Dingyang Liu

Transplantation of hUC-MSCs seeded collagen scaffolds reduces scar formation and promotes functional recovery in canines with chronic spinal cord injury.

Spinal cord injury (SCI) can lead to locomotor deficits, and the repair of chronic SCI is considered one of the most challenging clinical problems. Although extensive studies have evaluated treatments for acute SCI in small animals, comparatively fewer studies have been conducted on large-animal SCI in the chronic phase, which is more clinically relevant. Here, we used a collagen-based biomaterial, named the NeuroRegen scaffold, loaded with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a canine chronic SCI model. To generate chronic SCI, the T8 spinal cord segment was removed by complete transection of the spinal cord. Two months later, glial scar tissue was removed and a NeuroRegen scaffold was transplanted into the lesion area. Functionalized NeuroRegen scaffold implantation promoted both locomotor recovery and endogenous neurogenesis in the lesion area. Moreover, some newly generated neurons successfully matured into 5-HT-positive neurons at 1 year post-injury. In addition, many regenerated axon fibers in the lesion area exhibited remyelination and synapse formation at 1 year post-injury in the functionalized NeuroRegen scaffold group. In conclusion, the NeuroRegen scaffold functionalized with hUC-MSCs is a promising potential therapeutic approach to chronic SCI that promotes neuronal regeneration, reduces glial scar formation, and ultimately improves locomotor recovery.

Identification of ABCG2+ cells in nasopharyngeal carcinoma cells

Tumor stem cells are a small subset of tumor cells with the ability of self-renewal and differentiation and are regarded as a cause of tumor growth and recurrence. Previously we have shown that stem-like label-retaining cells (LRCs) can be detected in nasopharynx, tongue, esophagus and xenograft tumors formed by nasopharyngeal carcinoma (NPC) cell lines (5–8F, 6–10B and TMNE). The present study aimed to identify ABCG2+ cells in 5–8F NPC cells and compare their tumorigenic potential with ABCG2− cells, expecting that we can obtain insight into the mechanism of the differential phenotypes of ABCG2+ and ABCG2− cells. By using magnetic cell sorting (MACS) method, we isolated ABCG2+ cells and ABCG2− cells from 5–8F cells. Among these two subpopulations and unsorted 5–8F cells, the rate of ABCG2+ cells at G1 phase was highest, while the rate of ABCG2− cells at S phase was highest, indicating that ABCG2+ cells were mostly quiescent. However, ABCG2+ cells showed lower cloning efficiency and tumorigenicity than ABCG2− cells. We also used Affymetrix U133 plus 2.0 human whole genome expression chip to identify the gene expression profile of ABCG2+ and ABCG2− cells and found that both subpopulations expressed some stem cell associated genes, e.g., PSCA, ABCG2 and ALPI were expressed in ABCG2+ cells, and K19, integrin α6, integrin β4, CD44 and K14 were expressed in ABCG2− cells, suggesting there were stem cells in both ABCG2+ and ABCG2− cells. Our data demonstrated that there exist ABCG2+ cells in NPC cells, but ABCG2 alone is not sufficient for isolating cancer stem cells in 5–8F NPC cells.

HESRG: a novel biomarker for intracranial germinoma and embryonal carcinoma

The novel stem cell-related gene, HESRG, was first identified by our group, and its expression pattern in human tumors remains unknown. In this study, we used RT-PCR to systematically investigate the expression of HESRG in various types of intracranial tumors and found that HESRG was expressed only in germinoma and embryonal carcinoma, but hardly at all in other types of brain tumors. Real-time PCR results further confirmed this expression pattern. Subsequently, we tested 134 intracranial non-germ cell tumors and 64 intracranial germ cell tumors by immunohistochemistry. Our results showed that HESRG was expressed strongly and diffusively in the nuclei of tumor cells in intracranial germinoma and embryonal carcinoma as well as in human embryonic stem cells. No positive staining signal was observed in any other type of intracranial tumors. In germinomas, 25 of 31 showed intensive (3+) expression, four cases showed moderate (2+) immunostaining and the remaining 2 cases showed weak (1+) immunostaining. In embryonal carcinoma, 6 of 9 showed intensive (3+) immunostaining and 3 of 9 showed moderate (2+) immunostaining. These results suggest that HESRG is a novel, sensitive and specific biomarker for intracranial germinoma and embryonal carcinoma.

ALDH1 expression is correlated with pathologic grade and poor clinical outcome in patients with astrocytoma.

Aldehyde dehydrogenase 1 (ALDH1), a detoxifying enzyme, is a stem-like cell marker, but its expression pattern and clinical significance in astrocytoma remain unclear. In this study, we used immunohistochemical analysis to systematically investigate the expression of ALDH1 in 76 astrocytomas of different pathological grade and seven samples of normal brain tissues. We found that ALDH1 was expressed in some of the astrocytomas but was not detected in normal brain tissues. The proportion of ALDH1-expressing cells was positively correlated with the pathological grade of the astrocytomas, but not with patient age, sex or tumor size. We also collected detailed follow-up data and analyzed the correlation of ALDH1 expression with overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analysis. We found that the proportion of ALDH1-positive cells was an independent prognostic factor for PFS and OS. These results show that ALDH1 is expressed in astrocytoma, and that its expression is correlated with pathological grade and patient survival.

Transcriptional repression of FOXO1 by KLF4 contributes to glioma progression.

In this study, our findings indicated that FOXO1 expression frequently decreased in glioma tissues and cells. FOXO1 expression decrease correlated with glioma progression and predicted a worse overall survival of glioma patients. Restored FOXO1 expression inhibited glioma cells invasion and suppressed glioma cells proliferation in vitro and growth in vivo. Additionally, we found that KLF4 expression frequently increased in glioma tissues and negatively correlated with FOXO1 expression. Bioinformatics analysis and experimental results indicated that KLF4 transcriptionally repressed FOXO1 expression in glioma cells. Moreover, KLF4 expression increase correlated with glioma progression and predicted a poorer overall survival of glioma patients. KLF4 knockdown attenuated glioma cells invasion and growth. These data provide a rationale for targeted intervention on KLF4-FOXO1 signaling pathway to suppress glioma progression.

The expression of moesin in astrocytoma: correlation with pathologic grade and poor clinical outcome

Moesin, a member of the ERM family, acts as a linker between the actin cytoskeleton and the plasma membrane and plays a key role in the control of cell morphology, motility, adhesion and other processes of tumourigenesis. The expression pattern and clinical significance of moesin in astrocytoma remain unknown. In this study, we used RT-PCR to systematically investigate the expression of moesin in 49 astrocytomas of different pathological grade and 6 normal brain tissues. We found that the mRNA expression levels of moesin in astrocytomas were significantly higher in comparison with normal brain tissues. Furthermore, moesin up-regulation was correlated with pathological grade of astrocytomas. Subsequently, we tested 112 astrocytomas and 14 normal brain tissues by immunohistochemistry. Similar results were also confirmed. Univariate and multivariate survival analysis were used to determine the correlations of moesin expression with overall survival and progression-free survival. Our results showed the expression of moesin was strongly negatively correlated with the patient progression-free survival and overall survival. These results suggest moesin protein involved in the genesis and progression of astrocytomas and might be regarded as an independent predictor of poor prognosis.

Intramedullary thoracic spinal cord meningioma: a rare case report and review of the literature.

A 33-year-old male presented with a thoracic spinal intramedullary meningioma manifesting as bilateral asymmetric progressive weakness in the lower extremities. Preoperative magnetic resonance imaging (MRI) showed an intramedullary mass at the T1-T3 level. Intraoperative inspection found that the spinal cord was markedly swollen with a normal surface while dural attachment was not confirmed. Gross total removal of the tumor was achieved. The morphologic and immunohistochemical findings were compatible with the diagnosis of meningioma. Postoperatively, the patient recovered from preoperative paraplegia. Although extremely rare, meningiomas should be considered when diagnosing intramedullary tumors.

AS‐IL6 promotes glioma cell invasion by inducing H3K27Ac enrichment at the IL6 promoter and activating IL6 transcription

Interleukin‐6 (IL‐6) is widely expressed in a variety of malignant tumors; thus, targeting the IL‐6/STAT3 pathway represents a promising therapeutic strategy for malignant cancers. In this study, we identified a noncoding RNA, AS‐IL6, which is transcribed antisense to IL6 and induces IL6 expression in glioma cells. Knockdown of AS‐IL6 attenuates LPS‐induced IL6 transcription. Interestingly, AS‐IL6 does not change IL6 mRNA stability, but induces the enrichment of histone H3 acetylated at lysine 27 (H3K27Ac) at the IL6 promoter. In addition, we found that depletion of AS‐IL6 inhibits the invasive ability of glioblastoma cells, while treatment of cells with recombinant IL6 reverses this effect. Our results reveal a novel mechanism of IL6 regulation and demonstrate an oncogenic role for AS‐IL6 in glioma cells.