1.Fabrication Techniques of Nerve Guidance Conduits for Nerve Regeneration
Nae-Un KANG ; Seung-Jae LEE ; So-Jung GWAK
Yonsei Medical Journal 2022;63(2):114-123
Neuronal loss and axonal degeneration after spinal cord injury or peripheral injury result in the loss of sensory and motor functions. Nerve regeneration is a complicated and medical challenge that requires suitable guides to bridge nerve injury gaps and restore nerve function. Due to the hostility of the microenvironment in the lesion, multiple conditions should be fulfilled to achieve improved functional recovery. Many nerve conduits have been fabricated using various natural and synthetic polymers. The design and material of the nerve guide conduits were carefully reviewed. A detailed review was conducted on the fabrication method of the nerve guide conduit for nerve regeneration. The typical fabrication methods used to fabricate nerve conduits are dip coating, solvent casting, micropatterning, electrospinning, and additive manufacturing. The advantages and disadvantages of the fabrication methods were reported, and research to overcome these limitations was reviewed. Extensive reviews have focused on the biological functions and in vivo performance of polymeric nerve conduits. In this paper, we emphasize the fabrication method of nerve conduits by polymers and their properties. By learning from the existing candidates, we can advance the strategies for designing novel polymeric systems with better properties for nerve regeneration.
2.Combination Therapy by Tissue-Specific Suicide Gene and Bevacizumab in Intramedullary Spinal Cord Tumor
So-Jung GWAK ; Lihua CHE ; Yeomin YUN ; Minhyung LEE ; Yoon HA
Yonsei Medical Journal 2020;61(12):1042-1049
Purpose:
Malignant gliomas are aggressive spinal cord tumors. In this study, we hypothesized that combination therapy using an anti-angiogenic agent, bevacizumab, and hypoxia-inducible glioblastoma-specific suicide gene could reduce tumor growth.
Materials and Methods:
In the present study, we evaluated the effect of combination therapy using bevacizumab and pEpo-NI2-SV-TK in reducing the proliferation of C6 cells and tumor growth in the spinal cord. Spinal cord tumor was generated by the injection of C6 cells into the T5 level of the spinal cord. Complexes of branched polyethylenimine (bPEI)/pEpo-NI2-SV-TK were injected into the spinal cord tumor. Bevacizumab was then administered by an intraperitoneal injection at a dose of 7 mg/kg. The anti-cancer effects of combination therapy were analyzed by histological analyses and magnetic resonance imaging (MRI). The Basso, Beattie and Bresnahan scale scores for all of the treatment groups were recorded every other day for 15 days to assess the rat hindlimb strength.
Results:
The complexes of bPEI/pEpo-NI2-SV-TK inhibited the viability of C6 cells in the hypoxia condition at 5 days after treatment with ganciclovir. Bevacizumab was decreased in the cell viability of human umbilical vein endothelial cells. Combination therapy reduced the tumor size by histological analyses and MRI. The combination therapy group showed improved hind-limb function compared to the other groups that were administered pEpo-NI2-SV-TK alone or bevacizumab alone.
Conclusion
This study suggests that combination therapy using bevacizumab with the pEpo-NI2-SV-TK therapeutic gene could be useful for increasing its therapeutic benefits for intramedullary spinal cord tumors.
3.Regeneration of kidney tissue using in vitro cultured fetal kidney cells.
Sang Soo KIM ; So Jung GWAK ; Joungho HAN ; Moon Hyang PARK ; Kang Won SONG ; Byung Soo KIM
Experimental & Molecular Medicine 2008;40(4):361-369
Transplanting fetal kidney cells (FKCs) can regenerate kidney. This requires in vitro expansion in cell number to acquire enough cells for transplantation. However, FKCs may change their cellular characteristics during expansion and, thus, may not regenerate kidney tissue upon transplantation. We investigated how cell culture period affects cellular characteristics and in vivo regenerative potential of FKCs. As the passage number increased, cell growth rate and colony forming ability decreased while senescence and apoptosis increased. To examine in vivo regenerative potential, FKCs cultured through different numbers of passages were implanted into the parenchyma of kidneys of immunodeficient mice using fibrin gel for 4 wk. Histological analyses showed passage-dependent kidney tissue regeneration, and the regeneration was better when cells from lower number of passages were implanted. This result shows that in vitro culture of FKCs significantly affects the cell characteristics and in vivo tissue regenerative potential.
Animals
;
Apoptosis/physiology
;
Cell Aging/physiology
;
Cell Culture Techniques
;
Cell Proliferation
;
Cells, Cultured
;
Colony-Forming Units Assay
;
Female
;
Fetal Tissue Transplantation/methods/physiology
;
Fetus/cytology/*physiology
;
Kidney/embryology/*physiology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Nude
;
Rats
;
Rats, Sprague-Dawley
;
Regeneration/*physiology
4.Hepatocyte Transplantation Using Fibrin Gel.
Dongho CHOI ; So Jung GWAK ; Hanjoon KIM ; Kyeong Geun LEE ; Seung Sam PAIK ; Doo Jin PAIK ; Hwon Kyum PARK ; Oh Jung KWON ; Byung Soo KIM ; Kwang Soo LEE
The Journal of the Korean Society for Transplantation 2003;17(1):20-25
PURPOSE: Whole liver transplantation, an effective therapy for many inherited and acquired hepatic disorders, has limitations including donor shortage and fatal surgical complications. Hepatocyte transplantation, which is simpler and less expensive than whole liver transplantation, allows the use of living related donors, permits the use of a single donor organ for multiple recipients, and makes possible the cryopreservation of hepatocytes for future use. However, choosing a proper scaffold for hepatocyte transplantation hampers wide use of hepatocyte transplantation. We performed hepatocyte transplantation using fibrin gel, as a cell transplantation scaffold and evaluated their effectiveness. METHODS: Female, five week old FVB mice, were prepared for donors, and two male, five week old nude mice, were used as recipients. Liver cells were isolated from FVB donors. The cell viability exceeded 95% as assessed by the trypan blue exclusion method. For three nude mice, 5x10(6) cells resuspended in 500microliter of fibrinogen were mixed with 500microliter thrombin, and were injected into the peritoneal cavity of each mouse. One nude mouse was transplanted with 5x10(6) cells resuspended in 500 microliter medium, which served as a negative control. Specimens were retrieved at one week, and histological and immunohistochemical analyses wereperformed. RESULTS: In the negative control, all transplanted hepatocytes disappeared at one week. In mice transplanted both fibrin gel and hepatocytes, conglomerates containing hepatocytes were observed on the intestinal mesentery. The hepatocytes were identified by H & E staining and immunohistochemistry using anti-hepatocyte antibody. Functional activity was evaluated with PAS staining. CONCLUSION: In this preliminary study, stable hepatocyte engraftment was achieved in hepatocyte transplantation with fibrin gel, but not in hepatocyte transplantation without scaffold. More studies on comparison between fibrin gel and injectable scaffolds would be necessary. Improvement on both initial vascularization and proliferation of transplanted hepatocytes is a target of our future work.
Animals
;
Cell Survival
;
Cell Transplantation
;
Cryopreservation
;
Female
;
Fibrin*
;
Fibrinogen
;
Hepatocytes*
;
Humans
;
Immunohistochemistry
;
Liver
;
Liver Transplantation
;
Male
;
Mesentery
;
Mice
;
Mice, Nude
;
Peritoneal Cavity
;
Thrombin
;
Tissue Donors
;
Transplants
;
Trypan Blue
5.Role of MRI in Diagnostic Evaluation of Papillary Lesions of the Breast.
So Mi LEE ; Hye Jung KIM ; Yeon Joo GWAK ; Hui Joong LEE ; Yun Jin JANG ; Kyung Min SHIN ; Ji Young PARK ; Jin Hyang JUNG
Journal of the Korean Society of Magnetic Resonance in Medicine 2010;14(1):41-46
PURPOSE: To evaluate the role of magnetic resonance imaging (MRI) in the diagnosis of papillary lesions of the breast. MATERIALS AND METHODS: Among 45 papillary lesions diagnosed at ultrasonography-guided core biopsy (USCB), 27 benign papillary lesions in 22 patients who underwent breast MRI were reviewed. The excsional biopsy was performed in 1-10 days after MRI was done. In MRI findings, lesions were considered suspicious if they show irregular, rim enhancement, or linear enhancement in morphologic evaluation, or washout enhancement pattern of delayed phase in dynamic enhancement characteristics. Diffusion-weighted images were analyzed according to visibility of lesions. MRI findings were correlated with pathologic results at excisional biopsy. RESULTS: At excisional biopsy, two lesions (9%) were diagnosed malignant in 22 benign papillary lesions without atypia by USCB and 4 (80%) were malignant in 5 benign papillary lesions with atypia by USCB. Among 18 lesions detected on MRI, 16 lesions showed suspicious findings on MRI, 11 lesions (69%) were diagnosed as benign and 5 (31%) were malignant. Among 12 lesions detected on diffusion weighted imaging, 10 lesions were diagnosed as benign and 2 were malignant. MRI findings were not significantly correlated with pathologic results at excisional biopsy. CONCLUSION: MRI findings were not useful to predict malignancy in benign papillary lesions diagnosed at USCB, because MRI findings of these were mostly suspicious (88.9%, 16/18). The benign papillary lesion should be included in the false positive lesion on breast MRI.
Biopsy
;
Breast
;
Breast Neoplasms
;
Diffusion
;
Humans
;
Magnetic Resonance Imaging
6.Role of MRI in Diagnostic Evaluation of Papillary Lesions of the Breast.
So Mi LEE ; Hye Jung KIM ; Yeon Joo GWAK ; Hui Joong LEE ; Yun Jin JANG ; Kyung Min SHIN ; Ji Young PARK ; Jin Hyang JUNG
Journal of the Korean Society of Magnetic Resonance in Medicine 2010;14(1):41-46
PURPOSE: To evaluate the role of magnetic resonance imaging (MRI) in the diagnosis of papillary lesions of the breast. MATERIALS AND METHODS: Among 45 papillary lesions diagnosed at ultrasonography-guided core biopsy (USCB), 27 benign papillary lesions in 22 patients who underwent breast MRI were reviewed. The excsional biopsy was performed in 1-10 days after MRI was done. In MRI findings, lesions were considered suspicious if they show irregular, rim enhancement, or linear enhancement in morphologic evaluation, or washout enhancement pattern of delayed phase in dynamic enhancement characteristics. Diffusion-weighted images were analyzed according to visibility of lesions. MRI findings were correlated with pathologic results at excisional biopsy. RESULTS: At excisional biopsy, two lesions (9%) were diagnosed malignant in 22 benign papillary lesions without atypia by USCB and 4 (80%) were malignant in 5 benign papillary lesions with atypia by USCB. Among 18 lesions detected on MRI, 16 lesions showed suspicious findings on MRI, 11 lesions (69%) were diagnosed as benign and 5 (31%) were malignant. Among 12 lesions detected on diffusion weighted imaging, 10 lesions were diagnosed as benign and 2 were malignant. MRI findings were not significantly correlated with pathologic results at excisional biopsy. CONCLUSION: MRI findings were not useful to predict malignancy in benign papillary lesions diagnosed at USCB, because MRI findings of these were mostly suspicious (88.9%, 16/18). The benign papillary lesion should be included in the false positive lesion on breast MRI.
Biopsy
;
Breast
;
Breast Neoplasms
;
Diffusion
;
Humans
;
Magnetic Resonance Imaging
7.Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells.
Sang Soo KIM ; Sang Hyun LIM ; Seung Woo CHO ; So Jung GWAK ; Yoo Sun HONG ; Byung Chul CHANG ; Moon Hyang PARK ; Kang Won SONG ; Cha Yong CHOI ; Byung Soo KIM
Experimental & Molecular Medicine 2006;38(3):273-283
To increase the biocompatibility and durability of glutaraldehyde (GA)-fixed valves, a biological coating with viable endothelial cells (ECs) has been proposed. However, stable EC layers have not been formed successfully on GA-fixed valves due to their inability to repopulate. In this study, to improve cellular adhesion and proliferation, the GA-fixed prostheses were detoxified by treatment with citric acid to remove free aldehyde groups. Canine bone marrow mononuclear cells (MNCs) were differentiated into EC-like cells and myofibroblast-like cells in vitro. Detoxified prostheses were seeded and recellularized with differentiated bone marrow-derived cells (BMCs) for seven days. Untreated GA-fixed prostheses were used as controls. Cell attachment, proliferation, metabolic activity, and viability were investigated and cell-seeded leaflets were histologically analyzed. On detoxified GA-fixed prostheses, BMC seeding resulted in uninhibited cell proliferation after seven days. In contrast, on untreated GA-fixed prostheses, cell attachment was poor and no viable cells were observed. Positive staining for smooth muscle a-actin, CD31, and proliferating cell nuclear antigen was observed on the luminal side of the detoxified valve leaflets, indicating differentiation and proliferation of the seeded BMCs. These results demonstrate that the treatment of GA-fixed valves with citric acid established a surface more suitable for cellular attachment and proliferation. Engineering heart valves by seeding detoxified GA-fixed biological valve prostheses with BMCs may increase biocompatibility and durability of the prostheses. This method could be utilized as a new approach for the restoration of heart valve structure and function in the treatment of end-stage heart valve disease.
Tissue Fixation
;
Tissue Engineering/*methods
;
Swine
;
Proliferating Cell Nuclear Antigen/analysis
;
Muscle, Smooth/chemistry
;
Microscopy, Electron, Scanning
;
Immunohistochemistry
;
Heart Valves/cytology/*physiology
;
Heart Valve Prosthesis
;
Glutaral/*chemistry
;
Endothelial Cells/cytology/physiology
;
Dogs
;
Cell Survival/physiology
;
Cell Proliferation
;
Cell Differentiation/physiology
;
Cell Culture Techniques/*methods
;
Cell Adhesion/physiology
;
Bone Marrow Cells/chemistry/*physiology/ultrastructure
;
Antigens, CD31/analysis
;
Animals
;
Actins/analysis