Hepatocellular carcinoma (HCC) is a cancer with extremely high mortality. Epithelial‐mesenchymal transition (EMT) may play an important role in the occurrence, invasion and prognosis of HCC; however, ...its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC. We first proposed a quantitative metric of EMT activity, the EMT score. After applying this metric to 20 datasets from the Integrative Molecular Database of Hepatocellular Carcinoma, the Cancer Genome Atlas, and the Gene Expression Omnibus, we explored the ability of the EMT score to stratify across sample types. We then applied the EMT score for survival analysis and to differentiate patients with/without vascular invasion to test its prognostic value. We also collected and calculated data on the abundance of immune cells and immune cell markers in HCC and investigated their correlations with EMT scores. Finally, we synthesized and analyzed 20 datasets and constructed an EMT‐gene‐immune linkage network. The results showed higher EMT scores in HCC samples than in cirrhotic and normal livers. The cases with higher EMT scores also showed poorer performance in terms of prognostic factors such as vascular invasion and overall survival time. Our research demonstrated a broad correlation between EMT and the tumor immune microenvironment, and we uncovered multiple potential linkers associated with both EMT and immunity. Studying EMT has clinical relevance and high diagnostic and prognostic value for HCC.
Epithelial‐mesenchymal transition (EMT) may play an important role in the occurrence, invasion, and prognosis of hepatocellular carcinoma (HCC); however, its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC.
Summary
Aims
The objective of this study was to analyze the efficacy of polypyrrole/polylactic acid (PPy/PLA) nanofibrous scaffold cotransplanted with bone marrow stromal cells (BMSCs) in promoting ...the functional recovery in a rat spinal cord injury (SCI).
Methods
Female Sprague‐Dawley rats were randomly divided into three groups (n = 18/group): control group, PPy/PLA group, and PPy/PLA/BMSCs group. The SCI was induced in all rats. Consequently, rats in PPy/PLA/BMSCs group were transplanted with 1 × 105 BMSCs after implantation of PPy/PLA, while those in the PPy/PLA group were implanted with PPy/PLA only; no implantation was performed in the control group. Six weeks after surgery, immunofluorescence microscopy, electron microscope, and polymerase chain reaction (PCR) techniques were performed to assess the changes in the injured spinal cord tissues.
Results
Electrophysiology and locomotor function testing suggested that PPy/PLA nanofibrous scaffold cotransplanted with BMSCs could promote the functional recovery of the spinal cord. Six weeks after the operation, lower amount of scar tissue was found in the PPy/PLA group compared with the control group. Abundant neurofilament (NF) and neuron‐specific marker (NeuN) positive staining, and myelin formations were detected in the injured area. In addition, the transplantation of BMSCs not only improved the efficacy of PPy/PLA but also managed to survive well and was differentiated into neural and neuroglial cells.
Conclusions
The implantation of PPy/PLA nanofibrous scaffold and BMSCs has a great potential to restore the electrical conduction and to promote functional recovery by inhibiting the scar tissue formation, promoting axon regeneration, and bridging the gap lesion.
Abstract Neural stem cells (NSCs) cultured on glass surfaces modified by different chemical groups, including hydroxyl (–OH), sulfonic (–SO3 H), amino (–NH2 ), carboxyl (–COOH), mercapto (–SH) and ...methyl (–CH3 ) groups, are shown here to commit to phonotypes with extreme sensitivity to surface chemical groups. The adhering NSCs at the level of single cells exhibited morphological changes in response to different chemical groups. NSCs on –SO3 H surfaces had the largest contact area and the most flattened morphology, while those on –CH3 surfaces exhibited the smallest contact area and the most rounded morphology. After 5 days of culture, the migration of NSCs from their original aggregates onto these test surfaces followed the trend: –NH2 >–COOH = –SH≫–SO3 H>–CH3 >–OH. The expression of specific markers, including nestin, β-Tubulin-III, glial fibrillary acidic protein and O4, were used to examine NSCs lineage specification. The –SO3 H surfaces favored NSCs differentiation into oligodendrocytes, while NSCs in contact with –COOH, –NH2 , –SH and –CH3 had the ability to differentiate into neurons, astrocytes and oligodendrocytes. Compared to –COOH surfaces, –NH2 seemed to promote neuronal differentiation. These chemically modified surfaces exhibited regulation of NSCs on adhesion, migration and differentiation potential, providing chemical means for the design of biomaterials to direct NSCs lineage specification for neural tissue engineering.
The nerve fibre circuits around a lesion play a major role in the spontaneous recovery process after spinal cord hemisection in rats. The aim of the present study was to answer the following ...question: in the re-control process, do all spinal cord nerves below the lesion site participate, or do the spinal cord nerves of only one vertebral segment have a role in repair?
First we made a T7 spinal cord hemisection in 50 rats. Eight weeks later, they were divided into three groups based on distinct second operations at T7: ipsilateral hemisection operation, contralateral hemisection, or transection. We then tested recovery of hindlimbs for another eight weeks. The first step was to confirm the lesion had role or not in the spontaneous recovery process. Secondly, we performed T7 spinal cord hemisections in 125 rats. Eight weeks later, we performed a second single hemisection on the ipsilateral side at T8-T12 and then tested hindlimb recovery for another six weeks.
In the first part, the Basso, Beattie, Bresnahan (BBB) scores and the electrophysiology tests of both hindlimbs weren't significantly different after the second hemisection of the ipsilateral side. In the second part, the closer the second hemisection was to T12, the more substantial the resulting impairment in BBB score tests and prolonged latency periods.
The nerve regeneration from the lesion area after hemisection has no effect on spontaneous recovery of the spinal cord. Repair is carried out by all vertebrae caudal and ipsilateral to the lesion, with T12 being most important.
Artificial extracellular matrices play important roles in the regulation of stem cell behavior. To generate materials for tissue engineering, active functional groups, such as amino, carboxyl, and ...hydroxyl, are often introduced to change the properties of the biomaterial surface. In this study, we chemically modified coverslips to create surfaces with different amino densities and investigated the adhesion, migration, and differentiation of neural stem cells (NSCs) under serum-free culture conditions. We observed that a higher amino density significantly promoted NSCs attachment, enhanced neuronal differentiation and promoted excitatory synapse formation in vitro. These results indicate that the amino density significantly affected the biological behavior of NSCs. Thus, the density and impact of functional groups in extracellular matrices should be considered in the research and development of materials for tissue engineering
To study the transplantation efficacy of neural stem cells (NSCs) and Schwann cells (SC) in a rat model of spinal cord contusion injury.
Multipotent neural stem cells (NSCs) and Schwann cells were ...harvested from the spinal cords of embryonic rats at 16 days post coitus and sciatic nerves of newborn rats, respectively. The differential characteristics of NSCs in vitro induced by either serum-based culture or co-culture with SC were analyzed by immunofluorescence. NSCs and SCs were co-transplanted into adult rats having undergone spinal cord contusion at T9 level. The animals were weekly monitored using the Basso-Beattie-Bresnahan locomotor rating system to evaluate functional recovery from contusion-induced spinal cord injury. Migration and differentiation of transplanted NSCs were studied in tissue sections using immunohistochemical staining.
Embryonic spinal cord-derived NSCs differentiated into a large number of oligodendrocytes in serum-based culture upon the withdrawal of mitogens. In cocultures with SCs, NSCs differentiated into neuron more readily. Rats with spinal cord contusion injury which had undergone transplantation of NSCs and SCs into the intraspinal cavity demonstrated a moderate improvement in motor functions.
SC may contribute to neuronal differentiation of NSCs in vitro and in vivo. Transplantation of NSCs and SCs into the affected area may be a feasible approach to promoting motor recovery in patients after spinal cord injury.
To investigate the effect of rat Schwann cell secretion on the proliferation and differentiation of human embryonic neural stem cells (NSCs).
The samples were divided into three groups. In Group One, ...NSCs were cultured in DMED/F12 in which Schwann cells had grown for one day. In Group Two, NSCs and Schwann cells were co-cultured. In Group Three, NSCs were cultured in DMEM/F12. The morphology of NSCs was checked and beta-tubulin, GalC, hoechst 33342 and GFAP labellings were detected.
In Group One, all neural spheres were attached to the bottom and differentiated. The majority of them were beta-tubulin positive while a few of cells were GFAP or GalC positive. In Group Two, neural spheres remained undifferentiated and their proliferation was inhibited in places where Schwann cells were robust. In places where there were few Schwann cells, NSCs performed in a similar manner as in Group One. In Group Three, the cell growth state deteriorated day after day. On the 7th day, most NSCs died.
The secretion of rat Schwann cells has a growth supportive and differentiation-inducing effect on human NSCs.
To explore the differentiation fates of rat neural stem cells (NSCs) in different environmental conditions.
NSCs derived from 16-day-old rat embryo were proliferated in vitro and implanted into the ...brain of rats with intra-cerebral hemorrhage. At the same time some NSCs were co-cultured in vitro with Schwann cells derived from newborn rats. MAP-2, GFAP and GalC (which are the specific markers of neural cells, astrocytes and oligodendrocytes respectively), BrdU and beta-tubulin were detected by immunohistochemical and immunofluorescent methods.
BrdU positive cells that were implanted into the brain distributed around the hemorrhagic area. The majority of them were GFAP positive astrocytes while a few of them were beta-tubulin positive neural cells or GalC positive oligodendrocytes. After being co-cultured with Schwann cells in vitro, NSCs are predominately shown beta-tubulin and MAP-2 positive, and only a minority of them were GFAP or GalC positive.
The hemorrhagic environment in vivo induces NSCs to differentiate mainly into astrocytes while co-culture with Schwann cells in vitro induce the majority of NSCs to differentiate into neural cells.
Summary Transplantation of neural stem cells (NSC) has shown to elicit functional recovery in experimental animal and human models of neural disorders pertaining to cell loss or degeneration. ...However, the underlying mechanisms of the regimen are not well understood. The scenarios lead to the speculation of neuroregeneration and replacement of lost neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). The repair per se is extremely complex involving the re-building and modulation of synapses, neurites, neural cells and glial cells. Neurotrophins, which nourish the CNS and the PNS, may attribute to the functional improvement after neural stem cell transplantation. Recent studies suggested the CNS plasticity may be modulated by the class I major histocompatibility complex (MHC), which are in turn regulated by neurotrophins. Based upon these findings, we speculate that the neurotrophins derived from the transplanted NSC may modulate the expression of the major histocompatibility complex in the injured microenvironment to facilitate neurological recovery. The proposition may have clues on the development of novel treatment modality to cure CNS injury.
To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats.
Schwann cells originated from sciatic nerves of 1 to 2-day-old ...rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively.
BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43 expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas.
The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.
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