• Title/Summary/Keyword: differentiation therapy

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In Vitro Differentiation-induced hES Cells Relieve Symptomatic Motor Behavior of PD Animal Model

  • 이창현;김은경;이영재;주완석;조현정;길광수;이금실;신현아;안소연
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.95-95
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    • 2002
  • Human embryonic stem (hES) cells can be induced to differentiate into tyrosine hydroxylase expressing (TH+) cells that may serve as an alternative for cell replacement therapy for Parkinson's disease (PD). To examine in vitro differentiation of hES (MB03, registered in NIH) cells into TH+ cells, hES cells were induced to differentiate according to the 4-/4+ protocol using retinoic acid (RA), ascorbic acid (AA), and/or lithium chloride (LiCl) followed by culture in N2 medium for 14 days, during which time the differentiation occurs. Immunocytochemical stainings of the cells revealed that approximately 21.1% of cells treated with RA plus AA expressed TH protein that is higher than the ratio of TH+ cells seen in any other treatment groups (RA, RA+LiCl or RA+AA+LiCl). In order to see the differentiation pattern in vivo and the ability of in vitro differentiation-induced cells in easing symptomatic motor function of PD animal model, cells (2 $\times$ 10$^{5}$ cells/2${mu}ell$) undergone 4-/4+ protocol using RA plus AA without any further treatment were transplanted into unilateral striatum of MPTP-lesioned PD animal model (C57BL/6). Following the surgery, motor behavior of the animals was examined by measuring the retention time on an accelerating rotar-rod far next 10 weeks. No significant differences in retention time of the animals were noticed until 2 weeks post-graft; however, it increased markedly at 6 weeks and 10 weeks time point after the surgery. Immunohistochemical studies confirmed that a reasonable number of TH+ cells were found at the graft site as well as other remote sites, showing the migrating nature of embryonic stem cells. These results suggest that in viかo differentiated hES cells relieve symptomatic motor behavior of PD animal model and should be considered as a promising alternative for the treatment of PD.

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Inhibitory Effect on RANKL-Induced Osteoclast Differentiation by Water Extract of Zizyphus Jujuba Mill (대추 물 추출물이 RANKL에 의해 유도되는 파골세포 분화에 미치는 영향)

  • Yoon, Kang Hugh;Baek, Jong Min;Kim, Ju Young;Kwak, Seong Cheoul;Cheon, Yoon Hee;Jeon, Byung Hoon;Lee, Chang Hoon;Choi, Min Kyu;Oh, Jaemin;Lee, Myeung Su;Kim, Jeong Joong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.1
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    • pp.29-34
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    • 2014
  • Bone homeostasis is maintained by balance between bone resorbing-osteoclasts and bone forming-osteoblasts. Excessive osteoclastic bone resorption plays a critical role in bone destruction in pathological bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. Many compounds derived from natural products have pharmacological applications and have therapeutic value for treating or preventing several bone diseases characterized by excessive bone resorption. To discover new compounds that can act as anti-resorptive agents, we screened for natural compounds that regulate osteclast differentiation, and found that water extract of Ziziphus Jujuba Mill (WEZJ) has inhibitory effects on osteoclast differentiation. In this study, WEZJ clearly inhibits the osteoclast differentiation in the presence of receptor activator of nuclear factor kB (RANKL), macrophage colony-stimulating factor (M-CSF) without cytoxicity by blocking activation of nuclear factor of activated T cells (NFAT)c1, and c-Fos. In signaling pathway, the phosphorylation of Akt, p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and the expression of osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphates (TRAP), Integrin av, Integrin b3, Cathepsin K are suppressed, too. These result suggest that WEZJ may have therapeutic value for treating or preventing several bone diseases characterized by excessive bone destruction.

Effects of Electroacupuncture and Electrical Stimulation on VEGF Expression After Muscle Crush Injury in Rats (전침 자극과 전기 자극의 적용이 근육압좌손상이 유발된 흰쥐의 골격근 내 혈관내피성장인자 발현에 미치는 영향)

  • Kim, Min-Hee;Lee, Hyun-Min;Park, Eun-Se;Nam, Ki-Won;Kim, Jin-Sang
    • Physical Therapy Korea
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    • v.13 no.2
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    • pp.9-15
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    • 2006
  • Skeletal muscle injury occurs frequently in sports medicine and is the most general form of injury followed by physical impact. There are growth factors which conduct proliferation, differentiation, and synthesis of myogenic prodromal cells and regulate vascular generation for the continued survival of myocytes. The purpose of the present study was to confirm the effects of electroacupuncture (EA) and electrical stimulation (ES) on muscle recovery processes according to vascular endothelial growth factor (VEGF) expression. Eighteen Sprague-Dawley rats were separated into 2 experimental groups and a controlled group. All animals had suffered from crush damage in the extensor digitorum longus for 30 seconds and were killed 1, 3, and 7 days after injury. 30 Hz and 1 mA impulsion for 15 minutes was applied to the EA experimental groups Zusanli (ST36) and Taichong (LR3) using electroacupuncture and the same stimulation was applied to the ES group using an electrical node. Hematoxyline-Eosin staining and VEGF immunohistochemistry were used to ascertain the resulting muscle recovery. There were few morphological differences between the EA and ES groups, and both groups were observed to have tendencies to decrease atrophy as time passed. In the controlled group, gradually diminishing atrophy could be observed, but their forms were mostly disheveled. There were few differences in VEGF expression between the EA and ES groups, and tendencies to have an increased quantity of VEGF with the lapse of time were observed in both groups. In the controlled group, a little VEGF expression could be observed merely 7 days after injury. In conclusion, EA and ES contributed to muscle recovery processes and could be used for the treatment of muscle injury.

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From Bench to Market: Preparing Human Pluripotent Stem Cells Derived Cardiomyocytes for Various Applications

  • Moon, Sung-Hwan;Bae, Daekyeong;Jung, Taek-Hee;Chung, Eun-Bin;Jeong, Young-Hoon;Park, Soon-Jung;Chung, Hyung-Min
    • International Journal of Stem Cells
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    • v.10 no.1
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    • pp.1-11
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    • 2017
  • Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.

The maintenance mechanism of hematopoietic stem cell dormancy: role for a subset of macrophages

  • Cheong-Whan Chae;Gun Choi;You Ji Kim;Mingug Cho;Yoo-Wook Kwon;Hyo-Soo Kim
    • BMB Reports
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    • v.56 no.9
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    • pp.482-487
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    • 2023
  • Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

Optimization of Image Tracking Algorithm Used in 4D Radiation Therapy (4차원 방사선 치료시 영상 추적기술의 최적화)

  • Park, Jong-In;Shin, Eun-Hyuk;Han, Young-Yih;Park, Hee-Chul;Lee, Jai-Ki;Choi, Doo-Ho
    • Progress in Medical Physics
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    • v.23 no.1
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    • pp.8-14
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    • 2012
  • In order to develop a Patient respiratory management system includinga biofeedback function for4-dimentional radiation therapy, this study investigated anoptimal tracking algorithmfor moving target using IR (Infra-red) camera as well as commercial camera. A tracking system was developed by LabVIEW 2010. Motion phantom images were acquired using a camera (IR or commercial). After image process were conducted to convert acquired image to binary image by applying a threshold values, several edge enhance methods such as Sobel, Prewitt, Differentiation, Sigma, Gradient, Roberts, were applied. The targetpattern was defined in the images, and acquired image from a moving targetwas tracked by matching pre-defined tracking pattern. During the matching of imagee, thecoordinateof tracking point was recorded. In order to assess the performance of tracking algorithm, the value of score which represents theaccuracy of pattern matching was defined. To compare the algorithm objectively, we repeat experiments 3 times for 5 minuts for each algorithm. Average valueand standard deviations (SD) of score were automatically calculatedsaved as ASCII format. Score of threshold only was 706, and standard deviation was 84. The value of average and SD for other algorithms which combined edge detection method and thresholdwere 794, 64 in Sobel, 770, 101 in Differentiation, 754, 85 in Gradient, 763, 75 in Prewitt, 777, 93 in Roberts, and 822, 62 in Sigma, respectively. According to score analysis, the most efficient tracking algorithm is the Sigma method. Therefore, 4-dimentional radiation threapy is expected tobemore efficient if threshold and Sigma edge detection method are used together in target tracking.

Differentiation of True Recurrence from Delayed Radiation Therapy-related Changes in Primary Brain Tumors Using Diffusion-weighted Imaging, Dynamic Susceptibility Contrast Perfusion Imaging, and Susceptibility-weighted Imaging (확산강조영상, 역동적조영관류영상, 자화율강조영상을 이용한 원발성 뇌종양환자에서의 종양재발과 지연성 방사선치료연관변화의 감별)

  • Kim, Dong Hyeon;Choi, Seung Hong;Ryoo, Inseon;Yoon, Tae Jin;Kim, Tae Min;Lee, Se-Hoon;Park, Chul-Kee;Kim, Ji-Hoon;Sohn, Chul-Ho;Park, Sung-Hye;Kim, Il Han
    • Investigative Magnetic Resonance Imaging
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    • v.18 no.2
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    • pp.120-132
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    • 2014
  • Purpose : To compare dynamic susceptibility contrast imaging, diffusion-weighted imaging, and susceptibility-weighted imaging (SWI) for the differentiation of tumor recurrence and delayed radiation therapy (RT)-related changes in patients treated with RT for primary brain tumors. Materials and Methods: We enrolled 24 patients treated with RT for various primary brain tumors, who showed newly appearing enhancing lesions more than one year after completion of RT on follow-up MRI. The enhancing-lesions were confirmed as recurrences (n=14) or RT-changes (n=10). We calculated the mean values of normalized cerebral blood volume (nCBV), apparent diffusion coefficient (ADC), and proportion of dark signal intensity on SWI (proSWI) for the enhancing-lesions. All the values between the two groups were compared using t-test. A multivariable logistic regression model was used to determine the best predictor of differential diagnosis. The cutoff value of the best predictor obtained from receiver-operating characteristic curve analysis was applied to calculate the sensitivity, specificity, and accuracy for the diagnosis. Results: The mean nCBV value was significantly higher in the recurrence group than in the RT-change group (P=.004), and the mean proSWI was significantly lower in the recurrence group (P<.001). However, no significant difference was observed in the mean ADC values between the two groups. A multivariable logistic regression analysis showed that proSWI was the only independent variable for the differentiation; the sensitivity, specificity, and accuracy were 78.6% (11 of 14), 100% (10 of 10), and 87.5% (21 of 24), respectively. Conclusion: The proSWI was the most promising parameter for the differentiation of newly developed enhancing-lesions more than one year after RT completion in brain tumor patients.

Interaction between IGFBP-5 and TNFR1

  • Kim, Eun-Jung;Jeong, Mi-Suk;Hwang, Jae-Ryoung;Lee, Je-Ho;Jang, Se-Bok
    • Bulletin of the Korean Chemical Society
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    • v.31 no.7
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    • pp.2019-2024
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    • 2010
  • Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent $K_D$ of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.

Cell-type-specific Gene Expression Patterns in Human Carcinoma Cells followed by Irradiation (방사선에 의한 암세포주 특이적 유전자 발현 양상)

  • Park Ji-Yoon;Kim Jin-Kyu;Chai Young Gyu
    • Korean Journal of Environmental Biology
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    • v.23 no.2 s.58
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    • pp.152-156
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    • 2005
  • Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

SQUAMOUS CELL CARCINOMA WITH APLASTIC ANEMIA PATIENT (재생불량성 빈혈 환자의 편평상피세포암)

  • Lee, Kye-Young;Lee, Ju-Hyun;Min, Kyong-In;Kim, Chul-Whan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.1
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    • pp.65-68
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    • 2001
  • The major manifestations of aplastic anemia are characterized by persistent bone marrow aplasia and peripheral pancytopenia due to defective stem cells in which differentiation is not curtailed or preferential elimination of stem cells with self-renewal capacity, which results in serious complications such as bleeding and infection. Recent advances in the therapeutic modalities, such as bone marrow transplantation and immunosuppressive therapy, and in supportive measures as component transfusion and infection control with better quality of antibiotics resulted in an improved survival and subsequently increased possibility of complications which need surgical intervention. Considering the fact that surgery may not only control complications, but offers the opportunity to give effective therapy for aplastic anemia and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed. We report a case of patient with aplastic anemia who had been performed surgical intervention of partial maxillectomy for the squamous cell carcinoma on maxilla without serious complications during perioperative and postoperative period.

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