Using Three-Dimensional Printing to Create Individualized Cranial Nerve Models for Skull Base Tumor Surgery.

OBJECTIVE: Using three-dimensional (3D) printing to create individualized patient models of the skull base, the optic chiasm and facial nerve can be previsualized to help identify and protect these structures during tumor removal surgery. METHODS: Preoperative imaging data for 2 cases of sellar tumor and 1 case of acoustic neuroma were obtained. Based on these data, the cranial nerves were visualized using 3D T1-weighted turbo field echo sequence and diffusion tensor imaging-based fiber tracking. Mimics software was used to create 3D reconstructions of the skull base regions surrounding the tumors, and 3D solid models were printed for use in simulation of the basic surgical steps. RESULTS: The 3D printed personalized skull base tumor solid models contained information regarding the skull, brain tissue, blood vessels, cranial nerves, tumors, and other associated structures. The sphenoid sinus anatomy, saddle area, and cerebellopontine angle region could be visually displayed, and the spatial relationship between the tumor and the cranial nerves and important blood vessels was clearly defined. The models allowed for simulation of the operation, prediction of operative details, and verification of accuracy of cranial nerve reconstruction during the operation. Questionnaire assessment showed that neurosurgeons highly valued the accuracy and usefulness of these skull base tumor models. CONCLUSIONS: 3D printed models of skull base tumors and nearby cranial nerves, by allowing for the surgical procedure to be simulated beforehand, facilitate preoperative planning and help prevent cranial nerve injury.

Transplantation of adipocyte-derived stem cells in a hydrogel scaffold for the repair of cortical contusion injury in rats.

Adipocyte-derived stem cells have emerged as a novel source of stem cell therapy for their autologous and readily accessible and pluripotent potential to differentiate into different lineages such as neural stem cells (NSCs) and endothelial progenitor cells (EPCs). Transplantation of NSCs and EPCs has been promising for the repair of brain injury. We explored using co-transplanted hydrogel scaffold to improve the survival of the transplanted cells and recovery of neurological function. Adult Wistar rats were transplanted with EPC-hydrogel, NSC-hydrogel, NSC-EPC-hydrogel, EPC only, or NSC only 7 days after cortical contusion injury. Behavioral tests were performed to evaluate neurological function before, and 1, 2, 3, and 4 weeks after transplantation. Size of injury, extent of vascularization, as well as the survival and differentiation of the transplanted EPCs and NSCs, were evaluated at week 5. All transplantation groups displayed significantly better neurological function compared with the control groups. Improved neurological function correlated with significantly smaller injury volumes than that of the saline group. Using immunostaining, we have shown that while transplanted NSCs differentiated into both neurons and astrocytes, the EPCs were incorporated into vessel epithelia. The extent of reactive gliosis (based on glial fibrillary acidic protein immunostaining) was significantly reduced in all treatment groups (NSC-EPC-hydrogel, NSC-hydrogel, and EPC-hydrogel) when compared with the saline group, with the highest reduction in the NSC-EPC-hydrogel transplantation group. Thus, co-transplantation of hydrogel scaffold provides a more conducive environment for the survival and differentiation of NSCs and EPCs at the site of brain injury, leading to improved vascularization and better recovery of neurological function.

Krüppel-like factor 9 inhibits glioma cell proliferation and tumorigenicity via downregulation of miR-21.

Krüppel-like factors (KLFs) are zinc finger-containing transcription factors that play key roles in the regulation of differentiation and development as well as biological processes central to the development of malignancies. Increasing evidence indicates that Krüppel-like factor 9 (KLF9) plays a critical role in regulating tumorigenesis. However, the biological role and molecular mechanism of KLF9 in glioma progression remain unclear. Herein, we found that KLF9 expression was strongly reduced in gliomas. Reduced KLF9 expression promoted glioma cell proliferation. Importantly, re-constitution of KLF9 expression inhibited glioma cell proliferation and tumor growth in vivo. Furthermore, we determined that KLF9 interacted with the miR-21 promoter, leading to suppression of miR-21 expression and cell cycle arrest. Taken together, our findings indicate a novel mechanism for KLF function in tumorigenesis and may also suggest new targets for clinical intervention in human cancer.

[Differentiation of prostate cancer from benign prostatic disease by total prostate specific antigen dynamic profiles after transrectal prostate biopsy].

OBJECTIVE: To investigate the possibility of differentiating prostate cancer (PCa) from benign prostatic disease by total prostate specific antigen (T-PSA) dynamic profiles following transrectal prostate biopsy, and to determine the cutoff value of the T-PSA ratio between pre- and post-biopsy. METHODS: A total of 36 men at the mean age of 69.89 years with increased serum PSA underwent prostate biopsy guided by transrectal ultrasound, followed by measurement of T-PSA at 10, 30, 60 and 90 min, plotting of T-PSA dynamic profiles and calculation of the pre- and post-biopsy T-PSA ratio at different time points. The patients were divided into a PCa and a non-PCa group according to the pathological results and compared for the difference in T-PSA ratios. The cutoff value of the pre- and post-biopsy T-PSA ratio was determined for the differentiation of PCa from benign prostatic diseases. RESULTS: The post-biopsy T-PSA ratio was obviously higher in the non-PCa than in the PCa group (P < 0.05). With the ROC curve applied, the cutoff value of the T-PSA ratio was 1.5 and the best time for blood sampling was 30 minutes after the biopsy, with a 75% sensitivity and a 93% specificity. CONCLUSION: Evaluation of the T-PSA ratio 30 minutes after biopsy might help screen the high-risk PCa population. Biopsy should be repeated for those with a lower T-PSA ratio in spite of initial benign results. The results are to be further supported by more prospective studies.

[Effect of superparamagnetic iron oxide labeling on neural stem cell survival and proliferation].

OBJECTIVE: To study the effect of superparamgnetic iron oxides (ferumoxides) on the survival and proliferation of neural stem cells (NSCs) and determine the optimal ferumoxides concentration for labeling. METHODS: Bone marrow stromal cells (BMSCs) were obtained from rat femoral marrow and cultured in vitro to induce their differentiation into NSCs. Ferumoxides labeling of the NSCs was performed with different final concentrations of ferumoxides, and the labeling efficiency and viability of the labeled NSCs were evaluated by Prussian blue staining, MTT assay, flow cytometry and transmission electron microscope. RESULTS: The NSCs could be effectively labeled with ferumoxides with a labeling efficiency of around 90%. Prussian blue staining showed numerous fine granules with blue staining in the cytoplasm of the labeled NSCs, and the intensity of the blue staining was in positive correlation with the ferumoxide concentration for labeling. Transmission electron microscopy of the labeled NSCs revealed the presence of numerous vesicles spreading in the cytoplasm and filled with electron-dense magnetic iron particles. The ferumoxides vesicles increased with the labeling concentration of ferumoxides, and at the final concentration exceeding 25 microg/ml, ferumoxides vesicles in the NSCs gave rise to conglomeration which hampered observation of the cellular ultrastructure by transmission electron microscope. The results of flow cytometry and MTT assay demonstrated that the cell viability, proliferation, differentiation and apoptosis of the labeled cells were affected by ferumoxides at the concentration above 25 microg/ml, but such effects could be minimal at lower concentrations. CONCLUSION: Ferumoxides might be feasible for in vitro labeling of the NSCs with the optimal concentration of 25 microg/ml.

In vitro culture and induced differentiation of adult rat neural stem cells from the corpus striatum.

OBJECTIVE: To investigate the in vitro multipotential differentiation of neural stem cells from adult rat corpus striatum. METHODS: The neural stem cells isolated from adult rat corpus striatum were cultured in serum-free medium to obtain cell suspension before monoclonal subculturing and differential induction. Immunocytochemical staining and reverse transcriptional PCR (RT-PCR) were performed to identify the properties of the differentiated cells. RESULTS: Numerous cell clusters were formed in the phase of monoclonal culture, and different types of cells were observed 3 d after induction with fetal bovine serum. The differentiated cells contained cells positive for nestin, neuron-specific enolase (NSE) positive cells, and glial fibrillary acidic protein (GFAP) positive cells. RT-PCR identified expressions of the transcripts for neural cell-associated genes including brain factor-1, gamma-aminobutyric acid alpha-receptor gamma-subunit, tyrosine hydroxylase and tryptophan hydroxylase. CONCLUSION: The cells separated from adult rat corpus striatum possess the ability of self-proliferation and multipotential differentiation, and are identified as the stem cells of the central nervous system.