentials (ERPs), such as N1/N2b amplitudes in an auditory selective attention task, were significantly associated with communication skills of schizophrenia. The present study investigated the relationship between N1/N2b amplitudes and the quality of life (QOL) 5 years after ERP measurement. QOL of 15 patients with schizophrenia was assessed using the quality of life scale (QLS). Correlational analyses revealed a significant relationship between N2b, but not N1, amplitude and specific domains of QOL. N2b amplitude, an electrophysiological index of orienting response, may be associated with longitudinal social functioning outcome in schizophrenia.     

Stem cells in the mammalian eye: a tool for retinal repair

Degenerative diseases and traumatic injuries of the central nervous system (CNS) are major causes of long-term disability, whether such insults impact the brain, retina, or spinal cord. Substantial tissue destruction can be sustained by these complex structures without loss of life, while the lack of effective CNS regeneration frequently results in a marked degradation in quality of life. Only recently has it become clear that an enormous potential for regeneration is present within the mammalian CNS. The challenge now presented to researchers is to harness this potential to treat disease. Recent studies showing that stem and progenitor cells can be isolated from the mammalian retina have prompted many researchers to develop strategies aimed at restoring function to the diseased retina. This review summarizes a number of issues related to this goal, including retinal development, transplantation immunology, tissue engineering, and large animal studies. The application of these divergent disciplines to stem cell technology is vital to the development of the novel strategies needed to make retinal transplantation a clinical success.     

Xenopus laevis as a novel model to study long bone critical-size defect repair by growth factor-mediated regeneration

We used the tarsus of an adult Xenopus laevis frog as an in vivo load-bearing model to study the regeneration of critical-size defects (CSD) in long bones. We found the CSD for this bone to be about 35% of the tarsus length. To promote regeneration, we implanted biocompatible 1,6 hexanediol diacrylate scaffolds soaked with bone morphogenetic proteins-4 and vascular endothelial growth factors. In contrast to studies that use scaffolds as templates for bone formation, we used scaffolds as a growth factor delivery vehicle to promote cartilage-to-bone regeneration. Defects in control frogs were filled with scaffolds lacking growth factors. The limbs were harvested at a series of time points ranging from 3 weeks to 6 months after implantation and evaluated using micro-computed tomography and histology. In frogs treated with growth factor-loaded scaffolds, we observed a cartilage-to-bone regeneration in the skeletal defect. Five out of eight defects were completely filled with cartilage by 6 weeks. Blood vessels had invaded the cartilage, and bone was beginning to form in ossifying centers. By 3 months, these processes were well advanced, and extensive ossification was observed in 6-month samples. In contrast, the defects in control frogs showed only formation of fibrous scar tissue. This study demonstrates the utility of a Xenopus model system for tissue engineering research and that the normal in vivo mechanism of endochondral bone development and fracture repair can be mimicked in the repair of CSD with scaffolds used as growth factor delivery mechanisms.     

Association between serotonin transporter gene polymorphism and eating disorders outcome: a 6-year follow-up study

Eating disorder patients show different long-term outcomes, and trait-related alterations of serotonergic function, which might be related with the serotonin transporter (5-HTT) gene. We studied the relationships between 5-HTTLPR polymorphism, eating specific and general psychopathology and the long-term outcome of anorexia nervosa (AN) and bulimia nervosa (BN) patients. We evaluated the distribution of the functional 5-HTTLPR polymorphism in a series of 201 Italian, Caucasian, eating disorder patients (113 with AN and 88 with BN binge/purging (BP subtype) and in 150 Caucasian unrelated controls. Prior to starting an individual cognitive behavior therapy, a clinical assessment was performed by means of the structured clinical interview for DSM-IV axis I disorders and several self-report questionnaires. This assessment was repeated at the end of treatment, 3 years after the end of treatment and 3 years after the first follow-up. Diagnostic changes between AN and BN were frequent (28.3%), and the presence of depressive disorders was associated with a higher rate of diagnostic crossover during the follow-up period. The S-allele of the 5-HTTLPR genotype increases the risk susceptibility for both depressive comorbidity (OR?=?4.23; 95% CI, 1.45-12.37) and diagnostic crossover during the follow-up period in AN patients (OR = 5.04; 95% CI, 1.69-14.98). Logistic regression analyses confirmed these findings, when the interaction between genotype and psychiatric comorbidity as predictors of diagnostic instability in AN patients were taken into account. No significant association was found between 5-HTTLPR genotype and recovery. The S-allele of the 5-HTTLPR genotype increases the risk for depressive disorders comorbidity, and moderates the long-term outcome of anorectic patients.     

Prophylactic effectiveness of propolis for immunostimulation: a clinical pilot study

OBJECTIVE: The aim of this pilot investigation was to show the evidence of the prophylactic immunostimulating effectiveness caused by propolis. The immune response was determined by the measurement of the cytokine level in vivo and ex vivo (TNF-alpha, IL-6, IL-8). STUDY DESIGN: In an open prospective monocentric study, test persons received Propolis XNP. PATIENTS: 10 healthy test persons aged between 18 and 45 years, with normal weight and of either sex. INTERVENTIONS: Probands received over 13 days 500 mg Propolis XNP (2 capsules) for peroral application in the morning. MAIN OUTCOME MEASURES: Significant changes of the investigated cytokine secretion capacity during and after the treatment of propolis compared to the situation without medication. RESULTS: Although the cytokine plasma levels did not significantly change during the study, propolis led to a significant increase of both the spontaneous (TNF-alpha, p < 0. 05; IL-6, p < 0.01; IL-8, p < 0.02; IL-1beta, not detectable) and LPS(lipopolysaccaride)-induced (TNF-alpha, p < 0.001; IL-6, p < 0. 02; IL-8, p < 0.0005; IL-1beta, p < 0.05) cytokine secretion capacity following short-term ex vivo culture of peripheral blood leukocytes. Whereas the IL-6 secretion capacity further increased during the 13-day application, the IL-8 and TNF-alpha secretion reached a plateau after day 4 and the TNF-alpha secretion even decreased, but the level at day 13 was still significantly higher than at day 0. CONCLUSION: As the cytokine secretion capacity but not the cytokine plasma levels increased significantly during therapy, the prophylactic application of propolis led to a time dependent enhanced immune reactivity without undesired side effects. Copyright Copyright 1999 S. Karger GmbH, Freiburg     

Evaluation of bone healing with eggshell-derived bone graft substitutes in rat calvaria: a pilot study

The purpose of this study was to investigate the potential effectiveness of a surface-modified natural calcium carbonate, hen eggshell (ES) as a bone graft substitute. The surface characteristics, cell viability on, and osteoconductivity of, particulated ES with and without hydrothermal treatment in phosphate solutions were evaluated. Hydrothermal treatment partially converted ES to calcium-deficient hydroxyapatite (HA) with surface microstructure. MTT assay indicated higher osteoblast viability on surface-modified ES compared with a commercially available bone substitute, anorganic bovine bone (Bio-Oss, BO) (p < 0.001). Histological and histomorphometric analysis showed significantly greater new bone formation and mineralized bone-to-graft contact of surface-modified ES, especially with hydrothermally treated ES, compared with BO in 5-mm diameter calvarial defects in rats at 4 and 8 weeks of healing (p < 0.01). Complete bony bridging was more frequently found with hydrothermally treated ES. The results of this pilot study indicate the potential efficacy of surface-modified particulated hen eggshell as an osteoconductive bone substitute in a rat calvarial defect model.     

骨髓间充质干细胞修复损伤脊髓的实验及临床应用短期随访

背景：骨髓间充质干细胞治疗脊髓损伤的研究已经逐渐由动物实验过渡到临床,但其作用机制还不完全清楚。 目的：观察骨髓间充质干细胞移植对脊髓损伤大鼠脊髓功能的修复作用,并通过临床应用观察短期疗效。 方法：采用改良Allen's打击法造成Wistar大鼠脊髓损伤模型,将体外分离培养的骨髓间充质干细胞分别经尾静脉及损伤局部移植,应用改良Tarlov评分评定大鼠行为学变化,在光镜下对损伤脊髓病理切片进行对比分析。对5例脊髓损伤患者通过损伤原位注射、腰穿、静脉输注的方式行人自体骨髓间充质干细胞移植,并行神经功能及生活能力评定。 结果与结论：治疗后15 d,骨髓间充质干细胞尾静脉及损伤局部移植组大鼠运动功能评分较模型对照组显著提高;移植后7,15,30 d,脊髓病理切片显示骨髓间充质干细胞尾静脉及损伤局部移植组大鼠较模型对照组有显著恢复。临床患者骨髓间充质干细胞移植后半年神经功能及生活能力均有改善。     

Successful neurological outcome of a child with classical phenylketonuria and acute lymphoblastic leukemia: a 7-year follow-up

We report on the medical management and outcome of a child with classical phenylketonuria (PKU) who developed acute lymphoblastic leukemia (ALL). Chemotherapy began at 24 months of age. Initial problems associated with treatment lead to remarkable releases of phenylalanine, a neurotoxin. Causes included increased catabolism secondary to tumor lysis and chemotherapy, as well as infection, intermittent fasting and anorexia. Medical management involved daily monitoring of Phe levels and major changes in the amount of medical formula and the intake of protein containing foods in the diet. The child is currently in remission from ALL and has a normal neurodevelopmental outcome 7 years after the ALL diagnosis.     

Bone grafts cultured with bone marrow stromal cells for the repair of critical bone defects: an experimental study in mice

Tissue engineering of autologous bone combined with osteoprogenitor cells is a suitable strategy for filling large bone defects. The aim of this study was to evaluate the osteogenicity of a xenogenic bone graft cultured with allogenic bone marrow stromal cells (BMSC) in a mouse critical size craniotomy. Bovine trabecular bone grafts were made free of bone marrow cells or debris and were delipidated. BMSC were harvested from C57BL/6-Tg(ACTbEGFP)1Osb/J mice (GFP+ cells) and were cultured 14 days on bone grafts in control or osteogenic medium. Engineered grafts were implanted in calvarial defect in C57BL/6 mice. Four groups were studied: graft with BMSC differentiated in osteoblasts (G-Ob), graft with BMSC (G-BMSC), graft without cells (G) and no graft. Calvariae were studied 2 and 8 weeks after implantation by radiographic and histomorphometric analyses. G group: the bone ingrowth was limited to the edges of the defect. The center of the graft was filled by a fibrovascular connective tissue. G-BMSC or G-Ob groups: bone formation occurred early in the center of the defect and did not increase between 2 and 8 weeks; the newly formed woven bone was partially replaced by lamellar bone. The preoperative osteoblastic differentiation of BMSC did not allow faster and better bone regeneration. After 2 weeks, GFP+ cells were observed around the grafted bone but no GFP+ osteocyte was present in the newly formed bone. No GFP+ cell was noted after 8 weeks. However, pre-implantation culture of the biomaterial with allogenic BMSC greatly enhanced the bone regeneration.     

Incidence and clinical significance of anaerobic bacteraemia in cancer patients: a 6-year retrospective study

Recent studies have shown that anaerobes account for 0.5-9% of all episodes of bacteraemia in hospitalised patients, with variations according to geographical location and demographic characteristics, most notably age, but few data are available for cancer patients. This study investigated retrospectively the incidence of anaerobic bacteraemia in cancer patients who received non-surgical treatment over a 6-year period at a tertiary oncology centre. Gastrointestinal (27%) and haematological (29%) malignancies were the most common underlying diseases. Among 45 isolates of anaerobic bacteria recovered from 45 patients, Bacteroides spp. and Clostridium spp. were the most frequent pathogens (60% and 22%, respectively). Twenty episodes of bacteraemia were polymicrobial, most frequently with aerobic Gram-negative bacilli (18 cases). The mortality rate for patients with adequate antimicrobial therapy from the outset was 14%, compared with 63% for patients who were not treated adequately at any time.     

Cementless total knee arthroplasty with Profix: a 8- to 10-year follow-up study

A consecutive series of 115 cementless Profix (Smith and Nephew, Memphis, USA) Total Knee Arthroplasties performed in 113 patients were followed in order to determine the functional results and survivorship at 8 to 10 years. All patients were included in a prospective database and were reviewed annually until final follow-up. Patients overall satisfaction was excellent or good in 91.3% of cases. The mean Knee Society's knee and function scores increased respectively from 49.3 and 36.7 preoperatively to 93.1 and 82.2 postoperatively. The Kaplan–Meier estimate of implant survival at 10 years was 97.1%. Two patients underwent revision and were considered as failures. One patient had a fracture of the medial condyle at 4 days post-surgery, and the other was revised for aseptic loosening of the tibial component at 6 years post-surgery. On the basis of this long-term follow-up study, we can conclude that the Profix Total Knee System is effective and safe.     

Blastemal NCAM+ALDH1+ Wilms' tumor cancer stem cells correlate with disease progression and poor clinical outcome: A pilot study

BackgroundCancer Stem Cells (CSCs) have been suggested as the culprit responsible for tumor resistance to treatment and disease recurrence. Wilms' tumor (WT) is a paradigm for studying the relation between development and tumorigenesis, showing three main histological elements: undifferentiated blastema, epithelia and stroma, mimicking human kidney development. NCAM + ALDH1+ cells were previously found to contain the cancer stem like-cell population in WT. Thus far, the correlation between histologic characterization of this cell population, clinicopathologic parameters and prognostic outcome has yet been investigated in WT.ProceduresParaffin-imbedded primary WT specimens from twenty-four patients were immunostained for NCAM and ALDH1. Positivity and histologic compartment localization were determined by two independent observers, blinded to the clinical outcome. Clinicopathologic parameters and prognostic outcomes were determined based on the patients' medical records. The association of NCAM and ALDH1 co-localization with clinicopathologic characteristics was analyzed byχ²-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method.ResultsBlastemal co-localization of NCAM and ALDH1 was observed in 33% of WTs. Metastases, ICE chemotherapy protocol, blastemal predominance following preoperative chemotherapy, recurrence and patient demise were found to significantly correlate with blastemal NCAM + ALDH1+ cell staining (p < 0.05). A significant inverse correlation between blastemal double positive cells, disease-free survival and overall survival was also observed.ConclusionsWT blastemal NCAM + ALDH1+ CSCs significantly correlate with adverse clinicopathologic parameters and poorer prognosis. These results underscore the role of CSCs in disease progression. Additionally, this pilot study supports the addition of these markers for risk stratification of WTs.     

Long-term assessment of arthroscopic meniscus repair: a 13-year follow-up study

A prospective study was set up to evaluate meniscal suturing using an inside-out technique. Of an initial group of 20 patients who underwent closed meniscus repair between 1985 and 1988 using an inside-out technique, 13 were studied. All patients were subjected to a clinical examination and a magnetic resonance imaging (MRI) investigation. The findings were compared with those of their previous follow-up examination (1994). The Hospital for Special Surgery (HSS) knee rating system (R.G. Stone et al. Athroscopy 1990; 73-78) was used. The study included seven men and six women, ranging in age from 29 years to 50 years (mean age: 35 years 6 months). The mean follow-up was 13 years 2 months (11 years 11 months-15 years 4 months). Six left and seven right knees were involved. Seven patients also had an anterior cruciate ligament (ACL) injury of which one was repaired 6 years after meniscal repair. All patients obtained an HSS score of more than 75%. In all patients, the site of the previous suture was still visible on MRI mainly by small metal artefacts in the meniscus. Patients with an unrepaired ACL lesion had an early onset of arthrosis and cartilage degeneration. Meniscal suturing gives good clinical long-term results. Magnetic resonance imaging, however, showed signs of mucoid degeneration or scar tissue in 46% of the patients.     

Geleophysic dysplasia: 7-year follow-up study of a patient with an intermediate form

Geleophysic dysplasia (MIM *231050) is a rare autosomal recessive disorder, characterized by short stature with short limbs, brachydactyly, joint contractures, and a good-natured facial appearance. Infiltration of liver and cardiac leaflets has been reported in some patients. Based on the clinical picture and the detection of lysosome-like inclusions in hepatocytes, tracheal mucosa, chondrocytes, and skin fibroblasts, the underlying cause of the conditions is considered to be a generalized lysosomal storage defect. We report on a new case born to consanguineous parents, first observed at age 8 months, and for whom a 7-year follow-up is available. Am. J. Med. Genet. 86:82–85, 1999. © 1999 Wiley-Liss, Inc.     

自体骨髓间充质干细胞载体复合物修复骨缺损的组织学观察

背景：在骨缺损修复过程中,从修复质量、免疫排斥和疾病传播等多方面来衡量,自体骨都是最佳的选择,但来源有限且取骨区可能产生并发症,给骨缺损的修补及自体骨移植临床应用带来了很大局限。 目的：以含自体骨髓间充质干细胞脱钙骨载体复合支架材料植入骨缺损的同时,向植入处微环境内添加碱性成纤维细胞生长因子等因素,从而达到增强骨修复能力,改进修复效果的目的。 方法：选择3月龄新西兰大耳白兔45只,建立双侧前臂桡骨中下段骨-骨膜缺损模型,然后将实验兔等分为3组：实验组、对照组和空白组,均于左侧髂骨和股骨转子处抽取骨髓,分离培养扩增骨髓间充质干细胞后,与不同材料体外复合,植入兔桡骨干10 mm缺损处。实验组兔缺损处植入骨髓间充质干细胞、脱钙骨、藻酸钙、碱性成纤维细胞生长因子、维生素C;对照组兔缺损处植入骨髓间充质干细胞、脱钙骨、藻酸钙;空白组兔双侧缺损处均不植入任何材料,自然愈合。 结果与结论：植入后30,60,90 d各组之间组织学检查新骨生成速度、生成量差异均有显著性意义。实验组兔缺损修复部位骨痂和移植物化骨及材料降解明显快于对照组和空白组;但对照组和空白组兔缺损修复部位残存物明显多于实验组。实验组兔骨缺损以多点方式直接成骨,对照组和空白组则从两端以“爬行替代”方式成骨。空白组兔自然愈合后90 d骨缺损均无愈合。说明植入体外培养移植物的同时向该植入微环境添加碱性成纤维细胞生长因子和维生素C等有利骨修复,提高骨损伤的愈合。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

CD23+ mantle cell lymphoma: a clinical pathologic entity associated with superior outcome compared with CD23- disease

Mantle cell lymphoma (MCL) commonly lacks expression of CD23. However, a significant minority of MCLs express CD23, as assessed by flow cytometric immunophenotyping (FCIP). The aims of our study were to investigate the expression of CD23 by FCIP in patients with MCL and to correlate CD23 expression with pathologic and clinical parameters, including outcome. We studied 53 patients with untreated MCL who had CD23 expression determined by FCIP. At diagnosis, 14 MCLs (26%) were CD23+ at all tissue sites, whereas 33 (62%) were CD23-, and 6 (11%) had discordant CD23 expression among different tissue sites. Patients with CD23- MCL had extranodal disease more commonly compared with patients with CD23+ MCL. Moreover, with 57-month median follow-up, the 4-year event-free and overall survival rates for CD23+ MCL were 45% and 75%, respectively, compared with 19% and 51% for CD23- MCL. In multivariate Cox regression analysis, CD23 status and leukemic-phase MCL were the most important factors predicting outcome.     

Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study

The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles were observed. Blood and urine routine test, liver function, electrocardiogram, chest radiography and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155) and CA199, were assayed before and 1, 2, 4 and 6 years after MSCs transplantation. All the patients completed two times of MSCs infusions. One patient had mild dizzy and warm sensation 5 min after MSCs infusion, and the symptoms disappeared quickly. No other adverse event, including fluster, headache, nausea or vomit, was observed. There was no change in peripheral white blood cell count, red blood cell count and platelet number in these patients after followed up for 6 years. Liver functional analysis showed that serum alanine aminotransferase, glutamic-oxalacetic transaminase, total bilirubin and direct bilirubin remained in normal range after MSCs infusions. No newly onset abnormality was detected on electrocardiogram and chest radiography. Moreover, we found no rise of serum tumor markers, including AFP, CEA, CA125 and CA199, before and 6 years after MSCs infusions. Our long-term observational study demonstrated a good safety profile of allogeneic UC MSCs in SLE patients.