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Observation of Positively Charged Magnetic Nanoparticles Inside HepG2 Spheroids Using Electron Microscopy. HepG2球体内带正电磁性纳米颗粒的电镜观察。
Cell medicine Pub Date : 2013-05-14 DOI: 10.3727/215517913X666530
Y. Miyamoto, Yumie Koshidaka, H. Noguchi, Koichi Oishi, Hiroaki Saito, H. Yukawa, N. Kaji, T. Ikeya, Satoshi Suzuki, Hisashi Iwata, Y. Baba, K. Murase, S. Hayashi
{"title":"Observation of Positively Charged Magnetic Nanoparticles Inside HepG2 Spheroids Using Electron Microscopy.","authors":"Y. Miyamoto, Yumie Koshidaka, H. Noguchi, Koichi Oishi, Hiroaki Saito, H. Yukawa, N. Kaji, T. Ikeya, Satoshi Suzuki, Hisashi Iwata, Y. Baba, K. Murase, S. Hayashi","doi":"10.3727/215517913X666530","DOIUrl":"https://doi.org/10.3727/215517913X666530","url":null,"abstract":"Magnetic resonance imaging (MRI) using magnetic nanoparticles has been used to diagnose vascular diseases as well as to monitor transplanted cells and tissues. In this study, we synthesized magnetic iron oxide nanoparticles (TMADM-03), electrically charged by the presence of a cationic end-group substitution of dextran, and observed these nanoparticles inside three-dimensional models of HepG2 spheroids, which mimic tissues. Patterned cell array glass disks were prepared to visualize the presence of TMADM-03 uptaken by HepG2 spheroids using transmission electron microscopy (TEM). The HepG2 cells (2 × 10(5) cells) were inoculated onto Cell-able™ 12-well plates. After 48 h of culture, the cells were incubated with 75 µg Fe/ml TMADM-03 in culture medium for 24 h. To investigate the cellular function of the HepG2 spheroids, the albumin secretion was evaluated by an ELISA. The albumin secretion after incubation for 24 h was reduced compared with the secretion prior to the addition of TMADM-03. TEM image samples were prepared in a planar direction or a vertical direction to the HepG2 spheroids on patterned cell array glass disks. The incorporation of TMADM-03 inside the HepG2 spheroids was confirmed. In addition, TMADM-03 could be observed in the deeper layers of the spheroids, and this was localized in the lysosomes. These data suggest that the novel magnetic iron oxide nanoparticles invade three-dimensional HepG2 spheroids.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X666530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Long-Expected New Start. 期待已久的新开始。
Cell medicine Pub Date : 2013-05-14 DOI: 10.3727/215517913X672245
H. Noguchi
{"title":"Long-Expected New Start.","authors":"H. Noguchi","doi":"10.3727/215517913X672245","DOIUrl":"https://doi.org/10.3727/215517913X672245","url":null,"abstract":"On behalf of the Japan Society for Organ Preservation and Medical Biology (JSOPMB), I express my sincere appreciation to Professor Paul R. Sanberg (Department of Neurosurgery, College of Medicine, University of South Florida, FL, USA), Executive Editor of Cell Medicine, for providing us such an excellent opportunity to publish the data that were presented at the annual meeting of JSOPMB. I also thank Dr. David Eve, Associate Editor of Cell Medicine, for editing our papers in detail. I am very sure that the relationship between Cell Medicine and JSOPMB has enhanced the motivation of JSOPMB members as well as board members and will continue to do so in the future, while also encouraging young Japanese researchers to newly join this organization. \u0000 \u0000Cell-based therapy is one of the most important medical fields in JSOPMB because this form of therapy can be useful for a wide range of diseases. Addressing the current problem of severe human donor organ shortage for cell therapies is a big challenge. Research on adult and embryonic stem cells and artificial cell development, in addition to the recent and rapidly evolving invention of induced pluripotent stem (iPS) cells, encourages us to address the problems confronting cell transplantation. Therefore, JSOPMB has now importantly focused on regenerative medicine in collaboration with cell biologists. \u0000 \u0000One of the extremely important missions of the annual meeting of JSOPMB is to exchange new research outcomes and create new therapeutic concepts. JSOPMB always encourages and motivates young investigators. JSOPMB was started in 1974 for the study of organ preservation and developed widely in the 1990s with the participation of researchers in various fields of medicine, pharmacology, engineering, veterinary medicine, and basic science. Currently, JSOPMB has more than 400 members and is run under the direction of Dr. Takehide Asano, the current President of JSOPMB. \u0000 \u0000Excellent presentations conducted at the 38th annual meeting of JSOPMB held on November 25–26, 2011, in Miyagi, Japan, under the supervision of Dr. Takashi Kondo (Professor, Department of Thoracic Surgery, Tohoku University, Miyagi, Japan) were selected and given an opportunity to be published in this special issue of Cell Medicine. Nine of these presentations are herein published in this special JSOPMB issue. \u0000 \u0000Teratani and Kobayashi reviewed results from various groups using their transgenic rats for direct visualization of their tissues at the bench level and in cell transplantation research. This included studies on renal and liver injury, parkinsonian models, and nerve injury and islet isolation. \u0000 \u0000Diabetes continued to be a major focus with two review papers evaluating different aspects of islet transplantation. Kataoka and Noguchi reviewed the relationship between ER stress and the pathogenesis of type 1 and type 2 diabetes and the association between islet transplantation and ER stress. Maruyama et al. reviewed autologous islet tran","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X672245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human Liver Progenitor Cells for Liver Repair. 用于肝脏修复的人肝祖细胞。
Cell medicine Pub Date : 2013-04-29 eCollection Date: 2013-08-10 DOI: 10.3727/215517913X666459
Catherine A Lombard, Julie Prigent, Etienne M Sokal
{"title":"Human Liver Progenitor Cells for Liver Repair.","authors":"Catherine A Lombard, Julie Prigent, Etienne M Sokal","doi":"10.3727/215517913X666459","DOIUrl":"10.3727/215517913X666459","url":null,"abstract":"<p><p>Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end-stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome. </p>","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X666459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats With Neonatal Hypoxic-Ischemic Encephalopathy. 人脂肪组织源性间充质干细胞移植修复新生儿缺氧缺血性脑病大鼠神经行为障碍。
Cell medicine Pub Date : 2013-02-07 DOI: 10.3727/215517913X658936
Dongsun Park, S. H. Lee, Dae-Kwon Bae, Yun-Hui Yang, Goeun Yang, Jangbeen Kyung, Dajeong Kim, E. Choi, J. Hong, I. Shin, S. Kang, J. Ra, Yun-Bae Kim
{"title":"Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats With Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Dongsun Park, S. H. Lee, Dae-Kwon Bae, Yun-Hui Yang, Goeun Yang, Jangbeen Kyung, Dajeong Kim, E. Choi, J. Hong, I. Shin, S. Kang, J. Ra, Yun-Bae Kim","doi":"10.3727/215517913X658936","DOIUrl":"https://doi.org/10.3727/215517913X658936","url":null,"abstract":"Improving the effects of human adipose tissue-derived mesenchymal stem cells (ASCs) on the demyelination and neurobehavioral function was investigated in an experimental model of neonatal hypoxic-ischemic encephalopathy (HIE). Seven-day-old male rats were subjected to hypoxia-ischemia-lipopolysaccharide and intracerebroventricularly transplanted with human ASCs (4 × 10(5) cells/rat) once at postnatal day 10 (PND10) or repeatedly at PND10, 17, 27, and 37. Neurobehavioral abnormalities (at PND20, 30, and 40) and cognitive functions (at PND41-44) were evaluated using multiple test systems. Human ASCs recovered the using ratio of forelimb contralateral to the injured brain, improved locomotor activity, and restored rota-rod performance of HIE animals, in addition to showing a marked improvement of cognitive functions. It was confirmed that transplanted human ASCs migrated to injured areas and differentiated into oligodendrocytes expressing myelin basic protein (MBP). Moreover, transplanted ASCs restored production of growth and neurotrophic factors and expression of decreased inflammatory cytokines, leading to attenuation of host MBP loss. The results indicate that transplanted ASCs restored neurobehavioral functions by producing MBP as well as by preserving host myelins, which might be mediated by ASCs' anti-inflammatory activity and release of growth and neurotrophic factors.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X658936","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS. 简单机械灌注可显著提高缺血和新鲜大鼠肝脏的肝细胞产量。
Cell medicine Pub Date : 2013-01-01 DOI: 10.3727/215517912X658927
Maria-Louisa Izamis, Candice Calhoun, Basak E Uygun, Maria Angela Guzzardi, Gavrielle Price, Martha Luitje, Nima Saeidi, Martin L Yarmush, Korkut Uygun
{"title":"SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS.","authors":"Maria-Louisa Izamis, Candice Calhoun, Basak E Uygun, Maria Angela Guzzardi, Gavrielle Price, Martha Luitje, Nima Saeidi, Martin L Yarmush, Korkut Uygun","doi":"10.3727/215517912X658927","DOIUrl":"10.3727/215517912X658927","url":null,"abstract":"<p><p>The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3 hour room temperature (20±2°C) machine perfusion protocol to treat non-premedicated livers exposed to 1 hour of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated and untreated ischemic livers using viable hepatocyte yields and <i>in vitro</i> performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers, and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Further, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized.</p>","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X658927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32843227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Cell Persistence of Allogeneic Keratinocytes and Fibroblasts Applied in a Fibrin Matrix to Acute, Full Thickness Wounds. 同种异体角化细胞和成纤维细胞在纤维蛋白基质中应用于急性全层伤口的细胞持久性。
Cell medicine Pub Date : 2013-01-01 DOI: 10.3727/215517912X653346
J. Dickerson, J. Planz, B. Reece, Kathy A Weedon, Sandy D Kirkpatrick, H. Slade
{"title":"Cell Persistence of Allogeneic Keratinocytes and Fibroblasts Applied in a Fibrin Matrix to Acute, Full Thickness Wounds.","authors":"J. Dickerson, J. Planz, B. Reece, Kathy A Weedon, Sandy D Kirkpatrick, H. Slade","doi":"10.3727/215517912X653346","DOIUrl":"https://doi.org/10.3727/215517912X653346","url":null,"abstract":"HP802-247 is a living cell suspension of cultured allogeneic growth-arrested human male keratinocytes and fibroblasts (1:9 ratio), intended for spray application to chronic wounds. In this study, a small wound was created on the arms of 28 healthy female volunteers (3-mm punch), followed by a single application of HP802-247. At each subsequent week for 8 weeks, a punch excision of the wounds was performed on a cohort of three subjects. Excised specimens were analyzed for allogeneic fibroblast and keratinocyte DNA determined by Y-chromosome short-tandem repeats using PCR amplification followed by capillary electrophoresis, a method with estimated sensitivity of 1 male cell in a background of 8,000 female cells. A complete haplotype attributable to HP802-247 fibroblasts was detected in three of three samples at 1 week, with one partial and one complete fibroblast haplotype detected at 2 weeks, and one partial keratinocyte haplotype detected at 3 weeks postapplication. The findings indicate that HP802-247 can be expected to persist in an acute wound bed for up to 2 weeks postapplication.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X653346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells. 人蜕膜间充质细胞是人类诱导多能干细胞的重要来源。
Cell medicine Pub Date : 2012-11-01 DOI: 10.3727/215517912X658918
T. Shofuda, D. Kanematsu, H. Fukusumi, A. Yamamoto, Yohei Bamba, S. Yoshitatsu, H. Suemizu, Masato Nakamura, Y. Sugimoto, M. Furue, A. Kohara, W. Akamatsu, Y. Okada, H. Okano, M. Yamasaki, Y. Kanemura
{"title":"Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells.","authors":"T. Shofuda, D. Kanematsu, H. Fukusumi, A. Yamamoto, Yohei Bamba, S. Yoshitatsu, H. Suemizu, Masato Nakamura, Y. Sugimoto, M. Furue, A. Kohara, W. Akamatsu, Y. Okada, H. Okano, M. Yamasaki, Y. Kanemura","doi":"10.3727/215517912X658918","DOIUrl":"https://doi.org/10.3727/215517912X658918","url":null,"abstract":"Placental tissue is a biomaterial with remarkable potential for use in regenerative medicine. It has a three-layer structure derived from the fetus (amnion and chorion) and the mother (decidua), and it contains huge numbers of cells. Moreover, placental tissue can be collected without any physical danger to the donor and can be matched with a variety of HLA types. The decidua-derived mesenchymal cells (DMCs) are highly proliferative fibroblast-like cells that express a similar pattern of CD antigens as bone marrow-derived mesenchymal cells (BM-MSCs). Here we demonstrated that induced pluripotent stem (iPS) cells could be efficiently generated from DMCs by retroviral transfer of reprogramming factor genes. DMC-hiPS cells showed equivalent characteristics to human embryonic stem cells (hESCs) in colony morphology, global gene expression profile (including human pluripotent stem cell markers), DNA methylation status of the OCT3/4 and NANOG promoters, and ability to differentiate into components of the three germ layers in vitro and in vivo. The RNA expression of XIST and the methylation status of its promoter region suggested that DMC-iPSCs, when maintained undifferentiated and pluripotent, had three distinct states: (1) complete X-chromosome reactivation, (2) one inactive X-chromosome, or (3) an epigenetic aberration. Because DMCs are derived from the maternal portion of the placenta, they can be collected with the full consent of the adult donor and have considerable ethical advantages for cell banking and the subsequent generation of human iPS cells for regenerative applications.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X658918","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Higher Sensitivity of Peripheral Blood Lymphocytes to Endogenous Glucocorticoid in Renal Transplant Recipients Treated With Tacrolimus, as Compared to Those Treated With Cyclosporine. 与环孢素相比,他克莫司治疗的肾移植受者外周血淋巴细胞对内源性糖皮质激素的敏感性更高。
Cell medicine Pub Date : 2012-11-01 DOI: 10.3727/215517912X639423
Gulimire Muhetaer, H. Takeuchi, Sogo Akizuki, H. Iwamoto, M. Shimazu, S. Unezaki, T. Hirano
{"title":"Higher Sensitivity of Peripheral Blood Lymphocytes to Endogenous Glucocorticoid in Renal Transplant Recipients Treated With Tacrolimus, as Compared to Those Treated With Cyclosporine.","authors":"Gulimire Muhetaer, H. Takeuchi, Sogo Akizuki, H. Iwamoto, M. Shimazu, S. Unezaki, T. Hirano","doi":"10.3727/215517912X639423","DOIUrl":"https://doi.org/10.3727/215517912X639423","url":null,"abstract":"Lymphocyte sensitivity to endogenous glucocorticoid cortisol could be a biological marker for safe reduction and withdrawal of steroids in renal transplant recipients. We compared peripheral lymphocyte sensitivity with cortisol between transplant recipients treated with tacrolimus (Tac) and those treated with cyclosporine. The suppressive efficacies of cortisol against T-cell mitogen-stimulated proliferation of peripheral lymphocytes were investigated in 44 renal transplant patients, who either had reduced or been withdrawn from steroid treatment. Twenty of the 44 patients were treated with Tac, and the other 24 patients were treated with cyclosporine A (CyA). The lymphocyte sensitivity to cortisol was compared between these two patient groups. The cortisol IC50 values in the Tac and CyA groups were 0.09 ± 0.12 and 14.2 ± 12.7 ng/ml, respectively. Lymphocyte sensitivity to cortisol in the Tac-treated group was significantly higher than that in the CyA-treated group (p = 0.0283). On the other hand, incidences of steroid withdrawal syndrome and increases in serum creatinine concentration were not significantly different between the Tac and CyA groups. Lymphocyte sensitivity to cortisol was higher in the Tac-treated patients than that in the CyA-treated ones. Since the cortisol sensitivity of peripheral lymphocytes is suggested to be a predictive marker for safe steroid withdrawal, Tac administration shows promise in aiding successful withdrawal of steroid treatment in long-term renal transplant recipients.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X639423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The Effect of CXCR4 Overexpression on Mesenchymal Stem Cell Transplantation in Ischemic Stroke. CXCR4过表达对缺血性脑卒中间充质干细胞移植的影响。
Cell medicine Pub Date : 2012-07-01 DOI: 10.3727/215517912X647172
O. Bang, K. S. Jin, Mi Na Hwang, H. Kang, B. Kim, Sang Jin Lee, S. Kang, Y. Hwang, J. Ahn, K. Sung
{"title":"The Effect of CXCR4 Overexpression on Mesenchymal Stem Cell Transplantation in Ischemic Stroke.","authors":"O. Bang, K. S. Jin, Mi Na Hwang, H. Kang, B. Kim, Sang Jin Lee, S. Kang, Y. Hwang, J. Ahn, K. Sung","doi":"10.3727/215517912X647172","DOIUrl":"https://doi.org/10.3727/215517912X647172","url":null,"abstract":"There is no doubt that the therapeutic efficacy of mesenchymal stem cells (MSCs) needs improvement. SDF-1 (chemokine for MSC homing) and its receptor CXCR4 play a critical role in the migration of MSCs in ischemia. We investigated the effects of the therapeutic application of MSCs transfected to overexpress CXCR4 using an adenoviral construct in the rat stroke model. Both flow cytometry and Western blot analysis indicated that the level of CXCR4 expression was low in naive hMSCs but was consistently high in CXCR4-hMSCs. In vivo migration test using the transwell system showed that the degree of migration was increased in CXCR4-hMSCs compared with the naive hMSCs and was completely blocked by treatment with AMD3100, an antagonist of the CXCR4 receptor. Compared with rats that received naive MSCs, behavioral recovery was more pronounced in rats that received CXCR4-hMSCs (p = 0.023). An immunohistochemistry study using human nuclear antibody (NuMA) showed that the migration of hMSCs in the ischemic boundary zone was increased after 3 days of injection of CXCR4-hMSCs compared with after injection of naive hMSCs. In addition, polymerase chain reaction was performed to assess the biodistribution of human-specific DNA outside the brain after intravenous injection of hMSCs. The expression of human-specific DNA was increased in the lungs of rats receiving naive MSCs, whereas the human-specific DNA expression was increased in the brain of rats receiving CXCR4-hMSCs. Our results indicate that MSCs transfected with the CXCR4 gene expression cassette may be useful in the treatment of cerebral infarction and may represent a new strategy to enhance the efficacy of MSC therapy.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X647172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 24
Behavior of Human Articular Chondrocytes During In Vivo Culture in Closed, Permeable Chambers. 人关节软骨细胞在封闭、可渗透腔体内培养过程中的行为。
Cell medicine Pub Date : 2012-07-01 DOI: 10.3727/215517912X647226
I. Martinez-Zubiaurre, Tuija Annala, M. Polacek
{"title":"Behavior of Human Articular Chondrocytes During In Vivo Culture in Closed, Permeable Chambers.","authors":"I. Martinez-Zubiaurre, Tuija Annala, M. Polacek","doi":"10.3727/215517912X647226","DOIUrl":"https://doi.org/10.3727/215517912X647226","url":null,"abstract":"The exact contribution of transplanted chondrocytes for cartilage tissue repair prior expansion in monolayer culures remains undetermined. At our laboratory, we have created a new permeable chamber to study the chondrogenesis of dedifferentiated cells implanted ectopically in a closed and controlled environment. The behavior of chondrocytes has been studied in settings frequently used in clinical approaches during transplantation, namely injection of autologous chondrocyte cells in suspension (ACI), cells soaked in collagen membranes (MACI), and cells applied in a polymer gel (fibrin). As controls, we have tested the redifferentiation of chondrocytes in cell aggregates, and we have checked the proper functionality of chambers both in vitro and in vivo. After retrieval, firmed tissue-like shapes were recovered only from chambers containing cells seeded in membranes. Histomorphological, immunohistochemical, and ultrastructural analyses revealed synthesis of fibrous-like tissue, characterized by low-density collagen fibers, low collagen type II, abundant collagen type I, and low amounts of proteoglycans. Additionally, neither the collagen membranes nor the fibrin gel was reabsorbed by cells. In summary, our results show that the newly developed permeable chambers function correctly, allowing proper cell feeding and preventing cell leakage or host cell invasion. Additionally, our results suggest that, under these circumstances, chondrocytes are not able to orchestrate formation of hyaline cartilage and have little capacity to degrade artificial membranes or carrier gels such as fibrin. These are interesting observations that should be considered for understanding what role the transplanted chondrocytes play during restoration of articular cartilage after implantation.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517912X647226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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