Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells a...Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.展开更多
Biodegradable hydrogels are promising biomaterials for use in controlled-release systems for skin tissue regeneration. Controlled delivery systems constitute an important aspect of tissue engineering because they can ...Biodegradable hydrogels are promising biomaterials for use in controlled-release systems for skin tissue regeneration. Controlled delivery systems constitute an important aspect of tissue engineering because they can modulate various physiological responses, including early immune response, tissue remodeling, and cell proliferation and maturation in the wound-healing process. Hydrogels composed of various biomaterials have been developed to overcome the limitations of conventional drug- or protein-delivery systems, such as limited targeting ability, low stability, and the induction of drug resistance. Hydrogels based on keratin, a natural polymer extracted from human hair, can provide adequate cell support and control homeostasis. Consequently, they can be applied for skin tissue engineering. In this study, we prepared degradable, tunable, and biocompatible hydrogels for controllable protein delivery. We synthesized keratin-fibrinogen (KER-FBG) by the chemical coupling reaction and prepared hydrogels through polymerization with thrombin. The structures and morphologies of the KER-FBG hydrogels were confirmed. Furthermore, the mechanical properties, swelling ratio, degradation, release behavior, and biocompatibility were investigated. The KER-FBG hydrogels presented promising biological performance, indicating that the material is suitable as a controlled protein delivery carrier.展开更多
基金supported by a"KRCF National Agenda Project",by an Asan Life Science Institute Grant(12-241)from the Asan Medical Center,Seoul,Korea
文摘Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(NRF-2020R1A2C2011937,2020R1C1C1007129)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare(HI22C1572)R&BD Program through the INNOPOLIS funded by Ministry of Science and ICT(2021-IT-RD-0059-01-101).
文摘Biodegradable hydrogels are promising biomaterials for use in controlled-release systems for skin tissue regeneration. Controlled delivery systems constitute an important aspect of tissue engineering because they can modulate various physiological responses, including early immune response, tissue remodeling, and cell proliferation and maturation in the wound-healing process. Hydrogels composed of various biomaterials have been developed to overcome the limitations of conventional drug- or protein-delivery systems, such as limited targeting ability, low stability, and the induction of drug resistance. Hydrogels based on keratin, a natural polymer extracted from human hair, can provide adequate cell support and control homeostasis. Consequently, they can be applied for skin tissue engineering. In this study, we prepared degradable, tunable, and biocompatible hydrogels for controllable protein delivery. We synthesized keratin-fibrinogen (KER-FBG) by the chemical coupling reaction and prepared hydrogels through polymerization with thrombin. The structures and morphologies of the KER-FBG hydrogels were confirmed. Furthermore, the mechanical properties, swelling ratio, degradation, release behavior, and biocompatibility were investigated. The KER-FBG hydrogels presented promising biological performance, indicating that the material is suitable as a controlled protein delivery carrier.