MicroRNAs (miRs) are a class of small non-coding RNAs that function as mediators of gene expression. Dysregulations of miRs have been implicated in the development and progression of glioma. In the present study, we investigated the role of miR-133b in mediating the proliferation and invasion of glioma cells, and the potential mechanism. Real-time RT-PCR results showed that miR-133b expression was significantly decreased in glioma tissues compared with normal brain tissues. Luciferase reporter assay further identified silent information regulator 1 (Sirt1) as a novel direct target of miR-133b in glioma U87 cells. Overexpression of miR-133b suppressed Sirt1 expression and reduced the proliferation and invasion of U87 cells, which could be partly rescued by forced expression of Sirt1. In addition, the Sirt1 mRNA level was significantly higher in glioma tissues than in normal brain tissues, and was inversely correlated with miR-133b level in glioma tissues. In summary, our study sheds light on the regulatory mechanism of miR-133b in glioma growth and metastasis via direct mediation of Sirt1 expression, and suggests that Sirt1 may serve as a potential therapeutic target for glioma.

Objective: Investigate the impact of diaphragm sellae competence on surgical outcomes and risk factors for postoperative hypothalamic injury (HI) in patients undergoing endoscopic transsphenoidal surgery (ETS) for infra-diaphragmatic craniopharyngiomas (ICs). Methods: A retrospective analysis of 54 consecutive patients (2016-2023) with ICs treated by ETS was conducted. All tumors originated from the sellar region inferior to the diaphragm sellae and were classified into two subtypes in terms of diaphragm sellae competence: IC with competent diaphragm sellae (IC-CDS) and IC with incompetent diaphragm sellae (IC-IDS). Clinical features, intraoperative findings, and follow-up data were compared between subtypes. Postoperative HI was assessed using a magnetic resonance imaging-based scoring system. Results: Fifty-four patients (29 males, 25 females) were included in this study, with 12 (22.2%) under 18 years old. Overall, 35 cases were IC-CDS, while 19 were IC-IDS. Compared with IC-CDS, patients with IC-IDS tended to have hormone hypofunction before surgery (p = 0.03). Tumor volume in IC-IDS group (9.0 ± 8.6 cm3) was also higher than that in IC-CDS group (3.3 ±3.4 cm, p = 0.011). Thirty-seven patients underwent standard endoscopic transsphenoidal approach (SEA) and 17 underwent an extended endoscopic transsphenoidal approach (EEA). Gross total resection (GTR) was achieved in 50 cases (92.6%). Postoperative CSF leak was observed in four patients (7.4%). Permanent diabetes insipidus (DI) occurred in 13 patients (27.7%), six in IC-CDS and seven in IC-IDS. Postoperative HI occurred in 38.9% of patients. Univariate analysis revealed that large tumor size (p = 0.014), prior hypopituitarism (p = 0.048) and IC-IDS (p < 0.001) were significantly associated with postoperative HI. Multivariate analysis revealed that IC- IDS was the sole predictor of postoperative HI. Conclusion: To our knowledge, this is the largest case series in the literature to describe IC resected by endoscopic surgery in a single institution. Classification based on diaphragm sellae competence highlights distinct clinical features and surgical outcomes between IC-CDS and IC-IDS subtypes. Notably, IC-IDS is an independent risk factor for postoperative HI. Preoperative identification of subtype can guide surgical strategy and potentially minimize complications.

Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.

Background This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA). Methods We enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment). Results The incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20–6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III. Conclusions Preoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.

Objective To evaluate the long-term outcomes and safety of endoscopic transsphenoidal surgery (ETS) in recurrent and residual pituitary adenomas (rrPAs), as well as the predictors of gross total resection (GTR) and intraoperative CSF leakage. Furthermore, to compare outcomes and complications with non-rrPAs cohort. Methods Clinical and radiological characteristics of patients with rrPAs who underwent ETS were collected between 2017 and 2020. Data of patients with non-rrPAs were collected from 2019 to 2020. Logistic regression analyses were performed to investigate the factors influencing gross total resection (GTR) and intraoperative CSF leakage. Between-group comparisons of outcomes and complications were performed through propensity score analysis. Results We enrolled 73 patients with rrPAs. GTR was achieved in 41 (56.1%) cases; further, GTR or near-total resection was achieved in 93.2% of patients. The mean tumor volumes for GTR and non-GTR cases were 6.2 ±7.2 cm3 and 11.1 ±9.1 cm3, respectively. Multivariate regression analysis of the GTR rate in patients with rrPAs revealed that Knosp grade was an independent factor (odds ratio [OR] = 0.324; p=0.005). Moreover, previous transcranial surgery and non-functional pituitary adenomas were risk factors for intraoperative CSF leakage in patients with rrPAs (OR=6.450, p=0.019 and OR=7.472, p=0.012, respectively). After propensity score matching, There was no significant difference in the GTR rate between patients with rrPAs and patients with non-rrPAs. Contrastingly, patients with rrPAs had a higher rate of intraoperative CSF leakage and longer postoperative hospital stay than patients with non-rrPAs. During the follow-up, vision improved in 9 (22.0%) and 24 (62.5%) patients with rrPAs and non-rrPAs, respectively. Although there was a trend that reoperation of rrPAs involved a lower hypopituitarism recovery rate and biochemical remission rate, as well as a higher hypopituitarism rate, there was no statistically significant between-group difference. Conclusions Knosp grade was an independent factor for GTR in endoscopic transsphenoidal surgery in patients with rrPAs. Previous transcranial surgery and non-functional PAs were risk factors for intraoperative CSF leakage. Although associated with longer hospital stay, rrPAs did not associate with lower GTR rate or more frequent postoperative complications than non-rrPAs cohort.

Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.

Gliomas are aggressive tumors in the central nervous system and glioblastoma is the most malignant type. Ferroptosis is a programmed cell death that can modulate tumor resistance to therapy and the components of tumor microenvironment. However, the relationship between ferroptosis, tumor immune landscape, and glioblastoma progression is still elusive. In this work, data from bulk RNA-seq analysis, single cell RNA-seq analysis, and our own data (the Xiangya cohort) are integrated to reveal their relationships. A scoring system is constructed according to ferroptosis related gene expression, and high scoring samples resistant to ferroptosis and show worse survival outcome than low scoring samples. Notably, most of the high scoring samples are aggressive glioblastoma subtype, mesenchymal, and classical, by calculating RNA velocity. Cross-talk between high scoring glioblastoma cells and immunocytes are explored by R package ‘celltalker’. Ligand–receptor pairs like the TRAIL or TWEAK signaling pathway are identified as novel bridges implying how ferroptosis modulate immunocytes’ function and shape tumor microenvironment. Critically, potential drugs target to high scoring samples are predicted, namely, SNX2112, AZ628, and bortezomib and five compounds from the CellMiner database. Taken together, ferroptosis associates with glioblastoma aggressiveness, cross-talk with immunocytes and offer novel chemotherapy strategy.

CD68 plays a critical role in promoting phagocytosis; however, the function of CD68 in tumor immunity and prognosis remains unknown. We analyzed CD68 expression among 33 tumor and normal tissues from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. The relationship between CD68 expression and cancer prognosis, immune infiltration, checkpoint markers, and drug response was explored. Upregulated CD68 levels were observed in various cancer types, which were verified through tumor tissue chips using immunohistochemistry. High levels of CD68 in tumor samples correlated with an adverse prognosis in glioblastoma, kidney renal clear cell carcinoma, lower-grade glioma, liver hepatocellular carcinoma, lung squamous cell carcinoma, thyroid carcinoma, and thymoma and a favorable prognosis in kidney chromophobe. The top three negatively enriched Kyoto Encyclopedia of Genes and Genomes terms in the high CD68 subgroup were chemokine signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecule cams. The top negatively enriched HALLMARK terms included complement, allograft rejection, and inflammatory response. A series of targeted drugs and small-molecule drugs with promising therapeutic effects were predicted. The clinical prognosis and immune infiltration of high expression levels of CD68 differ across tumor types. Inhibiting CD68-dependent signaling could be a promising therapeutic strategy for immunotherapy in many tumor types.

目的 分析垂体腺瘤卒中的危险因素.方法 选取2020年6月-2021年12月中南大学湘雅医院诊治的50例垂体腺瘤患者,根据影像及手术资料分为垂体瘤合并卒中组(23例)和垂体瘤不合并卒中组(27例),分析卒中因素.结果 多因素Logistic分析显示垂体瘤手术切除史、垂体瘤最大直径大是其影响因素.其中有1例伽玛刀治疗后出现肿瘤亚临床卒中的特殊病例.结论 有垂体瘤手术切除史、垂体瘤最大直径大的患者是发生卒中的高危因素,伽玛刀治疗后出现影像学上的肿胀,可能是亚临床卒中.

Glioblastomas are the most malignant brain tumors, whose progress was promoted by aberrate aerobic glycolysis. The immune environment was highly engaged in glioblastoma formation, while its interaction with aerobic glycolysis remained unclear. Herein, we build a 7-gene Glycolytic Score (GS) by Elastic Net in the training set and two independent validating sets. The GS predicted malignant features and poor survival with good performances. Immune functional analyses and Cibersort calculation identified depressed T cells, B cells, natural killer cells immunity, and high immunosuppressive cell infiltration in the high-GS group. Also, high expressions of the immune-escape genes were discovered. Subsequently, the single-cell analyses validated the glycolysis-related immunosuppression. The functional results manifested the high-GS neoplastic cells’ association with T cells, NK cells, and macrophage function regulation. The intercellular cross-talk showed strong associations between high-GS neoplastic cells and M2 macrophages/microglia in several immunological pathways. We finally confirmed that ENO1 , the key gene of the GS, promoted M2 microglia polarization and glioblastoma cell malignant behaviors via immunofluorescence, clone formation, CCK8, and transwell rescue experiments. These results indicated the interactions between cancerous glycolysis and immunosuppression and glycolysis’ role in promoting glioblastoma progression. Conclusively, we built a robust model and discovered strong interaction between GS and immune, shedding light on prognosis management improvement and therapeutic strategies development for glioblastoma patients.

Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.

Because of the limited treatment strategy of gliomas, the key of diagnosis and treatment is finding new molecular biomarkers. Here, we explored the potential of β2-microglobulin (B2M) to serve as a hopeful candidate for immunotherapy or diagnostic biomarker in gliomas. The genomic profiles, clinical characteristics, and immune signatures were analyzed based on TCGA and CGGA databases. We carried out the whole statistical analyses using R project. High B2M expression correlated with worse prognosis. Somatic mutations of gliomas with high B2M expression are associated with PTEN deletion and EGFR amplification. Isocitrate dehydrogenase (IDH) mutations accounted for 82% in gliomas with low B2M expression. In addition, B2M positively correlated with ESTIMATE scores, interacted with infiltrating immune and stromal cell types. B2M also suppressed anti-tumor immunity through immune related processes. Meanwhile, B2M was associated with immune checkpoint molecules and inflammatory activities. Finally, functional annotation of the identified B2M related genes verified that B2M was a potential candidate for immunotherapy. We confirmed that B2M played a critical role in tumor progression, patient prognosis and immunotherapy of gliomas.

Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment.Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis.Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival.Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.

Objective To summarize the key points of neuroendoscopic transcranial resection for cerebellopontine angle (CPA) tumors. Methods Twenty⁃eight patients with CPA tumors diagnosed and treated in Xiangya Hospital Central South University from January 2019 to December 2020 were included, and all of them underwent neuroendoscopic transcranial surgery to remove CPA tumors. Results All the 28 patients were successfully treated with neuroendoscopic transcranial resection of tumors in CPA region, and the tumors were totally removed. After operation, 9 cases of acoustic neuroma, 8 cases of meningioma, 9 cases of cholesteatoma, one case of hemangioblastoma, and one case of trigeminal neurinoma were confirmed by postoperative pathology. Postoperative facial nerve function was grade Ⅲ in 3 cases, grade Ⅱ in 6 cases, and grade Ⅰ in 19 cases. One patient had no obvious recovery of auditory nerve function injury, and 2 patients had dizziness, vertigo and nausea after operation. No complications such as cerebrospinal fluid leakage, meningitis and incision infection occurred, and no death occurred. At 3 months of follow ⁃ up, no tumor recurrence was seen on MRI, and no new neurological symptoms occurred. Conclusions Neuroendoscopic transcranial resection of CPA tumors has many advantages, but also has some shortcomings, and has a good development in the future.

BACKGROUND:Autophagy and long non-coding RNA (lncRNA) play a critical role in tumor progression and microenvironment. However, the role of autophagy-related lncRNAs (ARLs) in glioma microenvironment remains unclear.METHODS:A total of 988 diffuse glioma samples were extracted from TCGA and CGGA databases. Consensus clustering was applied to reveal different subgroups of diffuse gliomas. Kaplan-Meier analysis was used to evaluate survival differences between groups. The infiltration of immune cells was estimated by ssGSEA, TIMER, and CIBERSORT algorithms. The construction of ARL signature was conducted using principal component analysis.RESULTS:Consensus clustering revealed two clusters of diffuse gliomas, in which cluster 1 was associated with poor prognosis and enriched with malignant subtypes of gliomas. Moreover, cluster 1 exhibited high apoptotic and immune characteristics, and it had a low purity and high infiltration of several immune cells. The constructed ARL signature showed a promising accuracy in predicting the prognosis of glioma patients. ARL score was significantly elevated in the malignant subtype of glioma and the high ARL score indicated a poor prognosis. Besides, the high ARL score notably indicated low tumor purity and high infiltration of macrophages and neutrophils.CONCLUSION:Our study developed and validated a novel ARL signature for the classification of diffuse glioma, which was closely associated with glioma immune microenvironment and could serve as a promising prognostic biomarker for glioma patients.

Purpose Glioblastoma (GBM) is the most common and deadly brain tumor. We aimed to reveal potential prognostic GBM marker genes, elaborate their functions, and build an effective a prognostic model for GBM patients. Methods Through data mining of The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we screened for significantly differentially expressed genes (DEGs) to calculate risk scores for individual patients. Published data of somatic mutation and copy number variation profiles were analyzed for distinct genomic alterations associated with risk scores. In addition, single-cell sequencing was used to explore the biological functions of the identified prognostic marker genes. By combining risk scores and other clinical features, we built a comprehensive prognostic GBM model. Results Seven DEGs (CLEC5A, HOXC6, HOXA5, CCL2, GPRASP1, BSCL2 and PTX3) were identified as being prognostic for GBM. Expression of these genes was confirmed in different GBM cell lines using real-time PCR. Risk scores calculated from the seven DEGs revealed prognostic value irrespective of other clinical factors, including IDH mutation status, and were negatively correlated with TP53 expression. The prognostic genes were found to be associated with tumor proliferation and progression based on pseudo-time analysis in neoplastic cells. A final prognostic model was developed and validated with a good performance, especially in geriatric GBM patients. Conclusions Using genetic profiles, age, IDH mutation status, and chemotherapy and radiotherapy, we constructed a comprehensive prognostic model for GBM patients. The model has a good performance, especially in geriatric GBM patients.

Because the study population with gliosarcoma (GSM) is limited, the understanding of this disease is insufficient. In this study, the authors aimed to determine the clinical characteristics and independent prognostic factors influencing the prognosis of GSM patients and to develop a nomogram to predict the prognosis of GSM patients after craniotomy. A total of 498 patients diagnosed with primary GSM between 2004 and 2015 were extracted from the 18 Registries Research Data of the Surveillance, Epidemiology, and End Results (SEER) database. The median disease-specific survival (DSS) was 12.0 months, and the postoperative 0.5-, 1-, and 3-year DSS rates were 71.4%, 46.4% and 9.8%, respectively. We applied both the Cox proportional hazards model and the decision tree model to determine the prognostic factors of primary GSM. The Cox proportional hazards model demonstrated that age at presentation, tumour size, metastasis state and adjuvant chemotherapy (CT) were independent prognostic factors for DSS. The decision tree model suggested that age <71 years and adjuvant CT were associated with a better prognosis for GSM patients. The nomogram generated via the Cox proportional hazards model was developed by applying the rms package in R version 3.5.0. The C-index of internal validation for DSS prediction was 0.67 (95% confidence interval (CI), 0.63 to 0.70). The calibration curve at one year suggested that there was good consistency between the predicted DSS and the actual DSS probability. This study was the first to develop a disease-specific nomogram for predicting the prognosis of primary GSM patients after craniotomy, which can help clinicians immediately and accurately predict patient prognosis and conduct further treatment.

Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.

Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.