http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Stem Cell Biology of the Central Nervous System
Okano, Hideyuki 한림대학교 환경·생명과학연구소 2003 [일송 국제심포지엄] 노화와 만성퇴행성 신경질환 Vol.- No.5
Neural stem cells (NSCs) are multipotential progenitor cells that have self-renewal activities. A single NSC is capable of generating various kinds of cells within the central nervous system (CNS), including neurons, astrocytes, and oligodendrocytes. Because of these characteristics, there is increasing interest in NSCs and neural progenitor cell from the aspects of both basic developmental biology and therapeutic applications to the damaged brain. This special issue, dedicated to understanding the nature of the NSCs present in the CNS, presents an introduction to several avenues of research that may lead to feasible strategies for manipulating cells in situ to treat the damaged brain. The topics covered by these studies include the extracellular factors and signal transduction cascades involved in the differentiation and maintenance of NSCs, the population dynamics and locations of NSCs in embryonic and adult brains, prospective identification and isolation of NSCs, the induction of NSCs to adopt particular neuronal phenotypes, and their transplantation into the damaged CNS.
Transaplantation of neural stem cells into the spinal cord after injury
Okano, Hideyuki,Ogawa, Yuto,Nakamura, Masaya,Kaneko, Shinjiro,Iwanami, Akio,Toyama, Yoshiaki 한림대학교 환경·생명과학연구소 2003 [일송 국제심포지엄] 노화와 만성퇴행성 신경질환 Vol.- No.5
Thanks to advances in the stem cell biology of the central nervous system (CNS), the previously inconceivable regeneration of the damaged CNS is approaching reality. The availability of signals to induce the appropriate differentiation of the transplanted and/or endogenous neural stem cells(NSCs) as well as the timing of the transplantation are important for successful functional recovery of the damaged CNS. Because the immediately post-traumatic microenvironment of the spinal cord is in an acute inflammatory stage, it is not favorable for the survival and differentiation of NSC transplants. On the other hand, in the chronic stage after injury, glial scars form in the injured site that inhibit the regeneration of neuronal axons. Thus, we believe that the optimal timing of transplantation is 1-2 weeks after injury.
Takahiro Kitagawa,Narihito Nagoshi,Hideyuki Okano,Masaya Nakamura 대한척추신경외과학회 2022 Neurospine Vol.19 No.4
A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.
Yohei Bamba,Masahiro Nonaka,Natsu Sasaki,Tomoko Shofuda,Daisuke Kanematsu,Hiroshi Suemizu,Yuichiro Higuchi,Ritsuko K. Pooh,Yonehiro Kanemura,Hideyuki Okano,Mami Yamasaki 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.6
Study Design: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. Purpose: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. Overview of Literature: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. Methods: Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. Results: We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newbornderived iPSCs with a combination of neural induction and neurosphere technology. Conclusions: We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.
Kim, Chongtae,Kim, Wook,Lee, Heejin,Ji, Eunbyul,Choe, Yun-Jeong,Martindale, Jennifer L.,Akamatsu, Wado,Okano, Hideyuki,Kim, Ho-Shik,Nam, Suk Woo,Gorospe, Myriam,Lee, Eun Kyung American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.1
<P>Tight regulation of autophagy is critical for the fate of pancreatic β cells. The autophagy protein ATG5 is essential for the formation of autophagosomes by promoting the lipidation of microtubule-associated protein LC3 (light chain 3). However, little is known about the mechanisms that regulate ATG5 expression levels. In this study, we investigated the regulation of ATG5 expression by HuD. The association of HuD with <I>ATG5</I> mRNA was analyzed by ribonucleoprotein complex immunoprecipitation and biotin pulldown assays. HuD expression levels in pancreatic β cells were knocked down via siRNA, elevated by overexpression of a HuD-expressing plasmid. The expression levels of HuD, ATG5, LC3, and β-actin were determined by Western blot and quantitative RT-PCR analysis. Autophagosome formation was assessed by fluorescence microscopy in GFP-LC3-expressing cells and in pancreatic tissues from WT and HuD-null mice. We identified <I>ATG5</I> mRNA as a post-transcriptional target of the mammalian RNA-binding protein HuD in pancreatic β cells. HuD associated with the 3′-UTR of the <I>ATG5</I> mRNA. Modulating HuD abundance did not alter <I>ATG5</I> mRNA levels, but HuD silencing decreased <I>ATG5</I> mRNA translation, and, conversely, HuD overexpression enhanced <I>ATG5</I> mRNA translation. Through its effect on ATG5, HuD contributed to the lipidation of LC3 and the formation of LC3-positive autophagosomes. In keeping with this regulatory paradigm, HuD-null mice displayed lower ATG5 and LC3 levels in pancreatic β cells. Our results reveal HuD to be an inducer of ATG5 expression and hence a critical regulator of autophagosome formation in pancreatic β cells.</P>
Keisuke Yonamine,Shinsuke Koshita,Yoshihide Kanno,Takahisa Ogawa,Hiroaki Kusunose,Toshitaka Sakai,Kazuaki Miyamoto,Fumisato Kozakai,Hideyuki Anan,Haruka Okano,Masaya Oikawa,Takashi Tsuchiya,Takashi Sa 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.4
Background/Aims: We aimed to investigate (1) promising clinical findings for the recognition of focal type autoimmune pancreatitis (FAIP) and (2) the impact of endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) on the diagnosis of FAIP. Methods: Twenty-three patients with FAIP were involved in this study, and 44 patients with resected pancreatic ductal adenocarcinoma (PDAC) were included in the control group. Results: (1) Multivariate analysis revealed that homogeneous delayed enhancement on contrast-enhanced computed tomography was a significant factor indicative of FAIP compared to PDAC (90% vs. 7%, p=0.015). (2) For 13 of 17 FAIP patients (76.5%) who underwent EUS-TA, EUS-TA aided the diagnostic confirmation of AIPs, and only one patient (5.9%) was found to have AIP after surgery. On the other hand, of the six patients who did not undergo EUS-TA, three (50.0%) underwent surgery for pancreatic lesions. Conclusions: Homogeneous delayed enhancement on contrast-enhanced computed tomography was the most useful clinical factor for discriminating FAIPs from PDACs. EUS-TA is mandatory for diagnostic confirmation of FAIP lesions and can contribute to a reduction in the rate of unnecessary surgery for patients with FAIP.
Hiroaki Kusunose,Shinsuke Koshita,Yoshihide Kanno,Takahisa Ogawa,Toshitaka Sakai,Keisuke Yonamine,Kazuaki Miyamoto,Fumisato Kozakai,Hideyuki Anan,Kazuki Endo,Haruka Okano,Masaya Oikawa,Takashi Tsuchiy 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.3
Background/Aims: This study aimed to clarify the efficacy and safety of pancreatic duct lavage cytology combined with a cell-block method (PLC-CB) for possible pancreatic ductal adenocarcinomas (PDACs). Methods: This study included 41 patients with suspected PDACs who underwent PLC-CB mainly because they were unfit for undergoing endoscopic ultrasonography-guided fine needle aspiration. A 6-Fr double lumen catheter was mainly used to perform PLC-CB. Final diagnoses were obtained from the findings of resected specimens or clinical outcomes during surveillance after PLC-CB. Results: Histocytological evaluations using PLC-CB were performed in 87.8% (36/41) of the patients. For 31 of the 36 patients, final diagnoses (invasive PDAC, 12; pancreatic carcinoma in situ, 5; benignancy, 14) were made, and the remaining five patients were excluded due to lack of surveillance periods after PLC-CB. For 31 patients, the sensitivity, specificity, and accuracy of PLC-CB for detecting malignancy were 94.1%, 100%, and 96.8%, respectively. In addition, they were 87.5%, 100%, and 94.1%, respectively, in 17 patients without pancreatic masses detectable using endoscopic ultrasonography. Four patients developed postprocedural pancreatitis, which improved with conservative therapy. Conclusions: PLC-CB has an excellent ability to detect malignancies in patients with possible PDACs, including pancreatic carcinoma in situ.