Trabecular structural difference between the superior and inferior regions of the vertebral body: a cadaveric and clinical study.

Background: Osteoporotic vertebral compression fractures commonly involve the superior vertebral body; however, their associated causes have not yet been clearly established. This study aimed to determine the trabecular structural differences between the superior and inferior regions of the vertebral body using cadaveric and clinical studies. Materials and methods: First, five vertebrae were collected from three human cadavers. The trabecular structures of the superior and inferior regions of each vertebral body were analyzed using micro-computed tomography (micro-CT), finite element analysis (FEA), and biomechanical test. Based on the results of the ex vivo study, we conducted a clinical study. Second, spine CT images were retrospectively collected. Bone volume and Hounsfield unit were analyzed for 192 vertebral bodies. Finally, after sample size calculation based on the pilot study, prospectively, 200 participants underwent dual-energy X-ray absorptiometry (DXA) of the lateral spine. The bone mineral densities (BMDs) of the superior and inferior regions of each lumbar vertebral body were measured. The paired t-test and Wilcoxon signed-rank test were used for the statistical analyses, and p-value < 0.05 was considered significant. Results: Cadaver studies revealed differences between the superior and inferior trabecular bone structures. The bone volume ratio, BMD, and various other trabecular parameters advocated for decreased strength of the superior region. Throughout the biomechanical study, the limitations of the compression force were 3.44 and 4.63 N/m2 for the superior and inferior regions, respectively. In the FEA study, the inferior region had a lower average displacement and higher von Mises stress than the superior region. In the clinical spine CT-based bone volume and BMD study, the bone volume was significantly higher in the inferior region than in the superior region. In the lateral spine DXA, the mean BMD of the superior region of vertebral bodies was significantly lower compared with that of the inferior region. Conclusion: The superior trabecular structure of the lumbar vertebral bodies possesses more biomechanical susceptibility compared with the inferior trabecular structure, confirming its dominant role in causing osteoporotic vertebral fractures. Physicians should also focus on the BMD values of the superior region of the vertebral body using lateral spine DXA to evaluate osteoporosis.

Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture.

Organoids, a multi-cellular and organ-like structure cultured in vitro, can be used in a variety of fields such as disease modeling, drug discovery, or cell therapy development. When organoids derived from Lgr5 stem cells are cultured ex vivo, recombinant R-spondin-1 protein should be added at a high concentration for the initiation and maintenance of the organoids. Because the addition of large amounts of R-spondin-1 greatly increases the cost of organoids, the organoids grown with R-spondin-1 are not practical for large-scale drug screening and for the development of therapeutic agents. In this study, we tried to find a R-spondin-1 substitute compound that is able initiate small intestinal organoids without the use of the R-spondin-1 protein; thus, using organoid media that each included one compound from among an 8,364 compound library instead of R-spondin-1, we observed whether organoids were established from the crypts of the small intestine. As a result, we found one compound that could promote the initial formation and growth of enteroids in the medium without R-spondin-1 and named it RS-246204. The enteroids grown with RS-246204 had a similar differentiation capacity as well as self-renewal capacity as the enteroids grown with R-spondin-1. Furthermore, the RS-246204-derived enteroids could successfully produce the forskolin induced swelling and the organoid based epithelial to mesenchymal transition model. This compound could be used for developing a cost-efficient culturing method for intestinal organoids as well as for exploring Lgr5 signaling, intestinal stem cell physiology and therapeutics for GI tract diseases.

Therapeutic effect of BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) in a rodent model of middle cerebral artery occlusion.

Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) represents the major type of stroke; however, there are still very limited therapeutic options for the stroke-damaged patients. In this study, we evaluated the neurogenic and therapeutic potentials of human neural stem cells (NSCs) overexpressing brain-derived neurotrophic factor (HB1.F3.BDNF) following transplantation into a rodent model of MCAo. F3.BDNF human NSCs (F3.BDNF) were transplanted into the contralateral side of striatum at 7 days after MCAo, and the transplanted animals were monitored up to 8 weeks using animal MRI and various behavioral tests before they were sacrificed for immunohistochemical analysis. Interestingly, animal MRI results indicate that the majority of contralaterally transplanted neural stem cells were migrated to the peri-infarct area, showing a pathotropism. Transplanted animals exhibited significant behavioral improvements in stepping, rotarod, and modified neurological severity score (mNSS) tests. We also found that the transplanted human cells were colocalized with nestin, DCX, MAP2, DARPP-32, TH, GAD65/67-positive cells, of which results can be correlated with neural regeneration and behavioral recovery in the transplanted animals. More importantly, we were able to detect high levels of human BDNF protein expression, presumably derived from the transplanted F3.BDNF. Taken together, these results provide strong evidence that human neural stem cells (F3.BDNF) are effective in treating stroke animal models.

Surface mapping of motor points in biceps brachii muscle.

OBJECTIVE: To localize the site of motor points within human biceps brachii muscles through surface mapping using electrophysiological method. METHOD: We recorded the compound muscle action potentials of each lattice of the biceps brachii in 40 healthy subjects. Standardized reference lines were made as the following: 1) a horizontal reference line (elbow crease) and 2) a vertical reference line connecting coracoid process and mid-point of the horizontal reference line. The Compound muscle action potentials were mapped in reference to the standardized reference lines. The locations of motor points were mapped to the skin surface, in the ratio to the length of the vertical and the half of the horizontal reference lines. RESULTS: The motor point of the short head of biceps was located at 69.0±4.9% distal and 19.1±9.5% medial to the mid-point of horizontal reference line. The location of the motor point of the long head of the biceps was 67.3±4.3% distal and 21.4±8.7% lateral. The motor point of the short head of the biceps was located more medially and distally in the male subjects compared to that in the female (p<0.05). CONCLUSION: This study showed electrophysiological motor points of the biceps brachii muscles through surface mapping. This data might improve the clinical efficacy and the feasibility of motor point targeting, when injecting botulinum neurotoxin in biceps brachii.

Proteomic identification of RREB1, PDE6B, and CD209 up-regulated in primitive gut tube differentiated from human embryonic stem cells.

OBJECTIVES: This study aimed to identify proteins important for the primitive gut tube differentiation from human embryonic stem cells (hESCs) by derivation method for pancreatic cells. METHODS: Proteins with altered expression levels in the process of differentiating to primitive gut tube from definitive endoderm of hESCs were investigated by comparative proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometric analyses. RESULTS: Differentiation to primitive gut tube from hESCs was analyzed using differentiation marker genes and proteins. Twenty-seven protein spots with significant changes in intensity were found by 2-dimensional gel electrophoresis, and 24 proteins were further identified. These proteins were functionally annotated based on gene ontology. The expression levels of 3 proteins, RREB1, PDE6B, and CD209, involved in signal transduction, were validated using quantitative reverse transcription-polymerase chain reaction and Western blot. Their mRNA and protein expression levels increased in primitive gut tube but not in definitive endoderm or embryonic body. CONCLUSIONS: The increase in expression of RREB1, PDE6B, and CD209 suggests that these proteins might play important roles in the differentiation of primitive gut tube cells from hESCs and in human primitive gut tube development into pancreas. Therefore, they could be developed as differentiation markers for identifying primitive gut tube cells.

In vivo Tracking of Human Neural Stem Cells Following Transplantation into a Rodent Model of Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Ischemic stroke caused by middle cerebral artery occlusion (MCAo) is the major type of stroke, but there are currently very limited options for cure. It has been shown that neural stem cells (NSCs) or neural precursor cells (NPCs) can survive and improve neurological deficits when they are engrafted in animal models of various neurological diseases. However, how the transplanted NSCs or NPCs are act in vivo in the injured or diseased brain is largely unknown. In this study, we utilized magnetic resonance imaging (MRI) techniques in order to understand the fates of human NSCs (HB1.F3) following transplantation into a rodent model of MCAo. METHODS AND RESULTS: HB1.F3 human NSCs were pre-labeled with ferumoxides (Feridex(®))-protamine sulfate complexes, which were visualized and examined by MRI up to 9 weeks after transplantation. Migration of the transplanted cells to the infarct area was further confirmed by histological methods. CONCLUSIONS: Based on these observations, we speculate that the transplanted NSCs have the extensive migratory ability to the injured site, which will in turn contribute to functional recovery in stroke.

In vivo tracking of human mesenchymal stem cells in experimental stroke.

To understand the fates of human mesenchymal stem cells (hMSCs) following transplantation into a rodent model of middle cerebral artery occlusion (MCAo), magnetic resonance imaging (MRI) techniques were employed, hMSCs were labeled with ferumoxides (Feridex)--protamine sulfate complexes, which were visualized and examined by MRI up to 10 weeks following transplantation. Migration of the transplanted cells to the infarcted area was further confirmed by histological methods. We found that the hMSCs transplanted in MCAo models possess the capacity to migrate to the infarcted area extensively in both ipsilateral and contralateral injections, exhibiting a pathotropism. We also analyzed the detailed migration patterns of transplanted hMSCs. We speculate that the extensive migratory ability of hMSCs may represent a therapeutic potential for developing efficient cell transplantation strategies in stroke.

Human embryonic stem cell-derived neural precursor transplants attenuate apomorphine-induced rotational behavior in rats with unilateral quinolinic acid lesions.

To test the efficacy of human embryonic stem cell (hESC)-derived neural precursors in an experimental model of Huntington's disease (HD), we differentiated hESC into nestin-positive neural precursors by co-culturing with PA6 stromal cells, and subsequently transplanted them into the striatum of quinolinic acid (QA)-induced HD model. The transplanted animals exhibited a behavioral recovery in the apomorphine-induced rotation test for 3 weeks after transplantation. The transplanted hESC-derived neural precursors were found in both cortex and striatum. They also exhibited some evidence of neuronal differentiation. At the time of examination, no tumor was detected. These results strongly suggest that hESC-derived neural precursors can lead to a behavioral recovery, as well as neuronal differentiation, in the pre-clinical model of HD.

In Vivo Tracking of Human Mesenchymal Stem Cells in Experimental Stroke.

To understand the fates of human mesenchymal stem cells (hMSCs) following transplantation into a rodent model of middle cerebral artery occlusion (MCAo), magnetic resonance imaging (MRI) techniques were employed. hMSCs were labeled with ferumoxides (Feridex®)-protamine sulfate complexes, which were visualized and examined by MRI up to 10 weeks following transplantation. Migration of the transplanted cells to the infarcted area was further confirmed by histological methods. We found that the hMSCs transplanted in MCAo models possess the capacity to migrate to the infarcted area extensively in both ipsilateral and contralateral injections, exhibiting a pathotropism. We also analyzed the detailed migration patterns of transplanted hMSCs. We speculate that the extensive migratory ability of hMSCs may represent a therapeutic potential for developing efficient cell transplantation strategies in stroke.

Morphometry of the nasal bones and piriform apertures in Koreans.

In order to understand the morphological characteristics of Korean noses, the nasal bones and piriform apertures were measured and classified in the dried skulls of Korean adults. The shapes of the nasal bones were classified into five types (Type A-E). Among the types of the nasal bone, Type A, in which the nasomaxillary sutures initially descended vertically and then obliquely, was present in 43.2% and Type B, in which the nasomaxillary sutures were concave in the middle part, was present in 52.3% of the noses examined. The height of the nasal bone was 25.9 +/- 3.8 mm in males, 24.5 +/- 3.7 mm in females; the width was 9.2 +/- 2.4 mm in males, 8.8 +/- 2.6 mm in females. The height of the piriform aperture was 30.1 +/- 2.6 mm in males, 28.0 +/- 2.8 mm in females; the upper width was 16.8+2.6 mm in males, 17.0 +/- 2.0 mm in females; the lower width was 25.7 +/- 1.7 mm in males, 25.4 +/- 2.1 mm in females. Each measurement was compared with those carried out in other populations.

Morphometrical changes of the human uterine tubes according to aging and menstrual cycle.

Studies on the morphological changes in the human uterine tube according to aging and menstrual cycle so far have been limited to microscopic aspects such as cellular changes, mainly due to the inaccessibility of specimens. In this study, postmortem analysis using both macroscopic and microscopic methods was performed using 55 human uterine tubes. The numbers and the degrees of convolution, and the length of the uterine tube had a tendency to decrease according to the increase of age in women by fifties. Under the influence of menopause, the total areas of the tube, mucosal layer and lumen in the ampulla, and lumen in the isthmus and infundibulum were shown to decrease on cross section. However, in the isthmus and infundibulum, the cross sectional area of the tube and mucosal layer did not show statistically significant changes. In the women at reproductive stages, the cross sectional areas of the tube, mucosa and lumen showed variations among different individuals, which may be due to the influence of menstrual cycle rather than the increase of age. No venous engorgement of the tubes was observed at the early proliferative, the mid-secretory and the postmenopausal stage. By contrast, full engorgement was observed at the early secretory stage and the menstrual stage.

Morphometry of nasal bases and nostrils in Koreans.

To investigate morphological characteristics of Korean noses, nasal bases and nostrils were measured and classified in Korean adults. The height and the width of the nasal base, the height and the width of the columella, the length of the long and short nostril axes, and nasal alar angle were measured. The shapes of the nostrils were classified into 7 types by the angle between the right and left long axes of the nostrils. Each measurement was compared with other studies.