Ki-Suk Paik

Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury

Human bone marrow‐derived mesenchymal stem cells (hMSCs) are considered a desirable cell source for autologous cell transplantation therapy to treat nervous system injury due to their ability to differentiate into specific cell types and render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. To potentiate their possible trophic effect, hMSCs were induced without genetic modification to adopt characteristics of Schwann cells (SCs), which provide trophic support for regenerating axons. The induced hMSCs (shMSCs) adopted a SC‐like morphology and expressed SC‐specific proteins including the p75 neurotrophin receptor, which correlated with cell‐cycle exit. In addition, shMSCs secreted higher amounts of several growth factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) when compared with uninduced hMSCs. Coculture of shMSCs with Neuro2A cells significantly increased neurite outgrowth and cell proliferation but decreased cell death. Transplantation of shMSCs in an ex vivo model of spinal cord injury dramatically enhanced axonal outgrowth, which was mediated by HGF and VEGF secretion and also decreased cell death. These results demonstrate that shMSCs could serve as an endogenous source of neurotrophic growth factors to facilitate axonal regeneration while at the same time protecting the resident cells at the site of tissue injury. We propose that these induced hMSCs without genetic modification are useful for autologous cell therapy to treat nervous system injury.

Transplantation of mesenchymal stem cells enhances axonal outgrowth and cell survival in an organotypic spinal cord slice culture

Mesenchymal stem cells (MSCs) have demonstrated a measurable therapeutic effect following transplantation into animal models of spinal cord injury. However, the mechanism(s) by which transplanted cells promote nerve regeneration and/or functional recovery remains indeterminate. Several studies have suggested that MSCs promote tissue repair via secretion of trophic factors, but delineating the effect of such factors is difficult due to the complexity of the in vivo systems. Therefore, we developed an organotypic spinal cord slice culture system that can be sustained for sufficient periods of time in vitro to evaluate nerve regeneration as an ex vivo model of spinal cord injury. Using this model, we demonstrate that treatment of lumbar slices of spinal cord with lysolecithin induced a significant degree of cell death and demyelination of nerve fibers, but that these effects were ameliorated to a significant extent following co-culture of slices with human MSCs (hMSCs). The results indicate that transplanted hMSCs alter the tissue microenvironment in a way that promotes survival of endogenous cells, including injured neurons, immature oligodendrocytes and oligodendrocyte progenitor cells. This ex vivo culture system represents a useful tool to further dissect the mechanism(s) by which MSCs promote regeneration of injured nervous tissue.

Relationship between the curve of Spee and dentofacial morphology evaluated with a 3-dimensional reconstruction method in Korean adults

INTRODUCTION The purposes of this study were to examine the curve of Spee of the maxillary and mandibular arches by using a 3-dimensional reconstruction method and to determine the relationship between the curve of Spee and dentofacial morphology with multiple regression analysis. METHODS Lateral cephalograms and dental models were evaluated from 18 Korean men and 31 Korean women. The depth of the curve of Spee was measured on the virtual dental models with computer software. Seventeen cephalometric variables related to the lateral cephalograms were analyzed to determine differences in dentofacial morphology. The Pearson correlation analysis and a multiple linear regression analysis were performed to determine the relationship between the curve of Spee as the dependent variable and other cephalometric and dental variables as the independent variables. RESULTS The depth of the curve of Spee in the mandibular arch was significantly related to overbite, overjet, and the sagittal position of the mandible with respect to the anterior cranial base. The curve of Spee was not affected by sex. CONCLUSIONS These results will assist in the determination of the sagittal organization of the teeth as a reference for prosthetic restoration and orthodontic treatment.

The three-dimensional relationship on a virtual model between the maxillary anterior teeth and incisive papilla.

STATEMENT OF PROBLEM The incisive papilla as an anatomical landmark has historically been used to determine anterior incisal tooth position for complete denture prostheses. There are numerous data regarding its position, but 3-dimensional orthographic measurements are scarce. PURPOSE The purpose of this study was to evaluate the orthographic anteroposterior distance between the posterior border of the incisive papilla and a reference point or vector. MATERIAL AND METHODS Using a 3-dimensional laser scanner and reconstruction computer software, 9 measurements were made orthographically on an individually established reference plane. The following 3 measurements were made to determine the spatial relationship between the anterior tooth and the incisive papilla: IP, incisor to papilla, IIC, incisor to intercanine line, and ICP, intercanine line to papilla. In addition, the following 6 measurements were made to evaluate the correlation of the factors determining arch shape with the previously described 3 measurements: ICW, intercanine width, AL, arch length, AW, arch width, ICR, incisor to canine radius, ICA, incisor to canine angle, and IMA, incisor to molar angle. The correlation among all values was investigated. Descriptive statistics and an independent sample t test between genders was performed (alpha =.05). RESULTS The average IP distance (SD) was 11.96 (1.37) mm with no significant gender difference (P = .052). There were gender differences in IIC (P = .001), AL (P = .017), and ICA (P = .013). ICA had the largest negative or positive correlation coefficients with parameters related to the incisive papilla such as IP, IIC, and ICP. CONCLUSIONS The mean IP value obtained by 3-dimensional orthographic measurements was significantly larger than the classical data, however, it is impossible to make direct comparisons. The central incisor position of dentate subjects has a significant relationship with the ICA value which represents the premaxillary divergence.

Ankyrin repeat-rich membrane spanning/Kidins220 protein interacts with mammalian Septin 5

Neurotrophin receptors utilize specific adaptor proteins to activate signaling pathways involved in various neuronal functions, such as neurite outgrowth and cytoskeletal remodeling. The Ankyrin-Repeat Rich Membrane Spanning (ARMS)/kinase D-interacting substrate-220 kDa (Kidins220) serves as a unique downstream adaptor protein of Trk receptor tyrosine kinases. To gain insight into the role of ARMS/Kidins220, a yeast two-hybrid screen of a rat dorsal root ganglion library was performed using the C-terminal region of ARMS/Kidins220 as bait. The screen identified a mammalian septin, Septin 5 (Sept5), as an interacting protein. Co-immunoprecipitation using lysates from transiently transfected HEK-293 cells revealed the specific interaction between ARMS/Kidins220 and Sept5. Endogenous ARMS/Kidins220 and Sept5 proteins were colocalized in primary hippocampal neurons and were also predominantly expressed at the plasma membrane and in the tips of growing neurites in nerve growth factor-treated PC12 cells. Mapping of Sept5 domains important for ARMS/Kidins220 binding revealed a highly conserved N-terminal region of Sept5. The direct interaction between ARMS/Kidins220 and Sept5 suggests a possible role of ARMS/Kidins220 as a functional link between neurotrophin receptors and septins to mediate neurotrophin-induced intracellular signaling events, such as neurite outgrowth and cytoskeletal remodeling.

Corrigendum to “Transplantation of mesenchymal stem cells enhances axonal outgrowth and cell survival in an organotypic spinal cord slice culture” [Neurosci. Lett. 454 (1) (2009) 43–48]

Corrigendum to “Transplantation of mesenchymal stem cells enhances axonal outgrowth and cell survival in an organotypic spinal cord slice culture” [Neurosci. Lett. 454 (1) (2009) 43–48] Jung-Sun Choa, Hwan-Woo Parka, Sang-Kyu Parkb, Sangho Rohb, Soo-Kyung Kangc, Ki-Suk Paika, Mi-Sook Changa,∗ a Department of Oral Anatomy, Dental Research Institute & School of Dentistry, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea b Craniomaxillofacial Reconstructive Science Major, Dental Research Institute & School of Dentistry, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea c Department of Biotechnology, College of Veterinary Medicine, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-749, Republic of Korea