WorldWideScience

Sample records for cell therapy pieces

  1. Pieces

    DEFF Research Database (Denmark)

    Jensen, Niels Henrik

    1990-01-01

    The report presents results from the SIP project (System Representation in Process Control). PIECES is a graphical, interactive user interface system designed and programmed as a tool for building, manipulating and using a Multilevel Flow Model (MFM - Morten Lind, Tecnical University of Denmark...

  2. Intraoperative Stem Cell Therapy

    OpenAIRE

    Coelho, Mónica Beato; Cabral, Joaquim M. S.; Karp, Jeffrey M.

    2012-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the poten...

  3. Cell therapy of pseudarthrosis

    OpenAIRE

    Bastos Filho, Ricardo; Lermontov, Simone; Borojevic, Radovan; Schott, Paulo Cezar; Gameiro, Vinicius Schott; José Mauro GRANJEIRO

    2012-01-01

    Objective To assess the safety and efficiency of cell therapy for pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear cells purified extemporaneously using the Sepax® equipment. Methods Six patients with nonunion of the tibia or femur were treated. Four received a percutaneous infusion of autologous bone marrow aspirated from the iliac crest, and two received autologous bone marrow mononuclear cells separated from the aspirate with the Sepax®. The primary fixation ...

  4. Regulatory T cells in health and disease : putting the pieces together

    OpenAIRE

    Vercoulen, Y.

    2010-01-01

    CD4+FOXP3+ Regulatory T cells (Treg) are indispensable for immune balance. In patients with autoimmunity, Treg are either present in lower numbers or not functioning properly and, therefore, inflammation is not suppressed. In murine models and in human studies increase of Treg frequency or function suppresses autoimmunity. Therefore, Treg are important candidates for therapeutic intervention in inflammatory diseases. In order to develop a safe therapy utilizing Treg, it is important to know h...

  5. Cell therapy for spinal cord injury informed by electromagnetic waves.

    Science.gov (United States)

    Finnegan, Jack; Ye, Hui

    2016-10-01

    Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

  6. Nature pieces

    OpenAIRE

    N. Armstrong

    2013-01-01

    Nature pieces was commissioned by Plus-Minus Ensemble, and premiered at Kings Place, London. The work stems from a long-held fascination with the ways in which nature is represented and evoked in music. Specifically, the core technical concerns are addressed to idioms and topics which have historically been put to use in musical 'appeals to nature'; i.e., in constructions and evocations of the idyllic, the folkloric, the archaic, and the hieratic. Topics that are directly engaged include: ped...

  7. Cell Therapy for Multiple Sclerosis

    OpenAIRE

    Ben-Hur, Tamir

    2011-01-01

    The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic pl...

  8. Cell Therapies for Liver Diseases

    Science.gov (United States)

    Yu, Yue; Fisher, James E.; Lillegard, Joseph B.; Rodysill, Brian; Amiot, Bruce; Nyberg, Scott L.

    2011-01-01

    Cell therapies, which include bioartificial liver support and hepatocyte transplantation, have emerged as potential treatments for a variety of liver diseases. Acute liver failure (ALF), acute-on-chronic liver failure, and inherited metabolic liver diseases are examples of liver diseases that have been successfully treated with cell therapies at centers around the world. Cell therapies also have the potential for wide application in other liver diseases, including non-inherited liver diseases and liver cancer, and in improving the success of liver transplantation. Here we briefly summarize current concepts of cell therapy for liver diseases. PMID:22140063

  9. Stem cell therapy for diabetes

    OpenAIRE

    Lee, K. O.; Gan, S U; Calne, R Y

    2012-01-01

    Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced plu...

  10. Stem cell therapy for diabetes

    Directory of Open Access Journals (Sweden)

    K O Lee

    2012-01-01

    Full Text Available Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

  11. Cell Therapy for Cardiovascular Regeneration

    OpenAIRE

    Takehara, Naofumi

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should r...

  12. Trypanosoma cruzi extracellular amastigotes and host cell signaling: more pieces to the puzzle

    Directory of Open Access Journals (Sweden)

    Éden Ramalho Ferreira

    2012-11-01

    Full Text Available Among the different infective stages that Trypanosoma cruzi employs to invade cells, extracellular amastigotes have recently gained attention by our group. This is true primarily because these amastigotes are able to infect cultured cells and animals, establishing a sustainable infective cycle. Extracellular amastigotes are thus an excellent means of adaptation and survival for T. cruzi, whose different infective stages each utilize unique mechanisms for attachment and penetration. Here we discuss some features of host cell invasion by extracellular amastigotes and the associated host cell signaling events that occur as part of the process.

  13. nduced pluripotent stem cells and cell therapy

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2013-12-01

    Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

  14. Nanoparticle induced oxidative stress in cancer cells: adding new pieces to an incomplete jigsaw puzzle.

    Science.gov (United States)

    Nogueira, Daniele Rubert; Rolim, Clarice M Bueno; Farooqi, Ammad Ahmad

    2014-01-01

    Nanotechnology is an emerging field with many promising applications in drug delivery systems. Because of outstanding developments in this field, rapidly increasing research is directed to the development of nanocarriers that may enhance the availability of drugs to the target sites. Substantial fraction of information has been added into the existing scientific literature focusing on the fact that nanoparticles usually generate reactive oxygen species to a greater extent than micro-sized particles. It is worth mentioning that oxidative stress regulates an array of cell signaling cascades that resulted in cancer cell damage. Accumulating experimental evidence over the years has shown that wide-ranging biological mechanisms are triggered by these NPs in cultured cells due to the unique properties of engineered nanoparticles. In this review, we have attempted to provide an overview of the signaling cascades that are activated by oxidative stress in cancer cells in response to different kinds of nanomaterials, including quantum dots, metallic and polymeric nanoparticles.

  15. Regulatory T cells in health and disease : putting the pieces together

    NARCIS (Netherlands)

    Vercoulen, Y.

    2010-01-01

    CD4+FOXP3+ Regulatory T cells (Treg) are indispensable for immune balance. In patients with autoimmunity, Treg are either present in lower numbers or not functioning properly and, therefore, inflammation is not suppressed. In murine models and in human studies increase of Treg frequency or function

  16. The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

    Science.gov (United States)

    Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

    2016-08-01

    Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations. PMID:27322694

  17. Limbal Stem Cell Therapy

    OpenAIRE

    Kringlegarden, Hilde Grane

    2013-01-01

    It is widely accepted today that stem cells in the adult corneal epithelium is located to the limbus. No specific marker of limbal epithelial cells (LESCs) has been identified, yet many have been suggested, including ΔNp63α, ABCG2, vimentin and notch 1. Negative markers include amongst others the differentiation markers Ck3 and Ck12. The lack of an identified specific marker elucidates the need for establishment of more exact molecular markers of LESCs. Limbal stem cell deficiency (LSCD) may ...

  18. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Gene Therapy and Cell Therapy in the News Position Statements Scientists & Clinicians Job Bank General Grant Information ASGCT Grants and Awards ASGCT ... Password New Investigator Resource Center Join ... American Society of Gene & Cell Therapy is the primary professional membership organization for gene and cell therapy. The Society's members ...

  19. Advances in corneal cell therapy.

    Science.gov (United States)

    Fuest, Matthias; Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Mehta, Jodhbir S

    2016-09-01

    Corneal integrity is essential for visual function. Transplantation remains the most common treatment option for advanced corneal diseases. A global donor material shortage requires a search for alternative treatments. Different stem cell populations have been induced to express corneal cell characteristics in vitro and in animal models. Yet before their application to humans, scientific and ethical issues need to be solved. The in vitro propagation and implantation of primary corneal cells has been rapidly evolving with clinical practices of limbal epithelium transplantation and a clinical trial for endothelial cells in progress, implying cultivated ocular cells as a promising option for the future. This review reports on the latest developments in primary ocular cell and stem cell research for corneal therapy. PMID:27498943

  20. Towards personalized regenerative cell therapy

    DEFF Research Database (Denmark)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells...... and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation...... of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing...

  1. Adult Stem Cells and Diabetes Therapy

    OpenAIRE

    Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang

    2015-01-01

    The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cell...

  2. Stem cells: sources and therapies.

    Science.gov (United States)

    Monti, Manuela; Perotti, Cesare; Del Fante, Claudia; Cervio, Marila; Redi, Carlo Alberto

    2012-01-01

    The historical, lexical and conceptual issues embedded in stem cell biology are reviewed from technical, ethical, philosophical, judicial, clinical, economic and biopolitical perspectives. The mechanisms assigning the simultaneous capacity to self-renew and to differentiate to stem cells (immortal template DNA and asymmetric division) are evaluated in the light of the niche hypothesis for the stemness state. The induction of cell pluripotency and the different stem cells sources are presented (embryonic, adult and cord blood). We highlight the embryonic and adult stem cell properties and possible therapies while we emphasize the particular scientific and social values of cord blood donation to set up cord blood banks. The current scientific and legal frameworks of cord blood banks are reviewed at an international level as well as allogenic, dedicated and autologous donations. The expectations and the challenges in relation to present-day targeted diseases like diabetes mellitus type I, Parkinson's disease and myocardial infarction are evaluated in the light of the cellular therapies for regenerative medicine. PMID:23283430

  3. Cell therapy of primary myopathies.

    Science.gov (United States)

    Sampaolesi, M; Biressi, S; Tonlorenzi, R; Innocenzi, A; Draghici, E; Cusella de Angelis, M G; Cossu, G

    2005-09-01

    Mesoangioblasts are multipotent progenitors of mesodermal tissues. In vitro mesoangioblasts differentiate into many mesoderm cell types, such as smooth, cardiac and striated muscle, bone and endothelium. After transplantation mesoangioblasts colonize mostly mesoderm tissues and differentiate into many cell types of the mesoderm. When delivered through the arterial circulation, mesoangioblasts significantly restore skeletal muscle structure and function in a mouse model of muscular dystrophy. Their ability to extensively self-renew in vitro, while retaining multipotency, qualifies mesoangioblasts as a novel class of stem cells. Phenotype, properties and possible origin of mesoangioblasts are addressed in the first part of this paper. In the second part we will focus on the cell therapy approach for the treatment of Muscular Dystrophy and we will describe why mesangioblasts appear to be promising candidates for this strategy.

  4. Stem-cell therapy for neurologic diseases

    Directory of Open Access Journals (Sweden)

    Shilpa Sharma

    2015-01-01

    Full Text Available With the advent of research on stem cell therapy for various diseases, an important need was felt in the field of neurological diseases. While congenital lesion may not be amenable to stem cell therapy completely, there is a scope of partial improvement in the lesions and halt in further progression. Neuro degenerative lesions like Parkinson′s disease, multiple sclerosis and amyotrophic lateral sclerosis have shown improvement with stem cell therapy. This article reviews the available literature and summarizes the current evidence in the various neurologic diseases amenable to stem cell therapy, the plausible mechanism of action, ethical concerns with insights into the future of stem cell therapy.

  5. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    Science.gov (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  6. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma

    OpenAIRE

    Torres, T.; I. Fernandes; Costa, V.; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  7. Stem cell therapy vs. ethics and religion

    OpenAIRE

    Hansen, Paula Melo Paulon; Sloth, Stine Hesselholt

    2009-01-01

    Stem cells are somatic cells that can go through two different kinds of divisions. Symmetric division allows them to divide into undifferentiated cells, whilst asymmetric division produces one undifferentiated cell and a sister cell that will differentiate later on. Human stem cell therapy (HSCT) is a controversial theme in the religious, political, legal, ethical and scientific worlds. Although it is believed by many scientists that stem cell therapy will be able to cure life-threatening dis...

  8. Cell therapy of refractory Crohn's disease.

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Ruchkina, I N; Konoplyannikov, A G

    2013-11-01

    We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy. PMID:24319711

  9. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal a

  10. 三七破壁饮片指纹图谱研究%Study on HPLC Fingerprint Chromatograms of Cell Wall-Broken Decoction Pieces of Notoginseng

    Institute of Scientific and Technical Information of China (English)

    陈炜璇; 刘敏; 严萍; 詹若挺; 陈蔚文; 成金乐

    2012-01-01

    Objective: To establish the HPLC fingerprint chromatograms of crude Notoginseng, cell wall-broken powder and cell wall-broken decoction pieces of Notoginseng and provide evidence for quality control of cell wall-broken decoction pieces of Notoginseng. Methods:The HPLC procedure was performed on the chromatographic column of Hypersil ODS2 ,and the mobile phase was aceto-nitrile and water in gradient elution with the flow velocity of 1. 0 mL/min. The detection wavelength was 203 nm and the column temperature was 25 ℃. The chromatograms was analyzed with the software of "similarity evaluation system for chromatographic fingerprint of TCM". Results:Eight common peaks were pinpointed from the chromatograms of different batches of crude Notoginseng, cell-broken powder and cell-broken decoction pieces, the similarities of the chromatograms were all larger than 0. 9. Conclusion: The method of the HPLC fingerprint chromatogram is of good precision, reproducibility and stability, which is suitable for quality control of cell wall-broken decoction pieces of Notoginseng.%目的:建立三七药材、破壁粉体和破壁饮片的HPLC指纹图谱,为三七破壁饮片的质量控制提供依据.方法:采用高效液相色谱法,Hypersil ODS2色谱柱,流动相:乙腈-水(梯度洗脱),流速:1.0 mL/min,检测波长:203nm,柱温:25℃.采用“中药色谱指纹图谱相似度评价系统”软件对图谱进行分析处理.结果:三七药材、破壁粉体和破壁饮片皂苷类成分指纹图谱标定8个共有峰,三七药材、破壁粉体和破壁饮片之间相似度均大于0.9.结论:建立的HPLC指纹图谱方法具有良好的精密度、重复性和稳定性,适用于三七破壁饮片的质量控制.

  11. Stem Cell Therapy for Heart Failure

    OpenAIRE

    Michler, Robert E.

    2013-01-01

    The last decade has witnessed the publication of a large number of clinical trials primarily using bone marrow-derived stem cells as the injected cell. These “first-generation” clinical trials have advanced our understanding and shown us that (1) cell therapy is safe, (2) cell therapy has been modestly effective, and (3) in humans, bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels (or at least in sufficient numbers to have any effect).

  12. Cell Therapy for Parkinson’s Disease

    OpenAIRE

    Morizane, Asuka; Takahashi, Jun

    2016-01-01

    In Parkinson’s disease (PD), dopamine neurons in the substantia nigra are degenerated and lost. Cell therapy for PD replaces the lost dopamine neurons by transplanting donor dopamine neural progenitor cells. Cell therapy for PD has been performed in the clinic since the 1980s and uses donor cells from the mesencephalon of aborted embryos. Regenerative medicine for PD using induced pluripotent stem (iPS) cell technology is drawing attention, because it offers a limitless and more advantageous ...

  13. Cell Therapy in Chagas Disease

    Directory of Open Access Journals (Sweden)

    Antonio C. Campos de Carvalho

    2009-01-01

    Full Text Available Chagas disease which is caused by the parasite Trypanosoma cruzi is an important cause of cardiomyopathy in Latin America. In later stages chagasic cardiomyopathy is associated with congestive heart failure which is often refractory to medical therapy. In these individuals heart transplantation has been attempted. However, this procedure is fraught with many problems attributable to the surgery and the postsurgical administration of immunosuppressive drugs. Studies in mice suggest that the transplantation of bone-marrow-derived cells ameliorates the inflammation and fibrosis in the heart associated with this infection. Cardiac magnetic resonance imaging reveals that bone marrow transplantation ameliorates the infection induced right ventricular enlargement. On the basis of these animal studies the safety of autologous bone marrow transplantation has been assessed in patients with chagasic end-stage heart disease. The initial results are encouraging and more studies need to be performed.

  14. Effects of initial pH value of the medium on the alcoholic fermentation performance of Saccharomyces cerevisiae cells immobilized on nipa leaf sheath pieces

    OpenAIRE

    Hoang Duc Toan Le; Van Viet Man Le

    2014-01-01

    Immobilized yeast on nipa leaf sheath pieces was applied to ethanol fermentation using the medium with different initial pH values (5.1, 4.5, 4.0, and 3.5). Control samples with the free yeast were also carried out under the same conditions. Low pH value of 4.0 or 3.5 significantly reduced yeast growth and increased the residual sugar level in the fermentation broths for both the immobilized and free cells. In all cases, the ethanol content produced and ethanol formation rate of the ...

  15. Interspecies nuclear transfer using fibroblasts from leopard, tiger, and lion ear piece collected postmortem as donor cells and rabbit oocytes as recipients.

    Science.gov (United States)

    Yelisetti, Uma Mahesh; Komjeti, Suman; Katari, Venu Charan; Sisinthy, Shivaji; Brahmasani, Sambasiva Rao

    2016-06-01

    Skin fibroblast cells were obtained from a small piece of an ear of leopard, lion, and tiger collected postmortem and attempts were made to synchronize the skin fibroblasts at G0/G1 of cell cycle using three different approaches. Efficiency of the approaches was tested following interspecies nuclear transfer with rabbit oocytes as recipient cytoplasm. Fluorescence-activated cell sorting revealed that the proportion of G0/G1 cells increased significantly (P sodium butyrate (NaBu) treatment when compared with cycling cells. However, 3 mM NaBu treatment caused alterations in cell morphology and increase in dead cells. Thus, interspecies nuclear transfer was carried out using fibroblast cells subjected to contact inhibition for 72 h, serum starvation for 48 h, and cells treated with 1.0 mM NaBu for 48 h. The fusion rates, the proportion of fused couplets that cleaved to two-cell and developed to blastocyst, were highest in all three species when the donor cells were treated with 1.0 mM NaBu for 48 h. But, the blastocyst percentage of interspecies nuclear embryos (5-6%) was significantly lower when compared with rabbit-rabbit nuclear transfer embryos (22.9%). In conclusion, fibroblast cells of leopard, lion, and tiger were successfully synchronized and used for the development of blastocysts using rabbit oocytes as recipient cytoplasm. PMID:27071624

  16. Cell therapy for salivary gland regeneration.

    Science.gov (United States)

    Lin, C-Y; Chang, F-H; Chen, C-Y; Huang, C-Y; Hu, F-C; Huang, W-K; Ju, S-S; Chen, M-H

    2011-03-01

    There are still no effective therapies for hyposalivation caused by irradiation. In our previous study, bone marrow stem cells can be transdifferentiated into acinar-like cells in vitro. Therefore, we hypothesized that transplantation with bone marrow stem cells or acinar-like cells may help functional regeneration of salivary glands. Bone marrow stem cells were labeled with nanoparticles and directly co-cultured with acinar cells to obtain labeled acinar-like cells. In total, 140 severely combined immune-deficiency mice were divided into 4 groups for cell therapy experiments: (1) normal mice, (2) mice receiving irradiation around their head-and-neck areas; (3) mice receiving irradiation and intra-gland transplantation with labeled stem cells; and (4) mice receiving irradiation and intra-gland transplantation with labeled acinar-like cells. Our results showed that salivary glands damaged due to irradiation can be rescued by cell therapy with either bone marrow stem cells or acinar-like cells for recovery of saliva production, body weight, and gland weight. Transdifferentiation of bone marrow stem cells into acinar-like cells in vivo was also noted. This study demonstrated that cell therapy with bone marrow stem cells or acinar-like cells can help functional regeneration of salivary glands, and that acinar-like cells showed better therapeutic potentials than those of bone marrow stem cells.

  17. Nonclinical safety strategies for stem cell therapies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  18. Cell-Based Therapies for Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Stella Bernardi

    2012-01-01

    Full Text Available In recent years, accumulating experimental evidence supports the notion that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells. In particular, mesenchymal stem cells and the circulating pool of endothelial progenitor cells have so far been the most studied populations of cells proposed for the treatment of vascular complications affecting diabetic patients. We review the evidence supporting their use in this setting, the therapeutic benefits that these cells have shown so far as well as the challenges that cell-based therapies in diabetic complications put out.

  19. Pluripotent Stem Cells and Gene Therapy

    OpenAIRE

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical s...

  20. A Piece of Cake.

    Science.gov (United States)

    Aceto, Jeffrey T.

    1995-01-01

    A civil engineer describes his first day as a substitute teacher. Despite detailed lesson plans and good intentions, maintaining an orderly class environment is far from a "piece of cake." Recess duty is an ordeal, and lunch in the shabby teacher's lounge is uninspiring. The biggest benefit is appreciation of what constitutes a full-time teacher's…

  1. Effects of initial pH value of the medium on the alcoholic fermentation performance of Saccharomyces cerevisiae cells immobilized on nipa leaf sheath pieces

    Directory of Open Access Journals (Sweden)

    Hoang Duc Toan Le

    2014-12-01

    Full Text Available Immobilized yeast on nipa leaf sheath pieces was applied to ethanol fermentation using the medium with different initial pH values (5.1, 4.5, 4.0, and 3.5. Control samples with the free yeast were also carried out under the same conditions. Low pH value of 4.0 or 3.5 significantly reduced yeast growth and increased the residual sugar level in the fermentation broths for both the immobilized and free cells. In all cases, the ethanol content produced and ethanol formation rate of the immobilized yeast were 13-33% and 35-69%, respectively, higher than those of the free yeast. In addition, the residual sugar content in the immobilized yeast cultures was 2.1-20.5 times lower than that in the free yeast cultures. The yeast immobilized on nipa leaf stem pieces exhibited higher alcoholic fermentation performance than the free yeast in medium with low pH value. This support was potential for further research for application in ethanol industry.

  2. A Piece of Cake

    Institute of Scientific and Technical Information of China (English)

    汪昱

    2006-01-01

    中文和英文都喜欢用“吃”来打比方。我们汉语中有个成语是用来形容一件事特别容易的,就是“小菜一碟”。英语中也有一个成语是差不多的意思:a piece of cake。看来饮食真的是人类的根本啊!和a piece of cake意思相近的还有aseasy as pie、a piece of pie。这两个也是挺有趣的短语。据考证,19世纪的时候pie这个词就用来指“非常容易的事情”了。但是它们确切的起源还是无人知晓。我们用三个例子来具体说明一下:John is very good at mathematics,so thetest was a piece of cake for him.约翰的数学很好,所以这次考试对他来说真是小菜一碟。—You’ll win this swimming competi-tion.—你会赢得这次游泳比赛的。—Why do you say that?—为什么这么说?—Because you can swim much fasterthan the other contestants.It’ll be a piece ofpie!—因为你比其他对手游得快多了。赢得比赛对你来说就是小菜一...

  3. Quality cell therapy manufacturing by design.

    Science.gov (United States)

    Lipsitz, Yonatan Y; Timmins, Nicholas E; Zandstra, Peter W

    2016-04-01

    Transplantation of live cells as therapeutic agents is poised to offer new treatment options for a wide range of acute and chronic diseases. However, the biological complexity of cells has hampered the translation of laboratory-scale experiments into industrial processes for reliable, cost-effective manufacturing of cell-based therapies. We argue here that a solution to this challenge is to design cell manufacturing processes according to quality-by-design (QbD) principles. QbD integrates scientific knowledge and risk analysis into manufacturing process development and is already being adopted by the biopharmaceutical industry. Many opportunities to incorporate QbD into cell therapy manufacturing exist, although further technology development is required for full implementation. Linking measurable molecular and cellular characteristics of a cell population to final product quality through QbD is a crucial step in realizing the potential for cell therapies to transform healthcare.

  4. Introduction to Stem Cell Therapy

    OpenAIRE

    Biehl, Jesse K.; Russell, Brenda

    2009-01-01

    Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cel...

  5. Low Reactive Level Laser Therapy for Mesenchymal Stromal Cells Therapies

    Directory of Open Access Journals (Sweden)

    Toshihiro Kushibiki

    2015-01-01

    Full Text Available Low reactive level laser therapy (LLLT is mainly focused on the activation of intracellular or extracellular chromophore and the initiation of cellular signaling by using low power lasers. Over the past forty years, it was realized that the laser therapy had the potential to improve wound healing and reduce pain and inflammation. In recent years, the term LLLT has become widely recognized in the field of regenerative medicine. In this review, we will describe the mechanisms of action of LLLT at a cellular level and introduce the application to mesenchymal stem cells and mesenchymal stromal cells (MSCs therapies. Finally, our recent research results that LLLT enhanced the MSCs differentiation to osteoblast will also be described.

  6. Challenges for heart disease stem cell therapy

    Directory of Open Access Journals (Sweden)

    Hoover-Plow J

    2012-02-01

    Full Text Available Jane Hoover-Plow, Yanqing GongDepartments of Cardiovascular Medicine and Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USAAbstract: Cardiovascular diseases (CVDs are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1 improved identification, recruitment, and expansion of autologous stem cells; (2 identification of mobilizing and homing agents that increase recruitment; and (3 development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.Keywords: mobilization, expansion, homing, survival, engraftment

  7. Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Mundra, Vaibhav; Gerling, Ivan C.; Mahato, Ram I.

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent adult stem cells which have self-renewal capacity and differentiation potential into several mesenchymal lineages including bones, cartilages, adipose tissues and tendons. MSCs may repair tissue injuries and prevent immune cell activation and proliferation. Immunomodulation and secretion of growth factors by MSCs have led to realizing the true potential of MSC-based cell therapy. The use of MSCs as immunomdulators has been explored in cell/organ t...

  8. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A;

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  9. 菊花破壁饮片的HPLC指纹图谱研究%Study on HPLC Fingerprint of Cell Wall-Broken Decoction Pieces of Chrysanthemi Flos

    Institute of Scientific and Technical Information of China (English)

    刘星云; 王慧玲; 彭丽华; 成金乐

    2016-01-01

    目的:建立菊花破壁饮片HPLC指纹图谱,并分析破壁饮片成品与其中间品、原料的化学成分相关性,为菊花破壁饮片整体质量评价提供依据.方法:采用高效液相色谱法,十八烷基硅烷键合硅胶为填充剂的色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.5%磷酸溶液为流动相进行梯度洗脱,检测波长:348 nm,柱温:35℃.结果:建立了菊花破壁饮片的HPLC指纹图谱,得到了15个共有特征峰,11批样品的相似度达0.98以上,方法学考察结果符合指纹图谱技术要求.结论:所建立的方法稳定、可靠、重复性好,可用于菊花破壁饮片质量控制和综合评价.%Objective:To establish the HPLC fingerprint of Cell Wall-Broken Decoction Pieces of Chrysanthemi Flos, and analyze the relativity between its decoction pieces,broken powder and broken particle,helping to evaluate its quality comprehensively.Methods:RP-HPLC method was performed on an Agilent C18 (250 mm ×4.6 mm,5 μm)column with a gradient elution composed of acetonitrile-aqueous solution containing 0.5% phosphoric acid.The column temperature was set at 35 ℃,while the detective wavelength was set at 348 nm.Results:The chromatographic fingerprint common pattern was established.Fifteen mutual peaks were obtained from the chromatograms of eleven batches of samples.Conclusion:The method with good reproducibility is reliable and stable,which is feasible for quality control of cell wall-broken decoction pieces of Chrysanthemi Flos.

  10. A piece of cake

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    同学们,你们知道a piece of cake的意思吗?这里,我有一个有趣的故事。一个刚到美国的人,由于不懂英语,便到补习学校学习英文。有一天,他问一个同学他没听懂的问题,

  11. [Outlook: Future therapy of renal cell carcinoma].

    Science.gov (United States)

    Bergmann, Lothar; Miller, Kurt

    2010-01-01

    Targeted therapies have fundamentally altered the therapy of metastatic renal cell carcinoma (mRCC). Sunitinib today is an internationally recommended reference standard in first-line therapy; other drugs such as Temsirolimus, Everolimus, Bevacizumab (in combination with Interferon-alpha) and Sorafenib are part of the therapeutic arsenal. Practitioners thus have now more and better therapeutic options at hand, leading to a significantly improved prognosis for mRCC patients. Numerous ongoing research activities aim at the improvement of the benefits of the new compounds in the metastatic situation or application earlier in the course of the disease. Key aspects of future development in RCC are the optimization of the current therapy options by developing new targeted therapies, the search for the best combinations and sequences including the role of nephrectomy and the assessment in the adjuvant or neo-adjuvant setting. The following contribution provides an overview of ongoing studies, thus giving insight into the future therapy of RCC. PMID:20164673

  12. Translational research of adult stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Gen; Suzuki

    2015-01-01

    Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  13. Translational research of adult stem cell therapy.

    Science.gov (United States)

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  14. Pluripotent Stem Cells and Gene Therapy

    Science.gov (United States)

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical studies have demonstrated correction of disease-causing mutations in a number of hematological, neuronal and muscular disorders. This review aims to summarize these recent advances with a focus on iPSC generation techniques, as well as gene modification methods. We will then further discuss some of the main obstacles remaining to be overcome before successful application of human pluripotent stem cell-based therapy arrives in the clinic and what the future of stem cell research may look like. PMID:23353080

  15. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  16. Piece of the sun

    CERN Document Server

    Wayne, Teddy

    2015-01-01

    Our rapidly industrialising world has an insatiable hunger for energy, and conventional sources are struggling to meet demand. Oil is running out, coal is damaging our climate, many nations are abandoning nuclear, yet solar, wind and water will never be a complete replacement. The solution, says Daniel Clery in this deeply researched and revelatory book, is to be found in the original energy source: the Sun itself. There, at its centre, the fusion of 630 million tonnes of hydrogen every second generates an unfathomable amount of energy. By replicating even a tiny piece of the Sun's power

  17. Stem cells in endodontic therapy

    Directory of Open Access Journals (Sweden)

    Sita Rama Kumar M, Madhu Varma K, Kalyan Satish R, Manikya kumar Nanduri.R, Murali Krishnam Raju S, Mohan rao

    2014-11-01

    Full Text Available Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. However, progress in stem cell biology and tissue engineering may present new options for replacing heavily damaged or lost teeth, or even individual tooth structures. The goal of this review is to discuss the potential impact of dental pulp stem cells on regenerative endodontics.

  18. How we make cell therapy in Italy

    Directory of Open Access Journals (Sweden)

    Montemurro T

    2015-08-01

    Full Text Available Tiziana Montemurro, Mariele Viganò, Silvia Budelli, Elisa Montelatici, Cristiana Lavazza, Luigi Marino, Valentina Parazzi, Lorenza Lazzari, Rosaria GiordanoCell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyAbstract: In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.Keywords: advanced therapy medicinal product, good manufacturing practices, stem cells

  19. Gene and cell therapy for muscle regeneration

    OpenAIRE

    Stilhano, Roberta Sessa; Martins, Leonardo; Ingham, Sheila Jean McNeill; Pesquero, João Bosco; Huard, Johnny

    2015-01-01

    Skeletal muscle injury and healing are multifactorial processes, involving three steps of healing: (1) degeneration and inflammation, (2) regeneration, and (3) fibrosis. Fibrous tissue hinders the muscle’s complete recovery and current therapies fail in achieving total muscle recovery. Gene and cell therapy (or both) are potential future treatments for severe muscular injuries. Stem cells’ properties associated with growth factors or/and cytokines can improve muscle healing and permit long-te...

  20. Stem cell therapy independent of stemness

    OpenAIRE

    Lee, Techung

    2012-01-01

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived h...

  1. Strategies for future histocompatible stem cell therapy

    DEFF Research Database (Denmark)

    Nehlin, Jan; Barington, Torben

    2009-01-01

    Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs...... during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated......, genetically identical to the recipient. Once differentiation protocols and culture conditions can be defined and optimized, patient-histocompatible pluripotent stem cells could be directed towards virtually every cell type in the human body. Harnessing this capability to enrich for given cells within...

  2. Stem cell strategies for Alzheimer's disease therapy.

    Science.gov (United States)

    Sugaya, K; Alvarez, A; Marutle, A; Kwak, Y D; Choumkina, E

    2006-06-01

    We have found much evidence that the brain is capable of regenerating neurons after maturation. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for cell-replacement therapies for neurodegenerative diseases including Alzheimer's disease (AD). However, ethical and practical issues associated with HNSCs compel us to explore alternative strategies. Here, we report novel technologies to differentiate adult human mesenchymal stem cells, a subset of stromal cells in the bone marrow, into neural cells by modifying DNA methylation or over expression of nanog, a homeobox gene expressed in embryonic stem cells. We also report peripheral administrations of a pyrimidine derivative that increases endogenous stem cell proliferation improves cognitive function of the aged animal. Although these results may promise a bright future for clinical applications used towards stem cell strategies in AD therapy, we must acknowledge the complexity of AD. We found that glial differentiation takes place in stem cells transplanted into amyloid-( precursor protein (APP) transgenic mice. We also found that over expression of APP gene or recombinant APP treatment causes glial differentiation of stem cells. Although further detailed mechanistic studies may be required, RNA interference of APP or reduction of APP levels in the brain can significantly reduced glial differentiation of stem cells and may be useful in promoting neurogenesis after stem cell transplantation. PMID:16953146

  3. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  4. Cell Therapy for Wound Healing

    OpenAIRE

    You, Hi-Jin; Han, Seung-Kyu

    2014-01-01

    In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin...

  5. Brain repair: cell therapy in stroke

    Directory of Open Access Journals (Sweden)

    Kalladka D

    2014-02-01

    Full Text Available Dheeraj Kalladka, Keith W Muir Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, United Kingdom Abstract: Stroke affects one in every six people worldwide, and is the leading cause of adult disability. Some spontaneous recovery is usual but of limited extent, and the mechanisms of late recovery are not completely understood. Endogenous neurogenesis in humans is thought to contribute to repair, but its extent is unknown. Exogenous cell therapy is promising as a means of augmenting brain repair, with evidence in animal stroke models of cell migration, survival, and differentiation, enhanced endogenous angiogenesis and neurogenesis, immunomodulation, and the secretion of trophic factors by stem cells from a variety of sources, but the potential mechanisms of action are incompletely understood. In the animal models of stroke, both mesenchymal stem cells (MSCs and neural stem cells (NSCs improve functional recovery, and MSCs reduce the infarct volume when administered acutely, but the heterogeneity in the choice of assessment scales, publication bias, and the possible confounding effects of immunosuppressants make the comparison of effects across cell types difficult. The use of adult-derived cells avoids the ethical issues around embryonic cells but may have more restricted differentiation potential. The use of autologous cells avoids rejection risk, but the sources are restricted, and culture expansion may be necessary, delaying treatment. Allogeneic cells offer controlled cell numbers and immediate availability, which may have advantages for acute treatment. Early clinical trials of both NSCs and MSCs are ongoing, and clinical safety data are emerging from limited numbers of selected patients. Ongoing research to identify prognostic imaging markers may help to improve patient selection, and the novel imaging techniques may identify biomarkers of recovery and the mechanism of action for cell

  6. Cyclosporin in cell therapy for cardiac regeneration.

    Science.gov (United States)

    Jansen Of Lorkeers, S J; Hart, E; Tang, X L; Chamuleau, M E D; Doevendans, P A; Bolli, R; Chamuleau, S A J

    2014-07-01

    Stem cell therapy is a promising strategy in promoting cardiac repair in the setting of ischemic heart disease. Clinical and preclinical studies have shown that cell therapy improves cardiac function. Whether autologous or allogeneic cells should be used, and the need for immunosuppression in non-autologous settings, is a matter of debate. Cyclosporin A (CsA) is frequently used in preclinical trials to reduce cell rejection after non-autologous cell therapy. The direct effect of CsA on the function and survival of stem cells is unclear. Furthermore, the appropriate daily dosage of CsA in animal models has not been established. In this review, we discuss the pros and cons of the use of CsA on an array of stem cells both in vitro and in vivo. Furthermore, we present a small collection of data put forth by our group supporting the efficacy and safety of a specific daily CsA dosage in a pig model. PMID:24831573

  7. Cyclosporin in cell therapy for cardiac regeneration.

    Science.gov (United States)

    Jansen Of Lorkeers, S J; Hart, E; Tang, X L; Chamuleau, M E D; Doevendans, P A; Bolli, R; Chamuleau, S A J

    2014-07-01

    Stem cell therapy is a promising strategy in promoting cardiac repair in the setting of ischemic heart disease. Clinical and preclinical studies have shown that cell therapy improves cardiac function. Whether autologous or allogeneic cells should be used, and the need for immunosuppression in non-autologous settings, is a matter of debate. Cyclosporin A (CsA) is frequently used in preclinical trials to reduce cell rejection after non-autologous cell therapy. The direct effect of CsA on the function and survival of stem cells is unclear. Furthermore, the appropriate daily dosage of CsA in animal models has not been established. In this review, we discuss the pros and cons of the use of CsA on an array of stem cells both in vitro and in vivo. Furthermore, we present a small collection of data put forth by our group supporting the efficacy and safety of a specific daily CsA dosage in a pig model.

  8. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  9. How we make cell therapy in Italy.

    Science.gov (United States)

    Montemurro, Tiziana; Viganò, Mariele; Budelli, Silvia; Montelatici, Elisa; Lavazza, Cristiana; Marino, Luigi; Parazzi, Valentina; Lazzari, Lorenza; Giordano, Rosaria

    2015-01-01

    In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product. PMID:26316716

  10. Cell therapies for tendons: old cell choice for modern innovation.

    Science.gov (United States)

    Petrou, Ilias G; Grognuz, Anthony; Hirt-Burri, Nathalie; Raffoul, Wassim; Applegate, Lee Ann

    2014-01-01

    Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.

  11. Adult Stem Cell Therapy for Periodontal Disease

    OpenAIRE

    Kim, Su-Hwan; Seo, Byoung-Moo; Choung, Pill-Hoon; Lee, Yong-Moo

    2010-01-01

    Periodontal disease is a major cause of tooth loss and characterized by inflammation of tooth-supporting structures. Recently, the association between periodontal disease and other health problems has been reported, the importance of treating periodontal disease for general health is more emphasized. The ultimate goal of periodontal therapy is regeneration of damaged periodontal tissues. The development of adult stem cell research enables to improve the cell-based tissue engineering for perio...

  12. Large animal models for stem cell therapy

    OpenAIRE

    Harding, John; Roberts, R. Michael; Mirochnitchenko, Oleg

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  13. Mesenchymal stem cells: a new trend for cell therapy

    Institute of Scientific and Technical Information of China (English)

    Xin WEI; Xue YANG; Zhi-peng HAN; Fang-fang QU; Li SHAO; Yu-fang SHI

    2013-01-01

    Mesenchymal stem cells (MSCs),the major stem cells for cell therapy,have been used in the clinic for approximately 10 years.From animal models to clinical trials,MSCs have afforded promise in the treatment of numerous diseases,mainly tissue injury and immune disorders.In this review,we summarize the recent opinions on methods,timing and cell sources for MSC administration in clinical applications,and provide an overview of mechanisms that are significant in MSC-mediated therapies.Although MSCs for cell therapy have been shown to be safe and effective,there are still challenges that need to be tackled before their wide application in the clinic.

  14. Stem cell therapy for myocardial infarction

    NARCIS (Netherlands)

    A.D. Moelker (Amber)

    2007-01-01

    textabstractCoronary heart disease and heart failure continue to be significant burdens to healthcare systems in the Western world and are predicted to become so in emerging economies. Despite mixed results in both experimental and clinical studies, stem cell therapy is a promising option for

  15. Stem cells - biological update and cell therapy progress.

    Science.gov (United States)

    Girlovanu, Mihai; Susman, Sergiu; Soritau, Olga; Rus-Ciuca, Dan; Melincovici, Carmen; Constantin, Anne-Marie; Mihu, Carmen Mihaela

    2015-01-01

    In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research. The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases. Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues. This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine.

  16. Progress and prospects in stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Xiu-ling XU; Fei YI; Hui-ze PAN; Shun-lei DUAN; Zhi-chao DING; Guo-hong YUAN; Jing QU

    2013-01-01

    In the past few years,progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways.The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials.Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas,including neurological disorders,hematologic diseases,cardiac diseases,liver diseases and etc.On top of this,latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs.Here in this review,we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies.In addition,we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

  17. Cancer Stem Cells, Cancer Cell Plasticity and Radiation Therapy

    OpenAIRE

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be ...

  18. 28. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Henningson, Carl T; Stanislaus, Marisha A; Gewirtz, Alan M

    2003-02-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to be capable of differentiating into skeletal muscle, brain microglia and astroglia, and hepatocytes. Stem cell lines derived from both embryonic stem and embryonic germ cells (from the embryonic gonadal ridge) are pluripotent and capable of self-renewal for long periods. Therefore embryonic stem and germ cells have been widely investigated for their potential to cure diseases by repairing or replacing damaged cells and tissues. Studies in animal models have shown that transplantation of fetal, embryonic stem, or embryonic germ cells may be able to treat some chronic diseases. In this review, we highlight recent developments in the use of stem cells as therapeutic agents for three such diseases: Diabetes, Parkinson disease, and congestive heart failure. We also discuss the potential use of stem cells as gene therapy delivery cells and the scientific and ethical issues that arise with the use of human stem cells. PMID:12592319

  19. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  20. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  1. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  2. Stem cell therapy for retinal diseases

    Institute of Scientific and Technical Information of China (English)

    Jose Mauricio Garcia,; Luisa Mendon?a; Rodrigo Brant; Murilo Abud; Caio Regatieri; Bruno Diniz

    2015-01-01

    In this review, we discuss about current knowledgeabout stem cell (SC) therapy in the treatment of retinaldegeneration. Both human embryonic stem cell andinduced pluripotent stem cell has been growth inculture for a long time, and started to be explored inthe treatment of blinding conditions. The Food andDrug Administration, recently, has granted clinical trialsusing SC retinal therapy to treat complex disorders, asStargardt's dystrophy, and patients with geographicatrophy, providing good outcomes. This study'sintent is to overview the critical regeneration of thesubretinal anatomy through retinal pigment epitheliumtransplantation, with the goal of reestablish importantpathways from the retina to the occipital cortex of thebrain, as well as the differentiation from pluripotentquiescent SC to adult retina, and its relationshipwith a primary retinal injury, different techniques oftransplantation, management of immune rejection andtumorigenicity, its potential application in improvingpatients' vision, and, finally, approaching future directionsand challenges for the treatment of several conditions.

  3. Radiation therapy for intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Shingo; Hayakawa, Kazushige; Tsuchiya, Miwako; Arai, Masahiko; Kazumoto, Tomoko; Niibe, Hideo; Tamura, Masaru

    1988-04-01

    The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1 % for germinomas and 38.1 % for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis iradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.

  4. Stem cell therapy: From bench to bedside

    International Nuclear Information System (INIS)

    Several countries have increased efforts to develop medical countermeasures to protect against radiation toxicity due to acts of bio-terrorism as well as cancer treatment. Both acute radiation injuries and delayed effects such as cutaneous effects and impaired wound repair depend, to some extent, on angiogenesis deficiency. Vascular damage influences levels of nutrients, oxygen available to skin tissue and epithelial cell viability. Consequently, the evolution of radiation lesions often becomes uncontrolled and surgery is the final option-amputation leading to a disability. Therefore, the development of strategies designed to promote healing of radiation injuries is a major therapeutic challenge. Adult mesenchymal stem cell therapy has been combined with surgery in some cases and not in others and successfully applied in patients with accidental radiation injuries. Although research in the field of radiation skin injury management has made substantial progress in the past 10 y, several strategies are still needed in order to enhance the beneficial effect of stem cell therapy and to counteract the deleterious effect of an irradiated tissue environment. This review summarises the current and evolving advances concerning basic and translational research based on stem cell therapy for the management of radiological burns. (authors)

  5. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  6. Stem Cell Therapy for Degenerative Disc Disease

    Directory of Open Access Journals (Sweden)

    Doniel Drazin

    2012-01-01

    Full Text Available Low back pain is widely recognized as one of the most prevalent pathologies in the developed world. In the United States, low back pain is the most common health problem for adults under the age of 50, resulting in significant societal and personal costs. While the causes of low back pain are myriad, it has been significantly associated with intervertebral disc (IVD degeneration. Current first-line therapies for IVD degeneration such as physical therapy and spinal fusion address symptoms, but do not treat the underlying degeneration. The use of tissue engineering to treat IVD degeneration provides an opportunity to correct the pathological process. Novel techniques are currently being investigated and have shown mixed results. One major avenue of investigation has been stem cell injections. Mesenchymal stem cells (MSCs have shown promise in small animal models, but results in larger vertebrates have been mixed.

  7. Cell therapies for pancreatic beta-cell replenishment.

    Science.gov (United States)

    Okere, Bernard; Lucaccioni, Laura; Dominici, Massimo; Iughetti, Lorenzo

    2016-01-01

    The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection. Replacement of pancreatic beta-cells would represent an ideal treatment that could overcome the above mentioned therapeutic hurdles. In this context, transplantation of islets of Langerhans is considered a less invasive procedure although long-term outcomes showed that only 10 % of the patients remained insulin independent five years after the transplant. Moreover, due to shortage of organs and the inability of islet to be expanded ex vivo, this therapy can be offered to a very limited number of patients. Over the past decade, cellular therapies have emerged as the new frontier of treatment of several diseases. Furthermore the advent of stem cells as renewable source of cell-substitutes to replenish the beta cell population, has blurred the hype on islet transplantation. Breakthrough cellular approaches aim to generate stem-cell-derived insulin producing cells, which could make diabetes cellular therapy available to millions. However, to date, stem cell therapy for diabetes is still in its early experimental stages. This review describes the most reliable sources of stem cells that have been developed to produce insulin and their most relevant experimental applications for the cure of diabetes. PMID:27400873

  8. Renal Preservation Therapy for Renal Cell Carcinoma

    OpenAIRE

    Yichun Chiu; Allen W. Chiu

    2012-01-01

    Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy (PN) is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN). Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic partial nephrectomy...

  9. Targeted therapy for metastatic renal cell carcinoma

    OpenAIRE

    Patel, P H; Chaganti, R.S.K.; Motzer, R J

    2006-01-01

    Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib a...

  10. Stem Cell Therapy for Heart Disease

    OpenAIRE

    Puliafico, Shannon B.; Penn, Marc S.; Silver, Kevin H.

    2013-01-01

    Coronary artery disease is the leading cause of death in Americans. After myocardial infarction, significant ventricular damage persists despite timely reperfusion and pharmacological management. Treatment is limited, as current modalities do not cure this damage. In the past decade, stem cell therapy has emerged as a promising therapeutic solution to restore myocardial function. Clinical trials have demonstrated safety and beneficial effects in patients suffering from acute myocardial infarc...

  11. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  12. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  13. Stem cell therapy independent of stemness.

    Science.gov (United States)

    Lee, Techung

    2012-12-26

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived hepatocyte growth factor (HGF) in two animal models of multiple sclerosis (MS), which is a progressive autoimmune disorder caused by damage to the myelin sheath and loss of oligodendrocytes. Although current MS therapies are directed toward attenuation of the immune response, robust repair of myelin sheath likely requires a regenerative approach focusing on long-term replacement of the lost oligodendrocytes. This approach appears feasible because adult organs contain various populations of multipotent resident stem/progenitor cells that may be activated by MSC trophic factors as demonstrated by Bai et al This commentary highlights and discusses the major findings of their studies, emphasizing the anti-inflammatory function and trophic cross-talk mechanisms mediated by HGF and other MSC-derived trophic factors in sustaining the treatment benefits. Identification of multiple functionally synergistic trophic factors, such as HGF and vascular endothelial growth factor, can eventually lead to the development of efficacious cell-free therapeutic regimens targeting a broad spectrum of degenerative conditions. PMID:23516128

  14. Concise Review: Stem Cell Therapy for Muscular Dystrophies

    OpenAIRE

    Wilschut, Karlijn J.; Ling, Vivian B.; Bernstein, Harold S.

    2012-01-01

    Stem cell therapy holds promise as a treatment for muscular dystrophy by providing cells that can both deliver functional muscle proteins and replenish the stem cell pool. This article reviews the current state of research on myogenic stem cells and identifies the important challenges that must be addressed as stem cell therapy is brought to the clinic.

  15. Cell-based therapy - navigating troubled waters.

    Science.gov (United States)

    Pepper, Michael S

    2010-05-04

    Cells and engineered tissue can be used to treat an increasing number of diseases. This development, together with promising pre-clinical data in regenerative medicine, has raised the expectations of many patients. However, this situation tends to make people vulnerable to the lures of companies that abuse the stem cell promise. The problem is compounded by people's propensity to believe that the healing powers of positive thinking, large sums of money and foreign institutions are greater than those of therapies developed through well-tested, properly constructed, clinical trials.

  16. Muscling up damaged hearts through cell therapy

    Institute of Scientific and Technical Information of China (English)

    Chi Van Dang

    2006-01-01

    @@ Molecular and cellular processes gleaned from the most fundamental of biomedical studies are now harnessed for their potential healing properties. In the US and throughout the world, millions of patients suffer from myocardial infarction and many succumb to the morbidity and mortality of the ensuing cardiac failure, a protracted condition in need of healing. While pharmacological agents have been the mainstay intervention that ameliorates cardiac failure through increased contractility or reduction of cardiac workload, these agents do not inherently heal the wounds inflicted by poor perfusion of the affected cardiac tissue.Cell therapy, however, holds the promise of repleting the damage heart with new contractile cells that can be engineered to secrete concoctions that promote healing by recruiting new blood vessel development or angiogenesis.Such cell therapeutic promise has already been fulfilled for many decades for hematological diseases through transplantation of bone marrow stem cells, which are now more broadly implicated for their healing potential of other tissues.

  17. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    Science.gov (United States)

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

  18. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    Science.gov (United States)

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer. PMID:27136938

  19. Investigation progress of imaging techniques monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

  20. Multiple piece turbine rotor blade

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Russell B; Fedock, John A

    2013-05-21

    A multiple piece turbine rotor blade with a shell having an airfoil shape and secured between a spar and a platform with the spar including a tip end piece. a snap ring fits around the spar and abuts against the spar tip end piece on a top side and abuts against a shell on the bottom side so that the centrifugal loads from the shell is passed through the snap ring and into the spar and not through a tip cap dovetail slot and projection structure.

  1. New Insights into Diabetes Cell Therapy.

    Science.gov (United States)

    Lysy, Philippe A; Corritore, Elisa; Sokal, Etienne M

    2016-05-01

    Since insulin discovery, islet transplantation was the first protocol to show the possibility to cure patients with type 1 diabetes using low-risk procedures. The scarcity of pancreas donors triggered a burst of studies focused on the production of new β cells in vitro. These were rapidly dominated by pluripotent stem cells (PSCs) demonstrating diabetes-reversal potential in diabetic mice. Subsequent enthusiasm fostered a clinical trial with immunoisolated embryonic-derived pancreatic progenitors. Yet safety is the Achilles' heel of PSCs, and a whole branch of β cell engineering medicine focuses on transdifferentiation of adult pancreatic cells. New data showed the possibility to chemically stimulate acinar or α cells to undergo β cell neogenesis and provide opportunities to intervene in situ without the need for a transplant, at least after weighing benefits against systemic adverse effects. The current studies suggested the pancreas as a reservoir of facultative progenitors (e.g., in the duct lining) could be exploited ex vivo for expansion and β cell differentiation in timely fashion and without the hurdles of PSC use. Diabetes cell therapy is thus a growing field not only with great potential but also with many pitfalls to overcome for becoming fully envisioned as a competitor to the current treatment standards.

  2. Stem Cell Therapy for Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Gunduz E

    2011-01-01

    Full Text Available IntroductionHeart failure is a major cardiovascular health problem. Coronary artery disease is the leading cause of congestive heart failure (CHF [1]. Cardiac transplantation remains the most effective long-term treatment option, however is limited primarily by donor availability, rejection and infections. Mechanical circulatory support has its own indications and limitations [2]. Therefore, there is a need to develop more effective therapeutic strategies.Recently, regenerative medicine has received considerable scientific attention in the cardiovascular arena. We report here our experience demonstrating the beneficial effects of cardiac stem cell therapy on left ventricular functions in a patient with Hodgkin’s lymphoma (HL who developed CHF due to ischemic heart disease during the course of lymphoma treatment. Case reportA 58-year-old male with relapsed HL was referred to our bone marrow transplantation unit in October 2009. He was given 8 courses of combination chemotherapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD between June 2008 and February 2009 and achieved complete remission. However, his disease relapsed 3 months after completing the last cycle of ABVD and he was decided to be treated with DHAP (cisplatin, cytarabine, dexamethasone followed autologous stem cell transplantation (SCT. After the completion of first course of DHAP regimen, he developed acute myocardial infarction (AMI and coronary artery bypass grafting (CABG was performed. After his cardiac function stabilized, 3 additional courses of DHAP were given and he was referred to our centre for consideration of autologous SCT. Computed tomography scans obtained after chemotherapy confirmed complete remission. Stem cells were collected from peripheral blood after mobilization with 10 µg/kg/day granulocyte colony-stimulating factor (G-CSF subcutaneously. Collection was started on the fifth day of G-CSF and performed for 3 consecutive days. Flow cytometric

  3. Advances in Stem Cell Therapy for Leukemia.

    Science.gov (United States)

    Tian, Hong; Qu, Qi; Liu, Liming; Wu, Depei

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD). In addition, infusion of HLA-mismatched donor granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells after chemotherapy, the so called "microtransplantation", has been shown to promote the graft-versus-leukemia effect and hasten hematopoietic recovery without amplifying GVHD. Herein, we review recent advances in stem cell therapy for leukemia with a specific focus on dual transplantation and microtransplantation.

  4. Kallikrein-kinin in stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Julie; Chao; Grant; Bledsoe; Lee; Chao

    2014-01-01

    The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells(MSCs), endothelial progenitor cells(EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.

  5. T-cell-directed therapies in systemic lupus erythematosus.

    Science.gov (United States)

    Nandkumar, P; Furie, R

    2016-09-01

    Drug development for the treatment of systemic lupus erythematosus (SLE) has largely focused on B-cell therapies. A greater understanding of the immunopathogenesis of SLE coupled with advanced bioengineering has allowed for clinical trials centered on other targets for SLE therapy. The authors discuss the benefits and shortcomings of focusing on T-cell-directed therapies in SLE and lupus nephritis clinical trials.

  6. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. PMID:27106799

  7. Stem Cell-Based Cell Therapy for Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Meiling Jin

    2014-01-01

    Full Text Available Glomerulonephritis (GN, characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells.

  8. Cell-Based Therapy for Silicosis.

    Science.gov (United States)

    Lopes-Pacheco, Miquéias; Bandeira, Elga; Morales, Marcelo M

    2016-01-01

    Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis. PMID:27066079

  9. Cell-Based Therapy for Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2016-01-01

    Full Text Available Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis.

  10. Present and future cell therapies for pancreatic beta cell replenishment

    Institute of Scientific and Technical Information of China (English)

    Juan Domínguez-Bendala; Camillo Ricordi

    2012-01-01

    If only at a small scale,islet transplantation has successfully addressed what ought to be the primary endpoint of any cell therapy:the functional replenishment of damaged tissue in patients.After years of less-thanoptimal approaches to immunosuppression,recent advances consistently yield long-term graft survival rates comparable to those of whole pancreas transplantation.Limited organ availability is the main hurdle that stands in the way of the widespread clinical utilization of this pioneering intervention.Progress in stem cell research over the past decade,coupled with our decades-long experience with islet transplantation,is shaping the future of cell therapies for the treatment of diabetes.Here we review the most promising avenues of research aimed at generating an inexhaustible supply of insulin-producing cells for islet regeneration,including the differentiation of pluripotent and multipotent stem cells of embryonic and adult origin along the beta cell lineage and the direct reprogramming of non-endocrine tissues into insulin-producing cells.

  11. Oncolytic vaccinia therapy of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2009-07-01

    Full Text Available Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68 as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs were observed in four of the cell lines. At a multiplicity of infection (MOI of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.

  12. Stem cell therapy for severe autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Marmont Alberto M.

    2002-01-01

    Full Text Available Intense immunosuppresion followed by alogenic or autogenic hematopoietic stem cell transplantation is a relatively recent procedure which was used for the first time in severe, refractory cases of systemic lupus erythematosus. Currently three agressive procedures are used in the treatment of autoimmune diseases: high dose chemotherapy without stem cell rescue, intense immunosuppression with subsequent infusion of the alogenic hematopoietic stem cell transplantation combined with or without the selection of CD34+ cells, and the autogenic hematopoietic stem cell transplantation. Proof of the graft-versus-leukemia effect observed define SCT as a form of immunotherapy, with additional evidence of an similar Graft-vs-Autoimmunity effect which is suggestive of a cure for autoimmune diseases in this type of therapy. The use of alogenic SCT improved due to its safety compared to autogenic transplantations. In this report, data of multiply sclerosis and systemic lupus erythematosus are reported, with the conclusion that Immunoablation followed by SCT is clearly indicated in such cases.

  13. Radiation Therapy for Cutaneous T-Cell Lymphomas.

    Science.gov (United States)

    Tandberg, Daniel J; Craciunescu, Oana; Kelsey, Chris R

    2015-10-01

    Radiation therapy is an extraordinarily effective skin-directed therapy for cutaneous T-cell lymphomas. Lymphocytes are extremely sensitive to radiation and a complete response is generally achieved even with low doses. Radiation therapy has several important roles in the management of mycosis fungoides. For the rare patient with unilesional disease, radiation therapy alone is potentially curative. For patients with more advanced cutaneous disease, radiation therapy to local lesions or to the entire skin can effectively palliate symptomatic disease and provide local disease control. Compared with other skin-directed therapies, radiation therapy is particularly advantageous because it can effectively penetrate and treat thicker plaques and tumors. PMID:26433843

  14. The Cell Therapy Catapult: growing a U.K. cell therapy industry generating health and wealth.

    Science.gov (United States)

    Thompson, Keith; Foster, Emma Palmer

    2013-12-01

    In a recent report on the regenerative medicine sector, the U.K. House of Lords made several recommendations to enable the United Kingdom to become a global leader in this important industry. Its recommendations in this regard were many and various, covering the regulatory system, clinical trials, manufacturing, funding, approval, and reimbursement. In its mission to tackle what it sees as three main types of barriers to the development of the cell therapy industry in the United Kingdom, the Cell Therapy Catapult is tackling many of these issues. Established as a center of excellence in the United Kingdom in 2012, the Cell Therapy Catapult is a research organization expected to grow to a team of around 100 experts. Its core financing of £ 70 million over the next 5 years is provided by the Technology Strategy Board, the United Kingdom's innovation agency, and with additional contract research income and access to collaborative funds, the Catapult expects to build up to annual revenues of around £ 30 million. Along with its sister Catapult programs in other areas of the economy, the Cell Therapy Catapult was established after identification of the massive early-stage expertise the country has, as well as an acute market failure-the lack of expertise to translate early-stage cell therapy research into commercial success. In this article, in addition to showing our progress so far, we will discuss the hurdles the industry faces-grouped into business, manufacturing/supply chain issues, and clinical/regulatory issues-and what we are doing to help the United Kingdom leap over them. PMID:24304073

  15. Present and future cell therapies for pancreatic beta cell replenishment

    OpenAIRE

    Domínguez-Bendala, Juan; Ricordi, Camillo

    2012-01-01

    If only at a small scale, islet transplantation has successfully addressed what ought to be the primary endpoint of any cell therapy: the functional replenishment of damaged tissue in patients. After years of less-than-optimal approaches to immunosuppression, recent advances consistently yield long-term graft survival rates comparable to those of whole pancreas transplantation. Limited organ availability is the main hurdle that stands in the way of the widespread clinical utilization of this ...

  16. Stem cell therapy for Alzheimer's disease.

    Science.gov (United States)

    Abdel-Salam, Omar M E

    2011-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (Abeta) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain of mice or rats were mostly followed by their incorporation into the host parenchyma and differentiation into functional neural lineages. In the lesioned brain, stem cells exhibited targeted migration towards the damaged regions of the brain, where they engrafted, proliferated and matured into functional neurones. Neural precursor cells can be intravenously administered and yet migrate into brain damaged areas and induce functional recovery. Observations in animal models of AD have provided evidence that transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory deficits. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines and neuronal apoptotic death. Stem cells could also be genetically modified to express growth factors into the brain. In the last years, evidence indicated that the adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute to the

  17. Managing particulates in cell therapy: Guidance for best practice.

    Science.gov (United States)

    Clarke, Dominic; Stanton, Jean; Powers, Donald; Karnieli, Ohad; Nahum, Sagi; Abraham, Eytan; Parisse, Jean-Sebastien; Oh, Steve

    2016-09-01

    The intent of this article is to provide guidance and recommendations to cell therapy product sponsors (including developers and manufacturers) and their suppliers in the cell therapy industry regarding particulate source, testing, monitoring and methods for control. This information is intended to help all parties characterize the processes that generate particulates, understand product impact and provide recommendations to control particulates generated during manufacturing of cell therapy products. PMID:27426934

  18. [Retinal Cell Therapy Using iPS Cells].

    Science.gov (United States)

    Takahashi, Masayo

    2016-03-01

    Progress in basic research, starting with the work on neural stem cells in the middle 1990's to embryonic stem (ES) cells and induced pluripotent stem (iPS) cells at present, will lead the cell therapy (regenerative medicine) of various organs, including the central nervous system to a big medical field in the future. The author's group transplanted iPS cell-derived retinal pigment epithelial (RPE) cell sheets to the eye of a patient with exudative age-related macular degeneration (AMD) in 2014 as a clinical research. Replacement of the RPE with the patient's own iPS cell-derived young healthy cell sheet will be one new radical treatment of AMD that is caused by cellular senescence of RPE cells. Since it was the first clinical study using iPS cell-derived cells, the primary endpoint was safety judged by the outcome one year after surgery. The safety of the cell sheet has been confirmed by repeated tumorigenisity tests using immunodeficient mice, as well as purity of the cells, karyotype and genetic analysis. It is, however, also necessary to prove the safety by clinical studies. Following this start, a good strategy considering cost and benefit is needed to make regenerative medicine a standard treatment in the future. Scientifically, the best choice is the autologous RPE cell sheet, but autologous cell are expensive and sheet transplantation involves a risky part of surgical procedure. We should consider human leukocyte antigen (HLA) matched allogeneic transplantation using the HLA 6 loci homozyous iPS cell stock that Prof. Yamanaka of Kyoto University is working on. As the required forms of donor cells will be different depending on types and stages of the target diseases, regenerative medicine will be accomplished in a totally different manner from the present small molecule drugs. Proof of concept (POC) of photoreceptor transplantation in mouse is close to being accomplished using iPS cell-derived photoreceptor cells. The shortest possible course for treatment

  19. Mesenchymal stem cell therapy and lung diseases.

    Science.gov (United States)

    Akram, Khondoker M; Samad, Sohel; Spiteri, Monica; Forsyth, Nicholas R

    2013-01-01

    Mesenchymal stem cells (MSCs), a distinct population of adult stem cells, have amassed significant interest from both medical and scientific communities. An inherent multipotent differentiation potential offers a cell therapy option for various diseases, including those of the musculoskeletal, neuronal, cardiovascular and pulmonary systems. MSCs also secrete an array of paracrine factors implicated in the mitigation of pathological conditions through anti-inflammatory, anti-apoptotic and immunomodulatory mechanisms. The safety and efficacy of MSCs in human application have been confirmed through small- and large-scale clinical trials. However, achieving the optimal clinical benefit from MSC-mediated regenerative therapy approaches is entirely dependent upon adequate understanding of their healing/regeneration mechanisms and selection of appropriate clinical conditions. MSC-mediated acute alveolar injury repair. A cartoon depiction of an injured alveolus with associated inflammation and AEC apoptosis. Proposed routes of MSC delivery into injured alveoli could be by either intratracheal or intravenous routes, for instance. Following delivery a proposed mechanism of MSC action is to inhibit/reduce alveolar inflammation by abrogation of IL-1_-depenedent Tlymphocyte proliferation and suppression of TNF-_ secretion via macrophage activation following on from stimulation by MSC-secreted IL-1 receptor antagonist (IL-1RN). The inflammatory environment also stimulates MSC to secrete prostaglandin-E2 (PGE2) which can stimulate activated macrophages to secrete the anti-inflammatory cytokine IL-10. Inhibition of AEC apoptosis following injury can also be promoted via MSC stimulated up-regulation of the anti-apoptotic Bcl-2 gene. MSC-secreted KGF can stimulate AECII proliferation and migration propagating alveolar epithelial restitution. Alveolar structural engraftment of MSC is a rare event. PMID:22772131

  20. COMPARISON OF ANTERIOR CHAMBER REACTION WITH SINGLE-PIECE AND THREE-PIECE INTRAOCULAR LENSES IN MANUAL SMALL INCISION CATARACT SURGERY

    Directory of Open Access Journals (Sweden)

    Usha

    2014-11-01

    Full Text Available OBJECTIVES: To study the anterior chamber reaction between single-piece and three-piece intraocular lenses in manual small incision cataract surgery. METHODS: Prospective study done at Mysore Race Club Charitable Eye Hospital. 140 Patients underwent suture less sclerocorneal tunnel cataract surgeries with single-piece or three-piece Polymethylmethacrylate (PMMA intra ocular lenses (3-piece IOL. Accurate Keratometry was done with the help of Bausch and Lomb Keratometer. IOL power was calculated by using SRK (Sanders-Retzlaff-Kraff II formula, with the help of non-immersion, contact type of A-Scan biometry. Single-piece IOLs were inserted in 70 patients. Three-piece IOL inserted in rest of 70 patients. Slit lamp examination for anterior chamber cells was graded according to Hogan system. Aqueous cells were measured by counting within the visible field under Slit lamp, keeping the beam at maximum intensity. Anterior chamber reaction (AC in 1stPostoperative week and at 8 weeks are compared and analyzed by ANOVA statistics. RESULTS: Single piece IOL group had anterior chamber reaction ranging from 1 to 2+ cells i.e., in 97%. In three-piece IOL group, 70%of eyes had 2+ cells and 12.8% had 3± cells. At 8 weeks, single- piece IOL showed either no cells or occasional cells in 98.6% of patients, compared to three –piece IOL group showing in 77%of cases. 23% had 1+ cells in later group. CONCLUSION: Single-piece implanted IOLs had significant less number of cells were seen in anterior chamber from 1 week to 8 weeks as compared to three-piece IOLs.

  1. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  2. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  3. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  4. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker

    2014-05-01

    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  5. CELL THERAPY FOR INTERVERTEBRAL DISC REPAIR: ADVANCING CELL THERAPY FROM BENCH TO CLINICS

    Science.gov (United States)

    Benneker, L.M.; Andersson, G.; Iatridis, J.C.; Sakai, D.; Härtl, R.; Ito, K.; Grad, S.

    2016-01-01

    Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects. PMID:24802611

  6. Stem Cell Therapy: A New Treatment for Burns?

    OpenAIRE

    Gauglitz, Gerd G.; Marc G. Jeschke; Mohammed Al Shehab; Anna Arno; Blit, Patrick H.; Smith, Alexandra H.

    2011-01-01

    Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells) or artificially obtained (induced pluripotent stem cells or iPSCs) and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, ...

  7. Recent advances in cell-based therapy for Parkinson disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Cooper, Oliver; Vinuela, Angel;

    2008-01-01

    In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression...... in enrichment and purification strategies of stem cell-derived dopaminergic midbrain neurons. They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease....

  8. Low Reactive Level Laser Therapy for Mesenchymal Stromal Cells Therapies

    OpenAIRE

    Toshihiro Kushibiki; Takeshi Hirasawa; Shinpei Okawa; Miya Ishihara

    2015-01-01

    Low reactive level laser therapy (LLLT) is mainly focused on the activation of intracellular or extracellular chromophore and the initiation of cellular signaling by using low power lasers. Over the past forty years, it was realized that the laser therapy had the potential to improve wound healing and reduce pain and inflammation. In recent years, the term LLLT has become widely recognized in the field of regenerative medicine. In this review, we will describe the mechanisms of action of LLLT...

  9. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  10. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  11. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

  12. Cell therapy in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.

  13. Mesenchymal stem cell therapy for heart disease.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Cervio, Elisabetta

    2012-08-19

    Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vascular cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and may greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. In this review we will focus on the current understanding of MSC biology and MSC mechanism of action in cardiac repair. PMID:22521741

  14. Nanomedicine-mediated cancer stem cell therapy.

    Science.gov (United States)

    Shen, Song; Xia, Jin-Xing; Wang, Jun

    2016-01-01

    Circumstantial evidence suggests that most tumours are heterogeneous and contain a small population of cancer stem cells (CSCs) that exhibit distinctive self-renewal, proliferation and differentiation capabilities, which are believed to play a crucial role in tumour progression, drug resistance, recurrence and metastasis in multiple malignancies. Given that the existence of CSCs is a primary obstacle to cancer therapy, a tremendous amount of effort has been put into the development of anti-CSC strategies, and several potential approaches to kill therapeutically-resistant CSCs have been explored, including inhibiting ATP-binding cassette transporters, blocking essential signalling pathways involved in self-renewal and survival of CSCs, targeting CSCs surface markers and destroying the tumour microenvironment. Meanwhile, an increasing number of therapeutic agents (e.g. small molecule drugs, nucleic acids and antibodies) to selectively target CSCs have been screened or proposed in recent years. Drug delivery technology-based approaches hold great potential for tackling the limitations impeding clinical applications of CSC-specific agents, such as poor water solubility, short circulation time and inconsistent stability. Properly designed nanocarrier-based therapeutic agents (or nanomedicines) offer new possibilities of penetrating CSC niches and significantly increasing therapeutic drug accumulation in CSCs, which are difficult for free drug counterparts. In addition, intelligent nanomedicine holds great promise to overcome pump-mediated multidrug resistance which is driven by ATP and to decrease detrimental effects on normal somatic stem cells. In this review, we summarise the distinctive biological processes related to CSCs to highlight strategies against inherently drug-resistant CSCs. We then focus on some representative examples that give a glimpse into state-of-the-art nanomedicine approaches developed for CSCs elimination. A perspective on innovative therapeutic

  15. Towards stem-cell therapy in the endocrine pancreas

    NARCIS (Netherlands)

    Gangaram-Panday, Shanti T.; Faas, Marijke M.; de Vos, Paul

    2007-01-01

    Many approaches of stem-cell therapy for the treatment of diabetes have been described. One is the application of stem cells for replacement of nonfunctional islet cells in the native endogenous pancreas; another one is the use of stem cells as an inexhaustible source for islet-cell transplantation.

  16. Application of Nanoscaffolds in Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Ghoraishizadeh, Saman; Ghorishizadeh, Afsoon; Ghoraishizadeh, Peyman; Daneshvar, Nasibeh; Boroojerdi, Mohadese Hashem

    2014-01-01

    Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling whi...

  17. MS Stem Cell Therapy Succeeds but Poses Risks

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159285.html MS Stem Cell Therapy Succeeds But Poses Risks Toxic side effects ... HealthDay News) -- A treatment combining chemotherapy and a stem cell transplant could represent a major advance against aggressive ...

  18. Cell Targeting in Anti-Cancer Gene Therapy

    OpenAIRE

    Lila, Mohd Azmi Mohd; Siew, John Shia Kwong; Zakaria, Hayati; Saad, Suria Mohd; Ni, Lim Shen; Abdullah, Jafri Malin

    2004-01-01

    Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene th...

  19. Development of gene and stem cell therapy for ocular neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Jing-Xue; Zhang; Ning-Li; Wang; Qing-Jun; Lu

    2015-01-01

    Retinal degenerative diseases pose a serious threat to eye health, but there is currently no effective treatment available. Recent years have witnessed rapid development of several cutting-edge technologies, such as gene therapy, stem cell therapy, and tissue engineering. Due to the special features of ocular structure, some of these technologies have been translated into ophthalmological clinic practice with fruitful achievements, setting a good example for other fields. This paper reviews the development of the gene and stem cell therapies in ophthalmology.

  20. Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

    NARCIS (Netherlands)

    K.W. ter Horst

    2010-01-01

    The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by

  1. Personalized Therapy of Small Cell Lung Cancer.

    Science.gov (United States)

    Schneider, Bryan J; Kalemkerian, Gregory P

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials. PMID:26703804

  2. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  3. Potential benefits of cell therapy in coronary heart disease.

    Science.gov (United States)

    Grimaldi, Vincenzo; Mancini, Francesco Paolo; Casamassimi, Amelia; Al-Omran, Mohammed; Zullo, Alberto; Infante, Teresa; Napoli, Claudio

    2013-11-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the world. In recent years, there has been an increasing interest both in basic and clinical research regarding the field of cell therapy for coronary heart disease (CHD). Several preclinical models of CHD have suggested that regenerative properties of stem and progenitor cells might help restoring myocardial functions in the event of cardiac diseases. Here, we summarize different types of stem/progenitor cells that have been tested in experimental and clinical settings of cardiac regeneration, from embryonic stem cells to induced pluripotent stem cells. Then, we provide a comprehensive description of the most common cell delivery strategies with their major pros and cons and underline the potential of tissue engineering and injectable matrices to address the crucial issue of restoring the three-dimensional structure of the injured myocardial region. Due to the encouraging results from preclinical models, the number of clinical trials with cell therapy is continuously increasing and includes patients with CHD and congestive heart failure. Most of the already published trials have demonstrated safety and feasibility of cell therapies in these clinical conditions. Several studies have also suggested that cell therapy results in improved clinical outcomes. Numerous ongoing clinical trials utilizing this therapy for CHD will address fundamental issues concerning cell source and population utilized, as well as the use of imaging techniques to assess cell homing and survival, all factors that affect the efficacy of different cell therapy strategies. PMID:23834957

  4. Potential benefits of cell therapy in coronary heart disease.

    Science.gov (United States)

    Grimaldi, Vincenzo; Mancini, Francesco Paolo; Casamassimi, Amelia; Al-Omran, Mohammed; Zullo, Alberto; Infante, Teresa; Napoli, Claudio

    2013-11-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the world. In recent years, there has been an increasing interest both in basic and clinical research regarding the field of cell therapy for coronary heart disease (CHD). Several preclinical models of CHD have suggested that regenerative properties of stem and progenitor cells might help restoring myocardial functions in the event of cardiac diseases. Here, we summarize different types of stem/progenitor cells that have been tested in experimental and clinical settings of cardiac regeneration, from embryonic stem cells to induced pluripotent stem cells. Then, we provide a comprehensive description of the most common cell delivery strategies with their major pros and cons and underline the potential of tissue engineering and injectable matrices to address the crucial issue of restoring the three-dimensional structure of the injured myocardial region. Due to the encouraging results from preclinical models, the number of clinical trials with cell therapy is continuously increasing and includes patients with CHD and congestive heart failure. Most of the already published trials have demonstrated safety and feasibility of cell therapies in these clinical conditions. Several studies have also suggested that cell therapy results in improved clinical outcomes. Numerous ongoing clinical trials utilizing this therapy for CHD will address fundamental issues concerning cell source and population utilized, as well as the use of imaging techniques to assess cell homing and survival, all factors that affect the efficacy of different cell therapy strategies.

  5. Dental stem cells: a future asset of ocular cell therapy.

    Science.gov (United States)

    Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Singhal, Shweta; Goh, Bee-Tin; Mehta, Jodhbir S

    2015-11-10

    Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine.

  6. Cell therapy to remove excess copper in Wilson's disease.

    Science.gov (United States)

    Gupta, Sanjeev

    2014-05-01

    To achieve permanent correction of Wilson's disease by a cell therapy approach, replacement of diseased hepatocytes with healthy hepatocytes is desirable. There is a physiological requirement for hepatic ATP7B-dependent copper (Cu) transport in bile, which is deficient in Wilson's disease, producing progressive Cu accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raises the possibility of cell therapy in Wilson's disease. Therapeutic principles included reconstitution of bile canalicular network as well as proliferation in transplanted hepatocytes, despite toxic amounts of Cu in the liver. Nonetheless, cell therapy studies in animal models elicited major differences in the mechanisms driving liver repopulation with transplanted hepatocytes in Wilson's disease versus nondiseased settings. Recently, noninvasive imaging was developed to demonstrate Cu removal from the liver, including after cell therapy in Wilson's disease. Such developments will help advance cell/gene therapy approaches, particularly by offering roadmaps for clinical trials in people with Wilson's disease.

  7. Stem cell therapy in oral and maxillofacial region: An overview

    Directory of Open Access Journals (Sweden)

    P M Sunil

    2012-01-01

    Full Text Available Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects.

  8. Three-dimensional approach to stem cell therapy.

    OpenAIRE

    Oh, Il-Hoan; Kim, Dong-Wook

    2002-01-01

    Recent progress in stem cell research is opening a new hope for cell therapy in regenerative medicine. Two breakthroughs were made in the stem cell era, one, new discoveries in multi-potentiality of adult stem cells beyond the traditionally appreciated extent, and the other, establishment of pluripotent stem cell from human embryo. In addition to the newly identified multi-potentiality of adult stem cells, their ability to be trans-differentiated toward other tissue types (stem cell plasticit...

  9. Stem cell-based therapy for erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    WU Jian-hong; XIA Shu-jie

    2011-01-01

    Objective To review the effect of stem cells in erectile dysfunction as well as their application to the therapy of erectile dysfunction.Data sources The data used in the present article were mainly from PubMed with relevant English articles published from 1974 to 2011.The search terms were "stem cells" and "erectile dysfunction".Study selection Articles regarding the role of stem cells in erectile dysfunction and their application to the therapy of erectile dysfunction were selected.Results Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types.Meanwhile,in preclinical experiments,therapeutic gene-modified stem cells have been approved to offer a novel strategy for cell therapy and gene therapy of erectile dysfunction.Conclusion The transplantation of stem cells has the potential to provide cell types capable of restoring normal function after injury or degradation inerectile dysfunction.However,a series of problems,such as the safety of stem cells transplantation,their application in cell therapy and gene therapy of erectile dysfunction need further investigation.

  10. Multiple piece turbine rotor blade

    Energy Technology Data Exchange (ETDEWEB)

    Kimmel, Keith D.; Plank, William L.

    2016-07-19

    A spar and shell turbine rotor blade with a spar and a tip cap formed as a single piece, the spar includes a bottom end with dovetail or fir tree slots that engage with slots on a top end of a root section, and a platform includes an opening on a top surface for insertion of the spar in which a shell made from an exotic high temperature resistant material is secured between the tip cap and the platform. The spar is tapered to form thinner walls at the tip end to further reduce the weight and therefore a pulling force due to blade rotation. The spar and tip cap piece is made from a NiAL material to further reduce the weight and the pulling force.

  11. 1.A piece of cake

    Institute of Scientific and Technical Information of China (English)

    吕浙

    2005-01-01

    对西方人来说,蛋糕是极其平常的食物。无论是做蛋糕还是吃蛋糕.都是轻松愉快的一桩小事,因此,a piece of cake这个习语的意思是“非常简单,易如反掌.小菜一碟”。如:

  12. Cell-based therapies and imaging in cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Bengel, Frank M. [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Munich (Germany); Schachinger, Volker; Dimmeler, Stefanie [University of Frankfurt, Department of Molecular Cardiology, Frankfurt (Germany)

    2005-12-01

    Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application. (orig.)

  13. Chimeric Antigen Receptor T Cell Therapy in Hematology.

    Science.gov (United States)

    Ataca, Pınar; Arslan, Önder

    2015-12-01

    It is well demonstrated that the immune system can control and eliminate cancer cells. Immune-mediated elimination of tumor cells has been discovered and is the basis of both cancer vaccines and cellular therapies including hematopoietic stem cell transplantation. Adoptive T cell transfer has been improved to be more specific and potent and to cause less off-target toxicity. Currently, there are two forms of engineered T cells being tested in clinical trials: T cell receptor (TCR) and chimeric antigen receptor (CAR) modified T cells. On 1 July 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to anti-CD19 CAR T cell therapy. Many studies were conducted to evaluate the benefits of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical and clinical studies, and the effectiveness and drawbacks of this strategy.

  14. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  15. Advances in sickle cell therapies in the hydroxyurea era.

    Science.gov (United States)

    Field, Joshua J; Nathan, David G

    2014-01-01

    In the hydroxyurea era, insights into mechanisms downstream of erythrocyte sickling have led to new therapeutic approaches for patients with sickle cell disease (SCD). Therapies have been developed that target vascular adhesion, inflammation and hemolysis, including innovative biologics directed against P-selectin and invariant natural killer T cells. Advances in hematopoietic stem cell transplant and gene therapy may also provide more opportunities for cures in the near future. Several clinical studies are underway to determine the safety and efficacy of these new treatments. Novel approaches to treat SCD are desperately needed, since current therapies are limited and rates of morbidity and mortality remain high. PMID:25549232

  16. Stem cell therapy in treatment of different diseases.

    Science.gov (United States)

    Larijani, Bagher; Esfahani, Ensieh Nasli; Amini, Peyvand; Nikbin, Behrouz; Alimoghaddam, Kamran; Amiri, Somayeh; Malekzadeh, Reza; Yazdi, Nika Mojahed; Ghodsi, Maryam; Dowlati, Yahya; Sahraian, Mohammad Ali; Ghavamzadeh, Ardeshir

    2012-01-01

    Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia). In this paper the goal is evaluation of cell therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.

  17. Stem Cell Therapy in Treatment of Different Diseases

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sahraian

    2012-02-01

    Full Text Available Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia. In this paper the goal is evaluation of cell therapy in treatment of Parkinsons disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.

  18. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.;

    2009-01-01

    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

  19. Stem-cell-based therapy and lessons from the heart.

    NARCIS (Netherlands)

    Passier, R.; van Laake, L.W.; Mummery, C.L.

    2008-01-01

    The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alte

  20. Apoptosis and cancer stem cells : Implications for apoptosis targeted therapy

    NARCIS (Netherlands)

    Kruyt, Frank A. E.; Schuringa, Jan Jacob

    2010-01-01

    Evidence is accumulating showing that cancer stem cells or tumor-initiating cells are key drivers of tumor formation and progression. Successful therapy must therefore eliminate these cells, which is hampered by their high resistance to commonly used treatment modalities. Thus far, only a limited nu

  1. Cell therapy strategies and improvements for muscular dystrophy

    OpenAIRE

    Quattrocelli, Mattia; Cassano, Marco; Crippa, Stefania; Perini, Ilaria; Sampaolesi, Maurilio

    2010-01-01

    Understanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this rev...

  2. Cell therapy for liver diseases: current medicine and future promises.

    Science.gov (United States)

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  3. Human embryonic stem cell therapies for neurodegenerative diseases.

    Science.gov (United States)

    Tomaskovic-Crook, Eva; Crook, Jeremy M

    2011-06-01

    There is a renewed enthusiasm for the clinical translation of human embryonic stem (hES) cells. This is abetted by putative clinically-compliant strategies for hES cell maintenance and directed differentiation, greater understanding of and accessibility to cells through formal cell registries and centralized cell banking for distribution, the revised US government policy on funding hES cell research, and paradoxically the discovery of induced pluripotent stem (iPS) cells. Additionally, as we consider the constraints (practical and fiscal) of delivering cell therapies for global healthcare, the more efficient and economical application of allogeneic vs autologous treatments will bolster the clinical entry of hES cell derivatives. Neurodegenerative disorders such as Parkinson's disease are primary candidates for hES cell therapy, although there are significant hurdles to be overcome. The present review considers key advances and challenges to translating hES cells into novel therapies for neurodegenerative diseases, with special consideration given to Parkinson's disease and Alzheimer's disease. Importantly, despite the focus on degenerative brain disorders and hES cells, many of the issues canvassed by this review are relevant to systemic application of hES cells and other pluripotent stem cells such as iPS cells.

  4. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  5. Slow-Cycling Therapy-Resistant Cancer Cells

    OpenAIRE

    Moore, Nathan; Houghton, JeanMarie; Lyle, Stephen

    2011-01-01

    Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be secondary to small subsets of cancer cells that are better able to survive traditional forms of chemotherapy and thus drive tumor regrowth. The ability to isolate and better characterize these therapy-resistant cells is critical for the future development of targeted therapies aimed at achieving more robust and long-lasting responses. Using a novel application for the prolife...

  6. Stem Cell Based Gene Therapy in Prostate Cancer

    OpenAIRE

    Jae Heon Kim; Hong Jun Lee; Yun Seob Song

    2014-01-01

    Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new ...

  7. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

    OpenAIRE

    Gabriel eGonzales-Portillo; Stephanny eReyes; Daniela eAguirre; Pabon, Mibel M.; Borlongan, Cesar V.

    2014-01-01

    Treatments for neonatal hypoxic-ischemic encephalopathy (HIE) have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with str...

  8. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Gabriel eGonzales-Portillo

    2014-08-01

    Full Text Available Treatments for neonatal hypoxic ischemic encephalopathy (HIE have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke providing insights on the potential of cell therapy, currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS, which have been recently modified to Baby STEPS to cater for the neonatal symptoms of HIE. These guidelines recognized that neonatal HIE exhibits distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials, and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE.

  9. Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Masaya Nakamura; Hideyuki Okano

    2013-01-01

    Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon,there is an increasing interest in the induced pluripotent stem (iPS) cells and reprograming technologies in medical science.While iPS cells are expected to open a new era providing enormous opportunities in biomedical sciences in terms of cell therapies and regenerative medicine,safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells.In this review,the pre-clinical investigations of cell therapy for spinal cord injury (SCI) using neural stem/progenitor cells derived from iPS cells,and their safety issues in vivo,are outlined.We also wish to discuss the strategy for the first human trails of iPS cell-based cell therapy for SCI patients.

  10. The translational imperative: Making cell therapy simple and effective ☆

    Science.gov (United States)

    Prestwich, Glenn D.; Erickson, Isaac E.; Zarembinski, Thomas I.; West, Michael; Tew, William P.

    2012-01-01

    The current practice of cell therapy, in which multipotent or terminally differentiated cells are injected into tissues or intravenously, is inefficient. Few therapeutic cells are retained at the site of administration and engraftment is low. An injectable and biologically appropriate vehicle for delivery, retention, growth and differentiation of therapeutic cells is needed to improve the efficacy of cell therapy. We focus on a hyaluronan-based semi-synthetic extracellular matrix (sECM), HyStem®, which is a manufacturable, approvable and affordable clinical product. The composition of this sECM can be customized for use with mesenchymal stem cells as well as cells derived from embryonic or induced pluripotent sources. In addition, it can support therapeutic uses of progenitor and mature cell populations obtained from skin, fat, liver, heart, muscle, bone, cartilage, nerves and other tissues. This overview presents four pre-clinical uses of HyStem® for cell therapy to repair injured vocal folds, improve post-myocardial infarct heart function, regenerate damaged liver tissue and restore brain function following ischemic stroke. Finally, we address the real-world limitations – manufacture, regulation, market acceptance and financing – surrounding cell therapy and the development of clinical combination products. PMID:22776825

  11. The translational imperative: making cell therapy simple and effective.

    Science.gov (United States)

    Prestwich, Glenn D; Erickson, Isaac E; Zarembinski, Thomas I; West, Michael; Tew, William P

    2012-12-01

    The current practice of cell therapy, in which multipotent or terminally differentiated cells are injected into tissues or intravenously, is inefficient. Few therapeutic cells are retained at the site of administration and engraftment is low. An injectable and biologically appropriate vehicle for delivery, retention, growth and differentiation of therapeutic cells is needed to improve the efficacy of cell therapy. We focus on a hyaluronan-based semi-synthetic extracellular matrix (sECM), HyStem®, which is a manufacturable, approvable and affordable clinical product. The composition of this sECM can be customized for use with mesenchymal stem cells as well as cells derived from embryonic or induced pluripotent sources. In addition, it can support therapeutic uses of progenitor and mature cell populations obtained from skin, fat, liver, heart, muscle, bone, cartilage, nerves and other tissues. This overview presents four pre-clinical uses of HyStem® for cell therapy to repair injured vocal folds, improve post-myocardial infarct heart function, regenerate damaged liver tissue and restore brain function following ischemic stroke. Finally, we address the real-world limitations - manufacture, regulation, market acceptance and financing - surrounding cell therapy and the development of clinical combination products. PMID:22776825

  12. [Novelties in the diagnostics and therapy of hairy cell leukemia].

    Science.gov (United States)

    Sári, Eszter; Rajnai, Hajnalka; Dénes, Kitti; Bödör, Csaba; Csomor, Judit; Körösmezey, Gábor; Tárkányi, Ilona; Eid, Hanna; Nagy, Zsolt; Demeter, Judit

    2016-06-01

    Differential diagnosis of hairy cell leukemia (HCL) and related disorders (hairy cell leukemia variant and splenic marginal zone lymphoma) is of utmost importance since the treatment and prognosis of these lymphomas differ. Since 2011 diagnosis of hairy cell leukemia has been easier because of discovery of the disease defining somatic mutation BRAF V600E mutation, which has been also known as driver mutation in malignant melanoma. The presence of this mutation enabled targeted molecular therapy in HCL as well. As first line therapy purine nucleoside analogues are the gold standard, but refractory/relapsed patient are candidates for targeted BRAF-inhibitor therapy. This manuscript serves as guidance in making diagnosis and standard treatment of HCL, and summarizes newest data about molecular therapy, including our single center experience collected from 75 patients. PMID:27275640

  13. Cancer stem cells: therapeutic implications and perspectives in cancer therapy

    Directory of Open Access Journals (Sweden)

    Lu Han

    2013-04-01

    Full Text Available The cancer stem cell (CSC theory is gaining increasing attention from researchers and has become an important focus of cancer research. According to the theory, a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny, termed cancer stem cells (CSCs. Understanding the properties and characteristics of CSCs is key to future study on cancer research, such as the isolation and identification of CSCs, the cancer diagnosis, and the cancer therapy. Standard oncology treatments, such as chemotherapy, radiotherapy and surgical resection, can only shrink the bulk tumor and the tumor tends to relapse. Thus, therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffectiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance. The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.

  14. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet ,; Lange, Kenneth

    2009-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tool...

  15. [Systemic therapy of metastatic renal cell carcinoma].

    Science.gov (United States)

    Maute, Luise; Bergmann, Lothar

    2016-04-01

    In metastatic ccRCC , the treatment options in 1st line treatment are still the tyrosinkinase inhibitors (TKI) pazopanib and sunitinib, for patients with low or intermediate risk additionally IFNα/bevacizumab and for high risk patients the mTOR inhibitor temsirolimus. In 2nd line following cytokine therapy, axitinib or pazopanib and following TKI /VEGF directed therapy axitinib or everolimus may be administered. New upcoming agents in RCC are the PD1 antibody nivolumab and the multikinase inhibitor Cabozantinib, which both showed an OS advantage compared to everolimus. After marketing authorization in Europe, these agents should therefore be preferred in 2nd and 3rd line therapy. Further agents are under investigation. PMID:27031198

  16. Cell therapy using induced pluripotent stem cells or somatic stem cells: this is the question.

    Science.gov (United States)

    Somoza, Rodrigo A; Rubio, Francisco J

    2012-05-01

    A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS.

  17. RETAINED STONE PIECE IN ANTERIOR CHAMBER

    Directory of Open Access Journals (Sweden)

    ZvornicaninJasmin, Nadarevic-VodencarevicAmra

    2015-04-01

    Full Text Available ABSTRACT We read with interest the article by Surekha et al. regarding the retained stone piece in anterior chamber. Similar to the results of previous studies, the authors found that delayed intraocular foreign body (IOFB management can result in good visual outcome without an apparent increased risk of endophthalmitis or other deleterious side effects. However, the authors failed to explain the exact reason for the diminution of vision in patients left eye. It is unclear what the uncorrected visual acuity was and what kind of correction was used, more precisely type and amount of cylinder, given the presence of the corneal opacity. Since the size of the IOFB is approximately 4x4x1mm, significant irido-corneal angle changes resulting in intraocular pressure raise and optic nerve head damage can be expected. Traumatic glaucoma following open globe injury can occur in 2.7 to 19% of cases, with several risk factors associated with glaucoma development (advanced age, poor visual acuity at presentation,perforating rather than penetrating ocular injury,lens injury, presence of vitreous hemorrhage and presence of an IOFB. Earlier reportsof latetraumaticoptic neuropathy onset, even after several years, indicate that this possibility cannot be completely ruled out too. Therefore, repeated intraocular pressure measurements, gonioscopy, pupillary reaction assessment, together with through posterior segment examination including visual field and optical coherence tomography examinations can be useful in determining the possible optic nerve damage as one of the possible reasons for visual acuity reduction. The authors did not suggest any operative treatment at this time. However, it should bear in mind that the inert anterior chamber IOFB could be a risk factor for non-infectious endophthalmitis development even after many years. Also, long term retained anterior chamber foreign body leads to permanent endothelial cell loss and can even result in a corneal

  18. Methods for Stem Cell Production and Therapy

    Science.gov (United States)

    Claudio, Pier Paolo (Inventor); Valluri, Jagan V. (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  19. Stem Cell-Based Therapies for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lei Hao

    2014-01-01

    Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

  20. The Use of Pluripotent Stem Cell for Personalized Cell Therapies against Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Hye-Yeong Ha

    2011-01-01

    Full Text Available Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.

  1. Proceedings: international regulatory considerations on development pathways for cell therapies.

    Science.gov (United States)

    Feigal, Ellen G; Tsokas, Katherine; Viswanathan, Sowmya; Zhang, Jiwen; Priest, Catherine; Pearce, Jonathan; Mount, Natalie

    2014-08-01

    Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field's development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses.

  2. Stem cells therapy in cerebral palsy: A systematic review.

    Science.gov (United States)

    Kułak-Bejda, Agnieszka; Kułak, Piotr; Bejda, Grzegorz; Krajewska-Kułak, Elżbieta; Kułak, Wojciech

    2016-09-01

    The aim of this study was to systematically present the best available stem cell therapies for children with cerebral palsy (CP). The databases Medline, PubMed, EMBASE, and the Cochrane Controlled Trials Register for RCTs were searched for studies published from 1967 to August 2015. Systematic reviews, randomised controlled trials (RCTs), controlled trials, uncontrolled trials, cohort studies, open-label studies, and a meta-analysis were analysed. Of 360 articles, seven fulfilled the inclusion criteria: one RCT and six were open-label trials. In these studies, one application of stem cells for children with CP was typical, and the total number of cells administered to patients ranged from 10(6) to 10(8)/kg. Different routes of cell delivery were used, though in most studies motor development was applied as an indicator of primary outcomes. In three articles, neuroimaging studies were also implemented to confirm the efficacy of the therapies. Observation periods varied from 3months to 5years, and patients' tolerance of the therapy was generally good. Stem cell therapy may improve some symptoms in patients with CP, though larger studies are needed to examine the impact of stem cell therapy upon CP. PMID:27004672

  3. Regulatory landscape for cell therapy--EU view.

    Science.gov (United States)

    McBlane, James W

    2015-09-01

    This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial. A regulation is soon to come into force that will address this and introduce a more efficient clinical trial application process. However, at the marketing authorisation stage, the process is pan-national: the Committee for Human Medicinal Products (CHMP) is responsible for giving the final scientific opinion on all EU marketing authorisation applications for cell therapies: favourable scientific opinions are passed to the European Commission (EC) for further consultation and, if successful, grant of a marketing authorisation valid in all 28 EU countries. In its review of applications for marketing authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the Committee for Advanced Therapies (CAT), who conduct detailed scientific assessments of these applications, with assessment by staff from national regulatory authorities and specialist advisors to the regulators. PMID:25997566

  4. Stem Cell Therapy in Pediatric Neurological Disorders

    OpenAIRE

    Farnaz Torabian; Arvin Aghayi Nejad; Arash Akhavan Rezayat; Mehran Beiraghi Toosi; Ali Reza Attaei Nakhaie; Hamid Reza Rahimi

    2015-01-01

    Pediatric neurological disorders including muscular dystrophy, cerebral palsy, and spinal cord injury are defined as a heterogenous group of diseases, of which some are known to be genetic. The two significant features represented for stem cells, leading to distinguish them from other cell types are addressed as below: they can renew themselves besides the ability to differentiate into cells with special function as their potency. Researches about the role of stem cells in repair of damaged t...

  5. Bone marrow cells differentiation into organ cells using stem cell therapy.

    Science.gov (United States)

    Yang, Y-J; Li, X-L; Xue, Y; Zhang, C-X; Wang, Y; Hu, X; Dai, Q

    2016-07-01

    Bone marrow cells (BMC) are progenitors of bone, cartilage, skeletal tissue, the hematopoiesis-supporting stroma and adipocyte cells. BMCs have the potential to differentiate into neural cells, cardiac myocytes, liver hepatocytes, chondrocytes, renal, corneal, blood, and myogenic cells. The bone marrow cell cultures from stromal and mesenchymal cells are called multipotent adult progenitor cells (MAPCs). MAPCs can differentiate into mesenchymal cells, visceral mesoderm, neuroectoderm and endoderm in vitro. It has been shown that the stem cells derived from bone marrow cells (BMCs) can regenerate cardiac myocytes after myocardial infarction (MI). Adult bone marrow mesenchymal stem cells have the ability to regenerate neural cells. Neural stem/progenitor cells (NS/PC) are ideal for treating central nervous system (CNS) diseases, such as Alzheimer's, Parkinson's and Huntington disease. However, there are important ethical issues about the therapeutic use of stem cells. Neurons, cardiac myocytes, hepatocytes, renal cells, blood cells, chondrocytes and adipocytes regeneration from BMCs are very important in disease control. It is known that limbal epithelial stem cells in the cornea can repair the eye sight and remove symptoms of blindness. Stem cell therapy (SCT) is progressing well in animal models, but the use of SCT in human remains to be explored further.

  6. Ethical issues in stem cell research and therapy.

    Science.gov (United States)

    King, Nancy Mp; Perrin, Jacob

    2014-07-07

    Rapid progress in biotechnology has introduced a host of pressing ethical and policy issues pertaining to stem cell research. In this review, we provide an overview of the most significant issues with which the stem cell research community should be familiar. We draw on a sample of the bioethics and scientific literatures to address issues that are specific to stem cell research and therapy, as well as issues that are important for stem cell research and therapy but also for translational research in related fields, and issues that apply to all clinical research and therapy. Although debate about the moral status of the embryo in human embryonic stem cell research continues to have relevance, the discovery of other highly multipotent stem cell types and alternative methods of isolating and creating highly multipotent stem cells has raised new questions and concerns. Induced pluripotent stem cells hold great promise, but care is needed to ensure their safety in translational clinical trials, despite the temptation to move quickly from bench to bedside. A variety of highly multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from amniotic fluid, umbilical cord blood, adipose tissue, or urine - present the opportunity for widespread biobanking and increased access. With these increased opportunities, however, come pressing policy issues of consent, control, and justice. The imperatives to minimize risks of harm, obtain informed consent, reduce the likelihood of the therapeutic misconception, and facilitate sound translation from bench to bedside are not unique to stem cell research; their application to stem cell research and therapy nonetheless merits particular attention. Because stem cell research is both scientifically promising and ethically challenging, both the application of existing ethical frameworks and careful consideration of new ethical implications are necessary as this broad and diverse field moves forward.

  7. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  8. Towards Personalized Regenerative Cell Therapy: Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2016-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing the importance of choosing the right sources of iPSCs, iPSC reprogramming methods, iPSC culture systems, embryoid body intermediates, pathway inhibitors, basal medium, serum, growth factors and culture surface coating. We also highlight some progress in the application of iPSC-MSCs in direct cell therapy, tissue engineering and gene therapy.

  9. [Maintenance therapy for advanced non-small-cell lung cancer].

    Science.gov (United States)

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  10. Progress toward cell-directed therapy for phenylketonuria.

    Science.gov (United States)

    Harding, Co

    2008-08-01

    Phenylketonuria (PKU) is one of the most common inborn errors of metabolism with an annual incidence of approximately 1:16,000 live births in North America. Contemporary therapy relies upon lifelong dietary protein restriction and supplementation with phenylalanine-free medical foods. This therapy is expensive and unpalatable; dietary compliance is difficult to maintain throughout life. Non-adherence to the diet is associated with learning disabilities, adult-onset neurodegenerative disease, and maternal PKU syndrome. The fervent dream of many individuals with PKU is a more permanent cure for this disease. This paper will review ongoing efforts to develop viable cell-directed therapies, in particular cell transplantation and gene therapy, for the treatment of PKU. PMID:18498375

  11. Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mauricio P. Pinto

    2016-09-01

    Full Text Available Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1 upregulation of compensatory/alternative pathways for angiogenesis; (2 vasculogenic mimicry; and (3 vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

  12. Stem cell research: paths to cancer therapies and regenerative medicine.

    Science.gov (United States)

    Weissman, Irving

    2005-09-21

    Most tissues in complex metazoans contain a rare subset of cells that, at the single-cell level, can self-renew and also give rise to mature daughter cells. Such stem cells likely in development build tissues and are retained in adult life to regenerate them. Cancers and leukemias are apparently not an exception: rare leukemia stem cells and cancer stem cells have been isolated that contain all of the tumorigenicity of the whole tumor, and it is their properties that will guide future therapies. None of this was apparent just 20 years ago, yet this kind of stem cell thinking already provides new perspectives in medical science and could usher in new therapies. Today, political, religious, and ethical issues surround embryonic stem cell and patient-specific pluripotent stem cell research and are center stage in the attempts by governments to ban these fields for discovery and potential therapies. These interventions require physicians and physician-scientists to determine for themselves whether patient welfare or personal ethics will dominate in their practices, and whether all aspects of stem cell research can be pursued in a safe and regulated fashion.

  13. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Nagwa El-Badri

    2013-01-01

    Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

  14. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  15. Development of gene and stem cell therapy for ocular neurodegeneration

    OpenAIRE

    Zhang, Jing-Xue; Wang, Ning-Li; Lu, Qing-Jun

    2015-01-01

    Retinal degenerative diseases pose a serious threat to eye health, but there is currently no effective treatment available. Recent years have witnessed rapid development of several cutting-edge technologies, such as gene therapy, stem cell therapy, and tissue engineering. Due to the special features of ocular structure, some of these technologies have been translated into ophthalmological clinic practice with fruitful achievements, setting a good example for other fields. This paper reviews t...

  16. Stem Cell Therapy to Treat Diabetes Mellitus

    OpenAIRE

    Liew, Chee Gee; Andrews, Peter W.

    2008-01-01

    Transplantation of pancreatic islets offers a direct treatment for type 1 diabetes and in some cases, insulin-dependent type 2 diabetes. However, its widespread use is hampered by a shortage of donor organs. Many extant studies have focused on deriving β-cell progenitors from pancreas and pluripotent stem cells. Efforts to generate β-cells in vitro will help elucidate the mechanisms of β-cell formation and thus provide a versatile in vivo system to evaluate the therapeutic potential of these ...

  17. Lineage-specific reprogramming as a strategy for cell therapy.

    Science.gov (United States)

    Darabi, Radbod; Perlingeiro, Rita C R

    2008-06-15

    Embryonic stem (ES) cells are endowed with extensive ability for self renewal and differentiation. These features make them a promising candidate for cell therapy. However, despite the enthusiasm and hype surrounding the potential therapeutic use of human ES cells and more recently induced pluripotent stem (iPS) cells, to date few reports have documented successful therapeutic outcome with ES-derived cell populations. This is probably due to two main caveats associated with ES cells, their capacity to form teratomas and the challenge of isolating the appropriate therapeutic cell population from differentiating ES cells. We have focused our efforts on the derivation of skeletal muscle progenitors from ES cells and here we will discuss the strategy of reprogramming lineage choices by overexpression of a master regulator, which has proven successful for the generation of the skeletal myogenic lineage from mouse ES cells.

  18. The Alpha Stem Cell Clinic: a model for evaluating and delivering stem cell-based therapies.

    Science.gov (United States)

    Trounson, Alan; DeWitt, Natalie D; Feigal, Ellen G

    2012-01-01

    Cellular therapies require the careful preparation, expansion, characterization, and delivery of cells in a clinical environment. There are major challenges associated with the delivery of cell therapies and high costs that will limit the companies available to fully evaluate their merit in clinical trials, and will handicap their application at the present financial environment. Cells will be manufactured in good manufacturing practice or near-equivalent facilities with prerequisite safety practices in place, and cell delivery systems will be specialized and require well-trained medical and nursing staff, technicians or nurses trained to handle cells once delivered, patient counselors, as well as statisticians and database managers who will oversee the monitoring of patients in relatively long-term follow-up studies. The model proposed for Alpha Stem Cell Clinics will initially use the capacities and infrastructure that exist in the most advanced tertiary medical clinics for delivery of established bone marrow stem cell therapies. As the research evolves, they will incorporate improved procedures and cell preparations. This model enables commercialization of medical devices, reagents, and other products required for cell therapies. A carefully constructed cell therapy clinical infrastructure with the requisite scientific, technical, and medical expertise and operational efficiencies will have the capabilities to address three fundamental and critical functions: 1) fostering clinical trials; 2) evaluating and establishing safe and effective therapies, and 3) developing and maintaining the delivery of therapies approved by the Food and Drug Administration, or other regulatory agencies.

  19. Emerging Stem Cell Therapies: Treatment, Safety, and Biology

    Directory of Open Access Journals (Sweden)

    Joel Sng

    2012-01-01

    Full Text Available Stem cells are the fundamental building blocks of life and contribute to the genesis and development of all higher organisms. The discovery of adult stem cells has led to an ongoing revolution of therapeutic and regenerative medicine and the proposal of novel therapies for previously terminal conditions. Hematopoietic stem cell transplantation was the first example of a successful stem cell therapy and is widely utilized for treating various diseases including adult T-cell leukemia-lymphoma and multiple myeloma. The autologous transplantation of mesenchymal stem cells is increasingly employed to catalyze the repair of mesenchymal tissue and others, including the lung and heart, and utilized in treating various conditions such as stroke, multiple sclerosis, and diabetes. There is also increasing interest in the therapeutic potential of other adult stem cells such as neural, mammary, intestinal, inner ear, and testicular stem cells. The discovery of induced pluripotent stem cells has led to an improved understanding of the underlying epigenetic keys of pluripotency and carcinogenesis. More in-depth studies of these epigenetic differences and the physiological changes that they effect will lead to the design of safer and more targeted therapies.

  20. Stem Cell Therapy: A New Treatment for Burns?

    Directory of Open Access Journals (Sweden)

    Gerd G. Gauglitz

    2011-10-01

    Full Text Available Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells or artificially obtained (induced pluripotent stem cells or iPSCs and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, but also as an adjunct to other strategies, such as organ transplantation or standard drug treatment. Regrettably, serious preclinical concerns remain and differentiation, cell fusion, senescence and signalling crosstalk with growth factors and biomaterials are still challenges for this promising multidisciplinary therapeutic modality. Severe burns have several indications for stem cell therapy, including enhancement of wound healing, replacement of damaged skin and perfect skin regeneration – incorporating skin appendages and reduced fibrosis –, as well as systemic effects, such as inflammation, hypermetabolism and immunosuppression. The aim of this review is to describe well established characteristics of stem cells and to delineate new advances in the stem cell field, in the context of burn injury and wound healing.

  1. Dynamic imaging for CAR-T-cell therapy.

    Science.gov (United States)

    Emami-Shahri, Nia; Papa, Sophie

    2016-04-15

    Chimaeric antigen receptor (CAR) therapy is entering the mainstream for the treatment of CD19(+)cancers. As is does we learn more about resistance to therapy and the role, risks and management of toxicity. In solid tumour CAR therapy research the route to the clinic is less smooth with a wealth of challenges facing translating this, potentially hugely valuable, therapeutic option for patients. As we strive to understand our successes, and navigate the challenges, having a clear understanding of how adoptively transferred CAR-T-cells behavein vivoand in human trials is invaluable. Harnessing reporter gene imaging to enable detection and tracking of small numbers of CAR-T-cells after adoptive transfer is one way by which we can accomplish this. The compatibility of certain reporter gene systems with tracers available routinely in the clinic makes this approach highly useful for future appraisal of CAR-T-cell success in humans. PMID:27068944

  2. Nanoelectroablation therapy for murine basal cell carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. ► Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. ► Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. ► Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1+/−K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5–7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm3 shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  3. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  4. Modeling of gene therapy for regenerative cells using intelligent agents.

    Science.gov (United States)

    Adly, Aya Sedky; Aboutabl, Amal Elsayed; Ibrahim, M Shaarawy

    2011-01-01

    Gene therapy is an exciting field that has attracted much interest since the first submission of clinical trials. Preliminary results were very encouraging and prompted many investigators and researchers. However, the ability of stem cells to differentiate into specific cell types holds immense potential for therapeutic use in gene therapy. Realization of this potential depends on efficient and optimized protocols for genetic manipulation of stem cells. It is widely recognized that gain/loss of function approaches using gene therapy are essential for understanding specific genes functions, and such approaches would be particularly valuable in studies involving stem cells. A significant complexity is that the development stage of vectors and their variety are still not sufficient to be efficiently applied in stem cell therapy. The development of scalable computer systems constitutes one step toward understanding dynamics of its potential. Therefore, the primary goal of this work is to develop a computer model that will support investigations of virus' behavior and organization on regenerative tissues including genetically modified stem cells. Different simulation scenarios were implemented, and their results were encouraging compared to ex vivo experiments, where the error rate lies in the range of acceptable values in this domain of application.

  5. Reassessing target antigens for adoptive T cell therapy

    Science.gov (United States)

    Hinrichs, Christian S.; Restifo, Nicholas P.

    2014-01-01

    Adoptive T cell therapy can target and kill widespread malignant cells thereby inducing durable clinical responses in melanoma and selected other malignances. However, many commonly targeted tumor antigens are also expressed by healthy tissues, and T cells do not distinguish between benign and malignant tissues if both express the target antigen. As such, autoimmune toxicity from T-cell-mediated destruction of normal tissue has limited the development and adoption of this otherwise promising type of cancer therapy. A review of the unique biology of T-cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities. In selecting target antigens for adoptive T-cell therapy, expression by tumors and not by essential healthy tissues is of paramount importance. The risk of autoimmune adverse events can be further mitigated by generating antigen receptors using strategies that reduce the chance of cross-reactivity against epitopes in unintended targets. In general, a circumspect approach to target selection and thoughtful preclinical and clinical studies are pivotal to the ongoing advancement of these promising treatments. PMID:24142051

  6. Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Arjen F. Nikkels

    2010-06-01

    Full Text Available Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methyl-aminolevulinate (MAL based photodynamic therapy (PDT resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence. Although spontaneous regression of cutaneous Langerhans cell histiocytosis is observed, the rapid effect of photodynamic therapy after several failures of other treatment suggests that photodynamic therapy was successful. As far as we know this is the first report of photodynamic therapy for refractory skin lesions. Larger series are needed to determine whether photodynamic therapy deserves a place in the treatment of multiresistant cutaneous Langerhans cell histiocytosis.

  7. Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury

    Science.gov (United States)

    Zickri, Maha Baligh; Zaghloul, Somaya; Farouk, Mira; Fattah, Marwa Mohamed Abdel

    2012-01-01

    Background and Objectives It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. Methods and Results Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. Conclusions ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy. PMID:24298366

  8. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Sk Md Fazle Akbar; Norio Horiike; Morikazu Onji

    2006-01-01

    Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses.However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult.During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective.A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

  9. Gene Profiling Technique to Accelerate Stem Cell Therapies for Eye Diseases

    Science.gov (United States)

    ... to accelerate stem cell therapies for eye diseases Gene profiling technique to accelerate stem cell therapies for ... The method simultaneously measures the expression of multiple genes, allowing scientists to quickly characterize cells according to ...

  10. PET molecular imaging in stem cell therapy for neurological diseases

    International Nuclear Information System (INIS)

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  11. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  12. Anti-B cell antibody therapies for inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Jayne, David R W

    2014-01-01

    Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, polymyositis/dermatomyositis, and primary Sjögren's syndrome. For some anti-B cell agents, clinical benefits have been convincingly demonstrated, while other B cell-targeted therapies failed to improve outcomes when added to standard...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

  13. Mesenchymal stem cell therapy for acute radiation syndrome.

    Science.gov (United States)

    Fukumoto, Risaku

    2016-01-01

    Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation, such as that caused by detonation of nuclear devices and inappropriate medical treatments. Therefore, there is a growing need for medical interventions that facilitate the improved recovery of victims and patients. One promising approach may be cell therapy, which, when appropriately implemented, may facilitate recovery from whole body injuries. This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome, the benefits and limitations of which are under investigation. Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches. PMID:27182446

  14. Stem cells - biological update and cell therapy progress

    OpenAIRE

    GIRLOVANU, MIHAI; Susman, Sergiu; Soritau, Olga; RUS-CIUCA, DAN; MELINCOVICI, CARMEN; CONSTANTIN, ANNE-MARIE; Carmen Mihaela MIHU

    2015-01-01

    In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods t...

  15. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    Science.gov (United States)

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  16. Gene and stem cell therapy in peripheral arterial occlusive disease.

    Science.gov (United States)

    Kalka, C; Baumgartner, Iris

    2008-01-01

    Peripheral arterial occlusive disease (PAOD) is a manifestation of systemic atherosclerosis strongly associated with a high risk of cardiovascular morbidity and mortality. In a considerable proportion of patients with PAOD, revascularization either by endovascular means or by open surgery combined with best possible risk factor modification does not achieve limb salvage or relief of ischaemic rest pain. As a consequence, novel therapeutic strategies have been developed over the last two decades aiming to promote neovascularization and remodelling of collaterals. Gene and stem cell therapy are the main directions for clinical investigation concepts. For both, preclinical studies have shown promising results using a wide variety of genes encoding for growth factors and populations of adult stem cells, respectively. As a consequence, clinical trials have been performed applying gene and stem cell-based concepts. However, it has become apparent that a straightforward translation into humans is not possible. While several trials reported relief of symptoms and functional improvement, other trials did not confirm this early promise of efficacy. Ongoing clinical trials with an improved study design are needed to confirm the potential that gene and cell therapy may have and to prevent the gaps in our scientific knowledge that will jeopardize the establishment of angiogenic therapy as an additional medical treatment of PAOD. This review summarizes the experimental background and presents the current status of clinical applications and future perspectives of the therapeutic use of gene and cell therapy strategies for PAOD.

  17. On dendritic cell-based therapy for cancers

    Institute of Scientific and Technical Information of China (English)

    Morikazu Onji; Sk. Md. Fazle Akbar

    2005-01-01

    Dendritic cells (DCs), the most prevalent antigen-presenting cell in vivo, had been widely characterized in the last three decades. DCs are present in almost all tissues of the body and play cardinal roles in recognition of microbial agents,autoantigens, allergens and alloantigen. DCs process the microbial agents or their antigens and migrate to lymphoid tissues to present the antigenic peptide to lymphocytes. This leads to activation of antigen-specific lymphocytes. Initially, it was assumed that DCs are principally involved in the induction and maintenance of adaptive immune responses, but now it is evident that DCs also have important roles in innate immunity. These features make DCs very good candidates for therapy against various pathological conditions including malignancies. Initially, DC-based therapy was used in animal models of cancers. Data from these studies inspired considerable optimism and DC-based therapies was started in human cancers 8 years ago. In general,DC-based therapy has been found to be safe in patients with cancers, although few controlled trials have been conducted in this regard. Because the fundamentals principles of human cancers and animal models of cancers are different, the therapeutic efficacy of the ongoing regime of DC-based therapy in cancer patients is not satisfactory. In this review, we covered the various aspects that should be considered for developing better regime of DC-based therapy for human cancers.

  18. FORIDA Towers - Analysis of steel transition piece

    DEFF Research Database (Denmark)

    Jensen, Lars Rom; Dollerup, Niels; Damkilde, Lars

    This report is a detailed analysis of the transition piece connecting the hybrid wind turbine towers lower UHPFRC part with the top steel part. The analysis of the transition piece includes a validation of the Service Limit State (SLS), the Ultimate Limit State (ULS) and the Fatigue loads. The...

  19. Stem Cell Therapy for Treatment of Ocular Disorders.

    Science.gov (United States)

    Sivan, Padma Priya; Syed, Sakinah; Mok, Pooi-Ling; Higuchi, Akon; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Awang Hamat, Rukman; Umezawa, Akihiro; Kumar, Suresh

    2016-01-01

    Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  20. Stem Cell Therapy for Treatment of Ocular Disorders

    Directory of Open Access Journals (Sweden)

    Padma Priya Sivan

    2016-01-01

    Full Text Available Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  1. Effects of Photodynamic Therapy on the Ultrastructure of Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. Methods The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. Results Apoptosis in different phases and necrosis could be observed in some C6 glioma cells.Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells.Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile,limited impact on the normal sub-cellular structures and BBB was observed. Conclusion PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

  2. Advances in stem cell therapy for cardiovascular disease (Review).

    Science.gov (United States)

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  3. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    Diabetes mellitus is a well-known risk factor for coronary artery disease (CAD), which can lead to acute myocardial infarction, chronic myocardial ischaemia and heart failure. Despite the advantages in medical treatment, percutaneous coronary intervention (PCI) and coronary artery bypass grafting...... of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared...

  4. Cardiac stem cell therapy research in China

    Institute of Scientific and Technical Information of China (English)

    Junbo GE

    2006-01-01

    @@ For more than two decades, the morbidity and mortality of coronary artery disease (CAD) has been increasing rapidly in China. Despite tremendous advances in treatment strategies of CAD, heart failure after acute myocardial infarction (AMI) continues to be one of the greatest medical challenges throughout the world. In 1994, Soonpaa and colleagues first reported the possibility of cardiomyocytes implantation and suggested that intracardiac cell grafting might provide a useful approach for myocardial repair.1 Cell implantation has become a novel therapeutic option for ischemic cardiac injury and heart failure.

  5. Embryonic stem cells: prospects for developmental biology and cell therapy.

    Science.gov (United States)

    Wobus, Anna M; Boheler, Kenneth R

    2005-04-01

    Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation.

  6. Monoclonal T-cell receptors: new reagents for cancer therapy.

    Science.gov (United States)

    Stauss, Hans J; Cesco-Gaspere, Michela; Thomas, Sharyn; Hart, Daniel P; Xue, Shao-An; Holler, Angelika; Wright, Graham; Perro, Mario; Little, Ann-Margaret; Pospori, Constantina; King, Judy; Morris, Emma C

    2007-10-01

    Adoptive transfer of antigen-specific T lymphocytes is an effective form of immunotherapy for persistent virus infections and cancer. A major limitation of adoptive therapy is the inability to isolate antigen-specific T lymphocytes reproducibly. The demonstration that cloned T-cell receptor (TCR) genes can be used to produce T lymphocyte populations of desired specificity offers new opportunities for antigen-specific T-cell therapy. TCR gene-modified lymphocytes display antigen-specific function in vitro, and were shown to protect against virus infection and tumor growth in animal models. A recent trial in humans demonstrated that TCR gene-modified T cells persisted in all and reduced melanoma burden in 2/15 patients. In future trials, it may be possible to use TCR gene transfer to equip helper and cytotoxic T cells with new antigen-specificity, allowing both T-cell subsets to cooperate in achieving improved clinical responses. Sequence modifications of TCR genes are being explored to enhance TCR surface expression, while minimizing the risk of pairing between introduced and endogenous TCR chains. Current T-cell transduction protocols that trigger T-cell differentiation need to be modified to generate "undifferentiated" T cells, which, upon adoptive transfer, display improved in vivo expansion and survival. Both, expression of only the introduced TCR chains and the production of naïve T cells may be possible in the future by TCR gene transfer into stem cells. PMID:17637721

  7. Cell Internal Treatable Microplasma Jets in Cancer Therapies

    Science.gov (United States)

    Kim, Jae Young; Wei, Yanzhang; Li, Jinhua; Kim, Sung-O.

    2011-10-01

    We developed a 15- μm-sized, single-cellular-level, and cell-manipulatable microplasma jet device with a microcapillary glass tip and described its potential in physical cancer therapies. The microcapillary tip is a funnel shaped glass tube and its nozzle has an inner diameter of 15 μm and an outer diameter of 20 μm with 20 capillary angle. The electrical and optical properties of this plasma jet and apoptosis results of cultured murine B16F0 melanoma tumor cells and CL.7 fibroblast cells treated with the plasma jets were described. In spite of the small inner diameter and the low gas flow rate of the microplasma jet device, the generated plasma jets are stable enough to treat tumor cells. The microplasma jet was observed inducing apoptosis in cultured murine melanoma tumor cells in a dose-dependent manner. Furthermore, the percentage of apoptotic cells of murine melanoma tumor cells induced by this plasma device was approximately 2.5 times bigger than that of murine fibroblast cells as indicated by an Annex V-FITC method. This highly precise plasma medicine, which enables new directed cancer therapies, can be combined with current cell manipulation and cell culturing technologies without much difficulty.

  8. Gene and stem cell therapy of the hair follicle.

    Science.gov (United States)

    Hoffman, Robert M

    2005-01-01

    The hair follicle is a highly complex appendage of the skin containing a multiplicity of cell types. The follicle undergoes constant cycling through the life of the organism including growth and resorption with growth dependent on specific stem cells. The targeting of the follicle by genes and stem cells to change its properties, in particular, the nature of the hair shaft is discussed. Hair follicle delivery systems are described such as liposomes and viral vectors for gene therapy. The nature of the hair follicle stem cells is discussed, in particular, its pluripotency.

  9. Novel Therapies for Aggressive B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Kenneth A. Foon

    2012-01-01

    Full Text Available Aggressive B-cell lymphoma (BCL comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL, Burkitt lymphoma, and mantle cell lymphoma (MCL. DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper.

  10. Gene, Stem Cell, and Alternative Therapies for SCA 1

    Science.gov (United States)

    Wagner, Jacob L.; O'Connor, Deirdre M.; Donsante, Anthony; Boulis, Nicholas M.

    2016-01-01

    Spinocerebellar ataxia 1 is an autosomal dominant disease characterized by neurodegeneration and motor dysfunction. In disease pathogenesis, polyglutamine expansion within Ataxin-1, a gene involved in transcriptional repression, causes protein nuclear inclusions to form. Most notably, neuronal dysfunction presents in Purkinje cells. However, the effect of mutant Ataxin-1 is not entirely understood. Two mouse models are employed to represent spinocerebellar ataxia 1, a B05 transgenic model that specifically expresses mutant Ataxin-1 in Purkinje cells, and a Sca1 154Q/2Q model that inserts the polyglutamine expansion into the mouse Ataxin-1 locus so that the mutant Ataxin-1 is expressed in all cells that express Ataxin-1. This review aims to summarize and evaluate the wide variety of therapies proposed for spinocerebellar ataxia 1, specifically gene and stem cell therapies.

  11. iPS-cell derived dendritic cells and macrophages for cancer therapy.

    Science.gov (United States)

    Senju, Satoru

    2016-08-01

    Antibody-based anti-cancer immunotherapy was recently recognized as one of the truly effective therapies for cancer patients. Antibodies against cell surface cancer antigens, such as CD20, and also those against immune-inhibitory molecules called "immune checkpoint blockers", such as CTLA4 or PD1, have emerged. Large-scale clinical trials have confirmed that, in some cases, antibody-based drugs are superior to conventional chemotherapeutic agents. These antibody-based drugs are now being manufactured employing a mass-production system by pharmaceutical companies. Anti-cancer therapy by immune cells, i.e. cell-based immunotherapy, is expected to be more effective than antibody therapy, because immune cells can recognize, infiltrate, and act in cancer tissues more directly than antibodies. In order to achieve cell-based anti-cancer immunotherapy, it is necessary to develop manufacturing systems for mass-production of immune cells. Our group has been studying immunotherapy with myeloid cells derived from ES cells or iPS cells. These pluripotent stem cells can be readily propagated under constant culture conditions, with expansion into a large quantity. We consider these stem cells to be the most suitable cellular source for mass-production of immune cells. This review introduces our studies on anti-cancer therapy with iPS cell-derived dendritic cells and iPS cell-derived macrophages. PMID:27599426

  12. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies

    OpenAIRE

    Shi, Yanhong

    2009-01-01

    Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties. Recent breakthrough studies using a combination of four factors to reprogram human somatic cells into pluripotent stem cells without using embryos or eggs led to an important revolution in stem cell research. Comparative analysis of human induced pluripotent stem cells and human embryonic stem cel...

  13. Eliminating Cancer Stem Cells in CML with Combination Transcriptional Therapy.

    Science.gov (United States)

    Carvajal, Luis A; Steidl, Ulrich

    2016-07-01

    Leukemia stem cells (LSCs) are resistant to current therapies used to treat chronic myeloid leukemia (CML). Abraham et al. (2016) have identified a molecular network critical for CML LSC survival and propose that simultaneously targeting two of their major transcriptional regulators, p53 and c-Myc, may facilitate their eradication. PMID:27392220

  14. Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    2014-01-01

    textabstractAfter more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme

  15. Understanding the application of stem cell therapy in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Sharma RK

    2012-10-01

    Full Text Available Rakesh K Sharma, Donald J Voelker, Roma Sharma, Hanumanth K ReddyUniversity of Arkansas for Medical Sciences, Medical Center of South Arkansas, El Dorado, AR, USAAbstract: Throughout their lifetime, an individual may sustain many injuries and recover spontaneously over a period of time, without even realizing the injury in the first place. Wound healing occurs due to a proliferation of stem cells capable of restoring the injured tissue. The ability of adult stem cells to repair tissue is dependent upon the intrinsic ability of tissues to proliferate. The amazing capacity of embryonic stem cells to give rise to virtually any type of tissue has intensified the search for similar cell lineage in adults to treat various diseases including cardiovascular diseases. The ability to convert adult stem cells into pluripotent cells that resemble embryonic cells, and to transplant those in the desired organ for regenerative therapy is very attractive, and may offer the possibility of treating harmful disease-causing mutations. The race is on to find the best cells for treatment of cardiovascular disease. There is a need for the ideal stem cell, delivery strategies, myocardial retention, and time of administration in the ideal patient population. There are multiple modes of stem cell delivery to the heart with different cell retention rates that vary depending upon method and site of injection, such as intra coronary, intramyocardial or via coronary sinus. While there are crucial issues such as retention of stem cells, microvascular plugging, biodistribution, homing to myocardium, and various proapoptotic factors in the ischemic myocardium, the regenerative potential of stem cells offers an enormous impact on clinical applications in the management of cardiovascular diseases.Keywords: stem cell therapy, stem cell delivery, cardiovascular diseases, myocardial infarction, cardiomyopathy

  16. [Current cell therapy strategies for repairing the central nervous system].

    Science.gov (United States)

    Féron, F

    2007-09-01

    One of the chief contemporary goals of neurologists and neuroscientists is to find a way to overcome the debilitating effects of brain diseases, especially neurodegenerative diseases. Since very few molecules have been found to be efficient in curing the patients and even halting the progression of the symptoms, cell therapy is now seen as an attractive alternative. Two therapeutic strategies are currently under investigation: i) the "substitution" strategy, based on grafts of cells capable of differentiating in the appropriate cells and restoring lost functions and ii) the "neuroprotective" or "conservative" strategy aiming to increase the resistance of spared cells to the toxicity of their environment and to reinforce the body's own mechanisms of healing. Twenty years ago, foetal neuroblasts were the first cells to be transplanted in the brains of patients with Parkinson's or Huntington disease. A phase II clinical trial is presently conducted in France for the latter disorder. However, the numerous ethical and technical issues raised by the use of embryonic and foetal cells have directed the focus of clinicians and researchers towards substitute cell types. In this review, we summarise the main findings of the most recent basic studies and clinical trials based on: i) the grafting of surrogate adult cells such as bone marrow mesenchymal stem cells and olfactory ensheathing cells; ii) the potential therapeutic applications of neuropoiesis - the persistent neurogenesis in the brain - as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells and iii) immune-based therapy (autologous activated macrophages and T cell vaccination) as well as administration of immunomodulatory molecules. Unexpectedly, it has been found that undifferentiated adult stem cells can display immune-like functions when they home in on an inflamed brain area while immune cells and immunosuppressors can improve functional and

  17. Systemic adjuvant therapies in renal cell carcinoma

    OpenAIRE

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  18. Stem cell-based therapy in neural repair.

    Science.gov (United States)

    Hsu, Yi-Chao; Chen, Su-Liang; Wang, Dan-Yen; Chiu, Ing-Ming

    2013-01-01

    Cell-based therapy could aid in alleviating symptoms or even reversing the progression of neurodegenerative diseases and nerve injuries. Fibroblast growth factor 1 (FGF1) has been shown to maintain the survival of neurons and induce neurite outgrowth. Accumulating evidence suggests that combination of FGF1 and cell-based therapy is promising for future therapeutic application. Neural stem cells (NSCs), with the characteristics of self-renewal and multipotency, can be isolated from embryonic stem cells, embryonic ectoderm, and developing or adult brain tissues. For NSC clinical application, several critical problems remain to be resolved: (1) the source of NSCs should be personalized; (2) the isolation methods and protocols of human NSCs should be standardized; (3) the clinical efficacy of NSC transplants must be evaluated in more adequate animal models; and (4) the mechanism of intrinsic brain repair needs to be better characterized. In addition, the ideal imaging technique for tracking NSCs would be safe and yield high temporal and spatial resolution, good sensitivity and specificity. Here, we discuss recent progress and future development of cell-based therapy, such as NSCs, induced pluripotent stem cells, and induced neurons, in neurodegenerative diseases and peripheral nerve injuries. PMID:23806879

  19. CAR T Cell Therapy: A Game Changer in Cancer Treatment.

    Science.gov (United States)

    Almåsbak, Hilde; Aarvak, Tanja; Vemuri, Mohan C

    2016-01-01

    The development of novel targeted therapies with acceptable safety profiles is critical to successful cancer outcomes with better survival rates. Immunotherapy offers promising opportunities with the potential to induce sustained remissions in patients with refractory disease. Recent dramatic clinical responses in trials with gene modified T cells expressing chimeric antigen receptors (CARs) in B-cell malignancies have generated great enthusiasm. This therapy might pave the way for a potential paradigm shift in the way we treat refractory or relapsed cancers. CARs are genetically engineered receptors that combine the specific binding domains from a tumor targeting antibody with T cell signaling domains to allow specifically targeted antibody redirected T cell activation. Despite current successes in hematological cancers, we are only in the beginning of exploring the powerful potential of CAR redirected T cells in the control and elimination of resistant, metastatic, or recurrent nonhematological cancers. This review discusses the application of the CAR T cell therapy, its challenges, and strategies for successful clinical and commercial translation. PMID:27298832

  20. Myocardium repair with stem cell therapy

    International Nuclear Information System (INIS)

    With the aim of assessing the efficacy of bone marrow-derived stem cells transplantation in patients with myocardial infarction and severe chronic heart failure through nuclear cardiology techniques, 15 revascularized patients were studied: nine (Group I) received autologous bone marrow-derived stem cells. The other six were controls (Group II). All underwent a clinical evaluation, radionuclide ventriculography, and gated-SPECT myocardial perfusion scintigraphy (MIBI-technetium99m, two-day protocol: dipyridamole - rest), before and three months after the procedure. At three months there was a clinical improvement in 89% of patients from Group I. The left ventricular ejection fraction increased: from 32±9% to 44±13% (p=0.03; Group I) and from 38±2% to 48±14% (p NS; Group II). The peak filling rate improved from 120±11 to 196±45 EDV/sec (p=0.03; Group I). The dipyridamole summed score diminished significantly only in Group I (from 35±5 to 23±14; p=0.02). The perfusion improvement was related to the implantation site in 60% of cases. We conclude that the bone marrow-derived stem cells transplantation is effective in patients with severe chronic heart failure of ischemic origin (au)

  1. Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications.

    Science.gov (United States)

    Kuo, Tom K; Ho, Jennifer H; Lee, Oscar K

    2009-01-01

    Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases. PMID:19523328

  2. Effects of verteporfin-mediated photodynamic therapy on endothelial cells

    Science.gov (United States)

    Kraus, Daniel; Chen, Bin

    2015-03-01

    Photodynamic therapy (PDT) is a treatment modality in which cytotoxic reactive oxygen species are generated from oxygen and other biological molecules when a photosensitizer is activated by light. PDT has been approved for the treatment of cancers and age-related macular degeneration (AMD) due to its effectiveness in cell killing and manageable normal tissue complications. In this study, we characterized the effects of verteporfin-PDT on SVEC mouse endothelial cells and determined its underlying cell death mechanisms. We found that verteporfin was primarily localized in mitochondria and endoplasmic reticulum (ER) in SVEC cells. Light treatment of photosensitized SVEC cells induced a rapid onset of cell apoptosis. In addition to significant structural damages to mitochondria and ER, verteporfin-PDT caused substantial degradation of ER signaling molecules, suggesting ER stress. These results demonstrate that verteporfin-PDT triggered SVEC cell apoptosis by both mitochondrial and ER stress pathways. Results from this study may lead to novel therapeutic approaches to enhance PDT outcome.

  3. Stem cell-based therapies for HIV/AIDS.

    Science.gov (United States)

    Pernet, Olivier; Yadav, Swati Seth; An, Dong Sung

    2016-08-01

    One of the current focuses in HIV/AIDS research is to develop a novel therapeutic strategy that can provide a life-long remission of HIV/AIDS without daily drug treatment and, ultimately, a cure for HIV/AIDS. Hematopoietic stem cell-based anti-HIV gene therapy aims to reconstitute the patient immune system by transplantation of genetically engineered hematopoietic stem cells with anti-HIV genes. Hematopoietic stem cells can self-renew, proliferate and differentiate into mature immune cells. In theory, anti-HIV gene-modified hematopoietic stem cells can continuously provide HIV-resistant immune cells throughout the life of a patient. Therefore, hematopoietic stem cell-based anti-HIV gene therapy has a great potential to provide a life-long remission of HIV/AIDS by a single treatment. Here, we provide a comprehensive review of the recent progress of developing anti-HIV genes, genetic modification of hematopoietic stem progenitor cells, engraftment and reconstitution of anti-HIV gene-modified immune cells, HIV inhibition in in vitro and in vivo animal models, and in human clinical trials. PMID:27151309

  4. Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

    Directory of Open Access Journals (Sweden)

    Janis eAncans

    2012-08-01

    Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

  5. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  6. Key developments in stem cell therapy in cardiology.

    Science.gov (United States)

    Schulman, Ivonne H; Hare, Joshua M

    2012-11-01

    A novel therapeutic strategy to prevent or reverse ventricular remodeling, the substrate for heart failure and arrhythmias following a myocardial infarction, is the use of cell-based therapy. Successful cell-based tissue regeneration involves a complex orchestration of cellular and molecular events that include stem cell engraftment and differentiation, secretion of anti-inflammatory and angiogenic mediators, and proliferation of endogenous cardiac stem cells. Recent therapeutic approaches involve bone marrow-derived mononuclear cells and mesenchymal stem cells, adipose tissue-derived stem cells, cardiac-derived stem cells and cell combinations. Clinical trials employing mesenchymal stem cells and cardiac- derived stem cells have demonstrated efficacy in infarct size reduction and regional wall contractility improvement. Regarding delivery methods, the safety of catheter-based, transendocardial stem cell injection has been established. These proof-of-concept studies have paved the way for ongoing pivotal trials. Future studies will focus on determining the most efficacious cell type(s) and/or cell combinations and the mechanisms underlying their therapeutic effects.

  7. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  8. From cell signaling to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jin DING; Yun FENG; Hong-yang WANG

    2007-01-01

    Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood.Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key mol-ecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec),herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects.

  9. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H

    1998-01-01

    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...... with initial versus delayed radiotherapy. No survival differences in the larger study of the two studies were detected, which compared alternating with sequential delivery of radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be defined. Two small, randomized studies on dose intensity...

  10. Stem cells and regenerative therapies for Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Farrell K

    2012-07-01

    Full Text Available Krista Farrell, Roger A BarkerCambridge Centre for Brain Repair, University of Cambridge, Cambridge, UKAbstract: Currently the mainstay of Parkinson’s disease (PD therapy is the pharmacological replacement of the loss of the dopaminergic nigrostriatal pathway using drugs such as dopamine agonists and levodopa. Whilst these drugs effectively ameliorate some of the motor features of PD, they do not improve many of the nonmotor features that arise secondary to pathology outside of this system, nor do they slow the progressive neurodegeneration that is a characteristic of the disease. Regenerative therapies for PD seek to fill this therapeutic gap, with cell transplantation being the most explored approach to date. A number of different cell sources have been used in this therapeutic approach, but to date, the most successful has been the use of fetal ventral mesencephalic (VM tissue that contains within it the developing nigral dopaminergic cells. Cell transplantation for PD was pioneered in the 1980–1990s, with several successful open-label trials of fetal VM transplantation in patients with relatively advanced PD. Whilst these findings were not replicated in two subsequent double-blind sham-surgery controlled trials, there were reasons to explain this outside of the one drawn at the time that these therapies are ineffective. Indeed all these studies have provided evidence that following the transplantation of fetal VM tissue, dopaminergic cells can survive long term, produce dopamine, and bring about clinical improvements in younger patients over many years. The use of fetal tissue, irrespective of its true efficacy, will never become a widely available therapy for PD for a host of practical and ethical reasons, and thus much work has been put in recently to exploring the utility of stem cells as a source of nigral dopaminergic neurons. In this respect, the advent of embryonic stem cell and induced pluripotent cells has heralded a new era in

  11. Importance of the stem cell microenvironment forophthalmological cell-based therapy

    Institute of Scientific and Technical Information of China (English)

    Peng-Xia Wan; Bo-Wen Wang; Zhi-Chong Wang

    2015-01-01

    Cell therapy is a promising treatment for diseasesthat are caused by cell degeneration or death. Thecells for clinical transplantation are usually obtainedby culturing healthy allogeneic or exogenous tissue invitro . However, for diseases of the eye, obtaining theadequate number of cells for clinical transplantationis difficult due to the small size of tissue donors andthe frequent needs of long-term amplification ofcells in vitro , which results in low cell viability aftertransplantation. In addition, the transplanted cells oftendevelop fibrosis or degrade and have very low survival.Embryonic stem cells (ESCs) and induced pluripotentstem cells (iPS) are also promising candidates for celltherapy. Unfortunately, the differentiation of ESCs canbring immune rejection, tumorigenicity and undesireddifferentiated cells, limiting its clinical application.Although iPS cells can avoid the risk of immune rejectioncaused by ES cell differentiation post-transplantation,the low conversion rate, the risk of tumor formationand the potentially unpredictable biological changesthat could occur through genetic manipulation hinderits clinical application. Thus, the desired clinical effectof cell therapy is impaired by these factors. Recentresearch findings recognize that the reason for lowsurvival of the implanted cells not only depends on theseeded cells, but also on the cell microenvironment,which determines the cell survival, proliferation andeven reverse differentiation. When used for cell therapy,the transplanted cells need a specific three-dimensionalstructure to anchor and specific extra cellular matrixcomponents in addition to relevant cytokine signalingto transfer the required information to support theirgrowth. These structures present in the matrix inwhich the stem cells reside are known as the stem cellmicroenvironment. The microenvironment interactionwith the stem cells provides the necessary homeostasisfor cell maintenance and growth. A large number ofstudies

  12. Stem cell therapy in intracerebral hemorrhage rat model

    Institute of Scientific and Technical Information of China (English)

    Marcos F Cordeiro; Ana P Horn

    2015-01-01

    Intracerebral hemorrhage (ICH) is a very complexpathology, with many different not fully elucidatedetiologies and prognostics. It is the most severe subtypeof stroke, with high mortality and morbidity rates.Unfortunately, despite the numerous promising preclinicalassays including neuroprotective, anti-hypertensive,and anti-inflammatory drugs, to this moment onlysymptomatic treatments are available, motivating thesearch for new alternatives. In this context, stem celltherapy emerged as a promising tool. However, morethan a decade has passed, and there is still much to belearned not only about stem cells, but also about ICHitself, and how these two pieces come together. To date,rats have been the most widely used animal model inthis research field, and there is much more to be learnedfrom and about them. In this review, we first summarizeICH epidemiology, risk factors, and pathophysiology. Wethen present different methods utilized to induce ICHin rats, and examine how accurately they represent thehuman disease. Next, we discuss the different typesof stem cells used in previous ICH studies, also takinginto account the tested transplantation sites. Finally, wesummarize what has been achieved in assays with stemcells in rat models of ICH, and point out some relevantissues where attention must be given in future efforts.

  13. Last piece of ATLAS takes the plunge

    CERN Multimedia

    2008-01-01

    On Friday 29 February the second small wheel was lowered 100 metres underground into the ATLAS cavern in front of a captivated audience. Although called the "small wheels" they are small in name only - each wheel is 9.3 metres in diameter and weighs 100 tonnes including the massive shielding elements. This piece completes ATLAS’ muon spectrometer, which has the ability to accurately track particles to the width of a human hair. The first piece of ATLAS was installed in 2003 and, five years later, this small wheel is the final large piece of the detector to take the subterranean voyage to its final resting place.

  14. Mesenchymal stem cell-based therapy for type 1 diabetes.

    Science.gov (United States)

    Wu, Hao; Mahato, Ram I

    2014-03-01

    Diabetes has increasingly become a worldwide health problem, causing huge burden on healthcare system and economy. Type 1 diabetes (T1D), traditionally termed "juvenile diabetes" because of an early onset age, is affecting 5-10% of total diabetic population. Insulin injection, the predominant treatment for T1D, is effective to ameliorate the hyperglycemia but incompetent to relieve the autoimmunity and to regenerate lost islets. Islet transplantation, an experimental treatment for T1D, also suffers from limited supply of human islets and poor immunosuppression. The recent progress in regenerative medicine, especially stem cell therapy, has suggested several novel and potential cures for T1D. Mesenchymal stem cell (MSC) based cell therapy is among one of them. MSCs are a type of adult stem cells residing in bone marrow, adipose tissue, umbilical cord blood, and many other tissues. MSCs, with self-renewal potential and transdifferentiation capability, can be expanded in vitro and directed to various cell lineages with relatively less efforts. MSCs have well-characterized hypoimmunogenicity and immunomodulatory effect. All these features make MSCs attractive for treating T1D. Here, we review the properties of MSCs and some of the recent progress using MSCs as a new therapeutic in the treatment of T1D. We also discuss the strength and limitations of using MSC therapy in human trials.

  15. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    Science.gov (United States)

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy. PMID:25860803

  16. Gold nanocages for imaging and therapy of prostate cancer cells

    Science.gov (United States)

    Sironi, Laura; Avvakumova, Svetlana; Galbiati, Elisabetta; Locarno, Silvia A.; Macchi, Chiara; D'Alfonso, Laura; Ruscica, Massimiliano; Magni, Paolo; Collini, Maddalena; Romeo, Sergio; Chirico, Giuseppe; Prosperi, Davide

    2016-04-01

    Gold nanocages (AuNCs) have been shown to be a useful tool both for imaging and hyperthermia therapy of cancer, thanks to their outstanding optical properties, low toxicity and facile functionalization with targeting molecules, including peptides and antibodies. In particular, hyperthermia is a minimally invasive therapy which takes advantage of the peculiar properties of gold nanoparticles to efficiently convert the absorbed light into heat. Here, we use AuNCs for the selective targeting and imaging of prostate cancer cells. Moreover, we report the hyperthermic effect characterization of the AuNCs both in solution and internalized in cells. Prostate cancer cells were irradiated at different exposure times, with a pulsed near infrared laser, and the cellular viability was evaluated by confocal microscopy.

  17. Trimodal therapy in squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Matuschek C

    2011-10-01

    Full Text Available Abstract Patients with ESCC (squamous cell carcinoma of the esophagus are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.

  18. Mesenchymal stem cell therapy for osteoarthritis: current perspectives.

    Science.gov (United States)

    Wyles, Cody C; Houdek, Matthew T; Behfar, Atta; Sierra, Rafael J

    2015-01-01

    Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

  19. Stem cell therapy in the management of shoulder rotatorcuff disorders

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Rotator cuff tears are frequent shoulder problems thatare usually dealt with surgical repair. Despite improvedsurgical techniques, the tendon-to-bone healing rateis unsatisfactory due to difficulties in restoring thedelicate transitional tissue between bone and tendon.It is essential to understand the molecular mechanismsthat determine this failure. The study of the molecularenvironment during embryogenesis and during normalhealing after injury is key in devising strategies to geta successful repair. Mesenchymal stem cells (MSC) candifferentiate into different mesodermal tissues and havea strong paracrine, anti-inflammatory, immunoregulatoryand angiogenic potential. Stem cell therapy is thus apotentially effective therapy to enhance rotator cuffhealing. Promising results have been reported with theuse of autologous MSC of different origins in animalstudies they have shown to have better healing properties,increasing the amount of fibrocartilage formationand improving the orientation of fibrocartilage fibers withless immunologic response and reduced lymphocyteinfiltration. All these changes lead to an increase inbiomechanical strength. However, animal research is stillinconclusive and more experimental studies are neededbefore human application. Future directions includeexpanded stem cell therapy in combination with growthfactors or different scaffolds as well as new stem celltypes and gene therapy.

  20. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies.

  1. iPS cell therapy for Parkinson's disease.

    Science.gov (United States)

    Takahashi, Jun

    2016-08-01

    The aim of stem cell therapy for Parkinson's disease (PD) is to reconstruct local synapse formation and/or induce the release of dopamine and cytokines from grafted cells in the putamen. Fetal ventral-midbrain cells reportedly relieve the neurological symptoms of PD patients. However, induced pluripotent stem cells (iPSCs) are expected to provide an alternative donor cell population because of their capacity for self-renewal and pluripotency. A protocol to generate dopaminergic (DA) neurons from iPSCs has been developed, and human ESCs were proven to function in the brains of rat and monkey PD models. We have developed a method of isolating DA neuron progenitors as a donor cell population, which allows safe and efficient transplantation. PMID:27599427

  2. Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy.

    Science.gov (United States)

    Pytel, Peter; Husain, Aliya; Moskowitz, Ivan; Raman, Jai; MacLeod, Heather; Anderson, Allen S; Burke, Martin; McNally, Elizabeth M

    2010-01-01

    A 41-year-old male with cardiomyopathy from an inherited beta myosin heavy-chain mutation underwent treatment for heart failure with intramyocardial cell transplantation. He received direct injections into his heart of autologous precursor cells isolated from his blood. He immediately suffered ventricular fibrillation. Although he was resuscitated, he experienced a prolonged downward course that prohibited his undergoing transplantation. His autopsy revealed marked fibrosis throughout the myocardium with areas of mononuclear cell infiltrate. This case highlights the potential adverse effects associated with intramyocardial therapy in the cardiomyopathic heart.

  3. Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy

    Science.gov (United States)

    Pytel, Peter; Husain, Aliya; Moskowitz, Ivan; Raman, Jai; MacLeod, Heather; Anderson, Allen S.; Burke, Martin; McNally, Elizabeth M.

    2010-01-01

    A 41 year old male with cardiomyopathy from an inherited β myosin heavy chain mutation underwent treatment for heart failure with intramyocardial cell transplantation. He received direct injections into his heart of autologous precursor cells isolated from his blood. He immediately suffered ventricular fibrillation. Although he was resuscitated, he experienced a prolonged downward course that prohibited his undergoing transplantation. His autopsy revealed marked fibrosis throughout the myocardium with areas of mononuclear cell infiltrate. This case highlights the potential adverse effects associated with intramyocardial therapy in the cardiomyopathic heart. PMID:19026577

  4. Microbiota modulation of myeloid cells in cancer therapy

    Science.gov (United States)

    Goldszmid, Romina S.; Dzutsev, Amiran; Viaud, Sophie; Zitvogel, Laurence; Restifo, Nicholas P.; Trinchieri, Giorgio

    2015-01-01

    Myeloid cells represent a major component of the tumor microenvironment where they play divergent dual roles: they can induce antitumor immune responses but mostly they promote immune evasion, tumor progression and metastases formation. Thus, strategies aiming at reprogramming the tumor microenvironment represent a promising immunotherapy approach. Myeloid cells respond to environmental factors including signals derived from commensal microbes. In this Cancer Immunology at the Crossroads overview we discuss recent advances on the effects of the commensal microbiota on myeloid-cell function and how that impacts the response to cancer therapy. PMID:25660553

  5. Stem cell therapy for cardiovascular disease : answering basic questions regarding cell behavior

    NARCIS (Netherlands)

    Bogt, Koen Elzert Adriaan van der

    2010-01-01

    Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the re

  6. Engineering a clinically-useful matrix for cell therapy.

    Science.gov (United States)

    Prestwich, Glenn D

    2008-01-01

    The design criteria for matrices for encapsulation of cells for cell therapy include chemical, biological, engineering, marketing, regulatory, and financial constraints. What is required is a biocompatible material for culture of cells in three-dimensions (3-D) that offers ease of use, experimental flexibility to alter composition and compliance, and a composition that would permit a seamless transition from in vitro to in vivo use. The challenge is to replicate the complexity of the native extracellular matrix (ECM) environment with the minimum number of components necessary to allow cells to rebuild a given tissue. Our approach is to deconstruct the ECM to a few modular components that can be reassembled into biomimetic materials that meet these criteria. These semi-synthetic ECMs (sECMs) employ thiol-modified derivatives of hyaluronic acid (HA) that can form covalently crosslinked, biodegradable hydrogels. These sECMs are "living" biopolymers, meaning that they can be crosslinked in the presence of cells or tissues to enable cell therapy and tissue engineering. Moreover, the sECMs allow inclusion of the appropriate biological cues needed to simulate the complexity of the ECM of a given tissue. Taken together, the sECM technology offers a manufacturable, highly reproducible, flexible, FDA-approvable, and affordable vehicle for cell expansion and differentiation in 3-D. PMID:19279714

  7. Risk factors in the development of stem cell therapy

    Directory of Open Access Journals (Sweden)

    Hermsen Harm PH

    2011-03-01

    Full Text Available Abstract Stem cell therapy holds the promise to treat degenerative diseases, cancer and repair of damaged tissues for which there are currently no or limited therapeutic options. The potential of stem cell therapies has long been recognised and the creation of induced pluripotent stem cells (iPSC has boosted the stem cell field leading to increasing development and scientific knowledge. Despite the clinical potential of stem cell based medicinal products there are also potential and unanticipated risks. These risks deserve a thorough discussion within the perspective of current scientific knowledge and experience. Evaluation of potential risks should be a prerequisite step before clinical use of stem cell based medicinal products. The risk profile of stem cell based medicinal products depends on many risk factors, which include the type of stem cells, their differentiation status and proliferation capacity, the route of administration, the intended location, in vitro culture and/or other manipulation steps, irreversibility of treatment, need/possibility for concurrent tissue regeneration in case of irreversible tissue loss, and long-term survival of engrafted cells. Together these factors determine the risk profile associated with a stem cell based medicinal product. The identified risks (i.e. risks identified in clinical experience or potential/theoretical risks (i.e. risks observed in animal studies include tumour formation, unwanted immune responses and the transmission of adventitious agents. Currently, there is no clinical experience with pluripotent stem cells (i.e. embryonal stem cells and iPSC. Based on their characteristics of unlimited self-renewal and high proliferation rate the risks associated with a product containing these cells (e.g. risk on tumour formation are considered high, if not perceived to be unacceptable. In contrast, the vast majority of small-sized clinical trials conducted with mesenchymal stem/stromal cells (MSC in

  8. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    Science.gov (United States)

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID:26155762

  9. Treating hearing disorders with cell and gene therapy

    Science.gov (United States)

    Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

    2014-12-01

    Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

  10. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    Directory of Open Access Journals (Sweden)

    A Patel

    2009-02-01

    Full Text Available Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the effects of inflammatory reactions on stem cells and extrapolate on information pertaining to cancer biology. The discussion focuses on integrins and cytokines, and identifies the transcription factor, nuclear factor-kappa B (NFκB as central to the inflammatory response. Since stem cell therapy has been proposed for type II diabetes mellitus, metabolic syndrome, pulmonary edema, these disorders are used as examples to discuss the roles of inflammatory mediators. We propose prospects for future research on targeting the NFκB signaling pathway. Finally, we explore the bridge between inflammation and stem cells, including neural stem cells and adult stem cells from the bone marrow. The implications of mesenchymal stem cells in regenerative medicine as pertaining to inflammation are vast based on their anti-inflammatory and immunosuppressive effects. Such features of stem cells offer great potential for therapy in graft-versus-host disease, conditions with a significant inflammatory component, and tissue regeneration.Keywords: mesenchymal stem cells, cancer, cytokines

  11. Perinatal stem-cell and gene therapy for hemoglobinopathies.

    Science.gov (United States)

    Surbek, Daniel; Schoeberlein, Andreina; Wagner, Anna

    2008-08-01

    Most genetic diseases of the lymphohematopoietic system, including hemoglobinopathies, can now be diagnosed early in gestation. However, as yet, prenatal treatment is not available. Postnatal therapy by hematopoietic stem cell (HSC) transplantation from bone marrow, mobilized peripheral blood, or umbilical cord blood is possible for several of these diseases, in particular for the hemoglobinopathies, but is often limited by a lack of histocompatible donors, severe treatment-associated morbidity, and preexisting organ damage that developed before birth. In-utero transplantation of allogeneic HSC has been performed successfully in various animal models and recently in humans. However, the clinical success of this novel treatment is limited to diseases in which the fetus is affected by severe immunodeficiency. The lack of donor cell engraftment in nonimmunocompromised hosts is thought to be due to immunologic barriers, as well as to competitive fetal marrow population by host HSCs. Among the possible strategies to circumvent allogeneic HLA barriers, the use of gene therapy by genetically corrected autologous HSCs in the fetus is one of the most promising approaches. The recent development of strategies to overcome failure of efficient transduction of quiescent hematopoietic cells using new vector constructs and transduction protocols opens new perspectives for gene therapy in general, as well as for prenatal gene transfer in particular. The fetus might be especially susceptible for successful gene therapy approaches because of the developing, expanding hematopoietic system during gestation and the immunologic naiveté early in gestation, precluding immune reaction towards the transgene by inducing tolerance. Ethical issues, in particular regarding treatment safety, must be addressed more closely before clinical trials with fetal gene therapy in human pregnancies can be initiated. PMID:18420474

  12. [Academic cell therapy facilities are challenged by European regulation on advanced therapy medicinal products].

    Science.gov (United States)

    Chabannon, Christian; Sabatier, Florence; Rial-Sebbag, Emmanuelle; Calmels, Boris; Veran, Julie; Magalon, Guy; Lemarie, Claude; Mahalatchimy, Aurélie

    2014-05-01

    Regulation (EC) n° 1394/2007 from the European Parliament and the Council describes a new category of health products termed « Advanced Therapy Medicinal Products » (ATMPs). ATMPs derive from cell engineering, tissue engineering or genetic manipulations, and can in some instances be combined with medical devices. ATMPs are distributed and administered to patients, after biotechnology or pharmaceutical companies have obtained a marketing authorization that is granted by the European Commission on the basis of the European Medicines Agency (EMA) assessment. Seven years after the publication of the regulation, few of these therapies have received a marketing authorization, and even fewer have met commercial success, suggesting that a number of medical and economic issues still need to be sorted out in order to achieve sustainability in this field. The coexistence of three sets of rules for three categories of health products that are biologically and medically related - ATMPs, ATMPs produced under the hospital exemption rule, and cell therapy products (CTPs) (a specific legal category in France) that have long been used in hematopoietic cell transplantation - constitutes a complex regulatory framework. This situation raises significant issues for historical as well as emerging operators in this moving field that are discussed thereafter.

  13. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    PhotoDynamic Therapy is a new concept for cancer treatment based on the interaction between light and a sensitizer, hematoporphyrin derivative (HPD) selectively retained by tumor cells which becomes toxic after light exposure. This effect decreases cell growth, through complex pathways. The aim of this study was to determine whether cellular polyamines, Put (Putrescine), Spd (Spermidine) and Spm (Spermine) were modified after PDT or not. These cations of small molecular weight are essential for cell growth and differentiation of normal and neoplastic cells. In this study intracellular contents of Put, Spd and Spm were determined on 2 sublines of rat colonic cancer cells cloned from the same rat cancer and forming progressive (PROb) and regressive (REGb) tumors. (author). 12 refs., 2 figs

  14. Neural stem cells and cell replacement therapy: making the right cells.

    Science.gov (United States)

    Bithell, Angela; Williams, Brenda P

    2005-01-01

    The past few years have seen major advances in the field of NSC (neural stem cell) research with increasing emphasis towards its application in cell-replacement therapy for neurological disorders. However, the clinical application of NSCs will remain largely unfeasible until a comprehensive understanding of the cellular and molecular mechanisms of NSC fate specification is achieved. With this understanding will come an increased possibility to exploit the potential of stem cells in order to manufacture transplantable NSCs able to provide a safe and effective therapy for previously untreatable neurological disorders. Since the pathology of each of these disorders is determined by the loss or damage of a specific neural cell population, it may be necessary to generate a range of NSCs able to replace specific neurons or glia rather than generating a generic NSC population. Currently, a diverse range of strategies is being investigated with this goal in mind. In this review, we focus on the relationship between NSC specification and differentiation and discuss how this information may be used to direct NSCs towards a particular fate.

  15. Gene Therapy In Squamous Cell Carcinoma – A Short Review

    Directory of Open Access Journals (Sweden)

    Soma Susan Varghese

    2011-07-01

    Full Text Available Oral cancer remains one of the leading causes of death world wide. Various means to destroy tumor cells preferentially have been developed; gene therapy is one among them with less treatment morbidity. Gene therapy involves the transfer of therapeutic or working copy of genes into a specific cell of an individual in order to repair a faulty copy of gene. The alteration can be accomplished by repairing or replacing the damaged DNA by various strategies and vectors. To date genetically altered viruses are commonly used as gene delivery vehicle (vector which has an advantage of evolutionary selection of host-virus relation. Non viral vectors which include the physical transfection of genes can be accomplished by electrophoration, microinjection, or use of ballistic particles and chemical transfection by forming liposomes.

  16. Stem cell therapy: a novel treatment option for cerebral malaria?

    Science.gov (United States)

    Wang, Wei; Qian, Hui; Cao, Jun

    2015-01-01

    Cerebral malaria, a severe form of the disease, is one of the most severe complications of infection with Plasmodium parasites and a leading cause of malaria mortality. Currently available antimalarial therapy has proven insufficient to prevent neurological complications and death in all cases of cerebral malaria. Souza and colleagues observed that transplantation of bone marrow-derived mesenchymal stromal cells (BM-MSCs) increased survival, reduced parasitemia, decreased malaria pigment accumulation in the spleen, liver and kidney, elevated Kupffer cell count in liver, alleviated renal injury and lung inflammation, and improved lung mechanics in an experimental mouse model of cerebral malaria. Although plenty of challenges lie ahead, their findings show the promise of BM-MSC therapy for the treatment of cerebral malaria. PMID:26253514

  17. Regenerative Medicine for the Kidney: Renotropic Factors, Renal Stem/Progenitor Cells, and Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Akito Maeshima

    2014-01-01

    Full Text Available The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  18. Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy

    OpenAIRE

    Lee B. Rivera; David Meyronet; Valérie Hervieu; Mitchell J. Frederick; Emily Bergsland; Gabriele Bergers

    2015-01-01

    Antiangiogenic therapy is commonly used in the clinic, but its beneficial effects are short-lived, leading to tumor relapse within months. Here, we found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in mouse models of pancreatic neuroendocrine and mammary tumors. In response, tumors reinitiated angiogenesis and immune suppression by activating PI3K signaling in all CD11b+ cells...

  19. Progress and challenges with clinical cell therapy in neurorestoratology

    OpenAIRE

    Huang H; Mao G; Chen L; Liu A

    2015-01-01

    Hongyun Huang,1–3 Gengsheng Mao,1 Lin Chen,4,5 Aibing Liu11General Hospital of Chinese People's Armed Police Forces,2Beijing Rehabilitation Hospital of Capital Medical University, 3Beijing Hongtianji Neuroscience Academy, 4Tsinghua University Yuquan Hospital, 5Medical Center, Tsinghua University, Beijing, People's Republic of ChinaAbstract: Cell therapies in the treatment of central nervous system disease and injury, such as spinal cord injury, multiple sclerosis, sequelae of st...

  20. Progress and challenges with clinical cell therapy in neurorestoratology

    OpenAIRE

    Huang, Hongyun

    2015-01-01

    Hongyun Huang,1–3 Gengsheng Mao,1 Lin Chen,4,5 Aibing Liu11General Hospital of Chinese People's Armed Police Forces,2Beijing Rehabilitation Hospital of Capital Medical University, 3Beijing Hongtianji Neuroscience Academy, 4Tsinghua University Yuquan Hospital, 5Medical Center, Tsinghua University, Beijing, People's Republic of ChinaAbstract: Cell therapies in the treatment of central nervous system disease and injury, such as spinal cord injury, multiple sclerosis, se...

  1. Optimising gene therapy of hypoparathyroidism with hematopoietic stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yi; L(U) Bing-jie; XU Ping; SONG Chun-fang

    2005-01-01

    Background The treatment of hypoparathyroidism (HPT) is still a difficult clinical problem, which necessitates a new therapy. Gene therapy of HPT has been valuable, but how to improve the gene transfer efficiency and expression stability is a problem. This study was designed to optimize the gene therapy of HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone (PTH) gene. Methods The human PTH gene was amplified by polymerase chain reaction (PCR) from pcDNA3.1-PTH vectors and inserted into murine stem cell virus (MSCV) vectors with double enzyme digestion (EcoRI and XhoI). The recombinant vectors were transfected into PA317 packaging cell lines by the lipofectin method and screened by G418 selective medium. The condensed recombinant retroviruses were extracted and used to infect HSCs, which were injected into mice suffering from HPT. The change of symptoms and serum levels of PTH and calcium in each group of mice were investigated. Results The human PTH gene was inserted into MSCV vectors successfully and the titres were up to 2×107 colony forming unit (CFU)/ml in condensed retroviral solution. The secretion of PTH reached 15 ng·10-6·cell-1 per 48 hours. The wild type viruses were not detected via PCR amplification, so they were safe for use. The mice suffering from HPT recovered quickly and the serum levels of calcium and PTH remained normal for about three months after the HSCs recombined with PTH were injected into them. The therapeutic effect of this method was better than simple recombinant retroviruses injection.Conclusions The recombinant retroviral vectors MSCV-PTH and the high-titre condensed retroviral solution recombined with the PTH gene are obtained. The recombinant retroviral solution could infect HSCs at a high rate of efficiency. The infected HSCs could cure HPT in mice. This method has provided theoretical evidence for the clinical gene therapy of HPT.

  2. Non-genetic engineering of cells for drug delivery and cell-based therapy.

    Science.gov (United States)

    Wang, Qun; Cheng, Hao; Peng, Haisheng; Zhou, Hao; Li, Peter Y; Langer, Robert

    2015-08-30

    Cell-based therapy is a promising modality to address many unmet medical needs. In addition to genetic engineering, material-based, biochemical, and physical science-based approaches have emerged as novel approaches to modify cells. Non-genetic engineering of cells has been applied in delivering therapeutics to tissues, homing of cells to the bone marrow or inflammatory tissues, cancer imaging, immunotherapy, and remotely controlling cellular functions. This new strategy has unique advantages in disease therapy and is complementary to existing gene-based cell engineering approaches. A better understanding of cellular systems and different engineering methods will allow us to better exploit engineered cells in biomedicine. Here, we review non-genetic cell engineering techniques and applications of engineered cells, discuss the pros and cons of different methods, and provide our perspectives on future research directions.

  3. Chimeric Antigen Receptor T Cell (Car T Cell Therapy In Hematology

    Directory of Open Access Journals (Sweden)

    Pinar Ataca

    2015-12-01

    Full Text Available It is well demonstrated that immune system can control and eliminate cancer cells. Immune-mediated elimination of tumor cells has been discovered and is the basis of both cancer vaccines and cellular therapies including hematopoietic stem cell transplantation (HSCT. Adoptive T cell transfer has been improved to be more specific and potent and cause less off-target toxicities. Currently, there are two forms of engineered T cells being tested in clinical trials: T cell receptor (TCR and chimeric antigen receptor (CAR modified T cells. On July 1, 2014, the United States Food and Drug Administration granted ‘breakthrough therapy’ designation to anti-CD19 CAR T cell therapy. Many studies were conducted to evaluate the beneficiaries of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical-clinical studies, effectiveness and drawbacks of this strategy.

  4. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  5. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  6. Targeting insulin-producing beta cells for regenerative therapy.

    Science.gov (United States)

    Migliorini, Adriana; Roscioni, Sara S; Lickert, Heiko

    2016-09-01

    Pancreatic beta cells differ in terms of glucose responsiveness, insulin secretion and proliferative capacity; however, the molecular pathways that regulate this cellular heterogeneity are unknown. We have identified the Wnt-planar cell polarity (PCP) effector Flattop (FLTP) as a biomarker that identifies mature beta cells in the islets of Langerhans. Interestingly, three-dimensional architecture and Wnt-PCP ligands are sufficient to trigger mouse and human beta cell maturation. These results highlight the fact that novel biomarkers shed light on the long-standing mystery of beta cell heterogeneity and identify the Wnt-PCP pathway as triggering beta cell maturation. Understanding heterogeneity in the islets of Langerhans might allow targeting of beta cell subpopulations for regenerative therapy and provide building principles for stem cell-derived islets. This review summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Harry Heimberg and colleagues, DOI: 10.1007/s00125-016-3879-6 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ). PMID:27412250

  7. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  8. Allogenic benefit in stem cell therapy: cardiac repair and regeneration.

    Science.gov (United States)

    Al-Daccak, R; Charron, D

    2015-09-01

    Stem cell (SC)-based therapies are a developing mean to repair, restore, maintain, or enhance organ functioning through life span. They are in particular a fast track to restore function in failing heart. Various types of SCs have been used in experimental and clinical studies showing the potential of these cells to revolutionize the treatment of heart diseases. Autologous cells have been privileged to overpass immunological barriers. The field has progressed tremendously and the hurdles, which have been largely overlooked in the excitement over the expected benefit the immunogenicity, have been revealed. Also, manufacturing of patient-specific clinical grade SC product, whether adult stem or reprogrammed induced pluripotent SCs, and the availability of these cells in sufficient amounts and status when needed is questionable. In contrast, adult SCs derived from healthy donors, thus allogeneic, have the advantage to be immediately available as an 'off-the-shelf' therapeutic product. The challenge is to overcome the immunological barriers to their transplantation. Recent research provided new insights into the mode of action and immune behavior of SCs in autologous as well as allogeneic settings. Lessons are learned and immune paradigms are changing: allogenicity, if balanced could be part of the dynamic and durable mechanisms that are critical to sustain cardiac regeneration and repair. We discuss the hurdles, lessons, and advances accomplished in the field through the progressive journey of cardiac-derived stem/progenitor cells toward allogeneic cardiac regenerative/reparative therapy. PMID:26206374

  9. Medulloblastoma stem cells: Promising targets in medulloblastoma therapy.

    Science.gov (United States)

    Huang, Guo-Hao; Xu, Qing-Fu; Cui, You-Hong; Li, Ningning; Bian, Xiu-Wu; Lv, Sheng-Qing

    2016-05-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long-term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. The CSCs are thought to be largely responsible for tumor initiation, maintenance, dissemination, and relapse; therefore, their pivotal roles have revealed them to be promising targets in MB therapy. Our growing understanding of the major medulloblastoma molecular subgroups and the derivation of some of these groups from specific stem or progenitor cells adds additional layers to the CSC knowledge base. Herein we review the current knowledge of MB stem cells, highlight the molecular mechanisms relating to MB relapse and leptomeningeal dissemination, and incorporate these with the need to develop more effective and accurate therapies for MB patients. PMID:27171351

  10. Human parthenogenetic embryonic stem cells: one potential resource for cell therapy

    Institute of Scientific and Technical Information of China (English)

    HAO Jie; HU WanWan; SHENG Chao; YU Yang; ZHOU Qi

    2009-01-01

    Pluripotent stem cells derived from somatic cells through such processes as nuclear transfer or in duced pluripotent stem (iPS) cells present an important model for biomedical research and provide potential resources for cell replacement therapies. However, the overall efficiency of the conversional nuclear transfer is very low and the safety issue remains a major concern for iPS cells. Embryonic stem cells (ESCs) generated from parthenogenetic embryos are one attractive alternative as a source of histocompatible cells and tissues for cell therapy. Recent studies on human parthenogenetic embryonic stem cells (hPG ESCs) have revealed that these ESCs are very similar to the hESCs derived from IVF or in vivo produced blastocysts in gene expression and other characteristics, but full differentiation and development potential of these hPG ESCs have to be further investigated before clinical research and therapeutic interventions. To generate various pluripotent stem cells, diverse reprogramming techniques and approaches will be developed and integrated. This may help elucidate the fundamental mechanisms underlying reprogramming and stem cell biology, and ultimately benefit cell therapy and regenerative medicine.

  11. Human parthenogenetic embryonic stem cells:one potential resource for cell therapy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Pluripotent stem cells derived from somatic cells through such processes as nuclear transfer or induced pluripotent stem(iPS) cells present an important model for biomedical research and provide potential resources for cell replacement therapies.However,the overall efficiency of the conversional nuclear transfer is very low and the safety issue remains a major concern for iPS cells.Embryonic stem cells(ESCs) generated from parthenogenetic embryos are one attractive alternative as a source of histocompatible cells and tissues for cell therapy.Recent studies on human parthenogenetic embryonic stem cells(hPG ESCs) have revealed that these ESCs are very similar to the hESCs derived from IVF or in vivo produced blastocysts in gene expression and other characteristics,but full differentiation and development potential of these hPG ESCs have to be further investigated before clinical research and therapeutic interventions.To generate various pluripotent stem cells,diverse reprogramming techniques and approaches will be developed and integrated.This may help elucidate the fundamental mechanisms underlying reprogramming and stem cell biology,and ultimately benefit cell therapy and regenerative medicine.

  12. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2015-04-01

    Full Text Available Multiple sclerosis (MS is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC and induced pluripotent stem cell (iPSCs derived precursor cells can modulate the autoimmune response in the central nervous system (CNS and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

  13. Cell therapy for ischaemic heart disease: focus on the role of resident cardiac stem cells

    NARCIS (Netherlands)

    S.A.J. Chamuleau; K.R. Vrijsen; D.G. Rokosh; X.L. Tang; J.J. Piek; R. Bolli

    2009-01-01

    Myocardial infarction results in loss of cardiomyocytes, scar formation, ventricular remodelling, and eventually heart failure. In recent years, cell therapy has emerged as a potential new strategy for patients with ischaemic heart disease. This includes embryonic and bone marrow derived stem cells.

  14. Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Philipp Koehler

    2012-01-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells.

  15. Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies.

    Science.gov (United States)

    Hoogduijn, M J; Roemeling-van Rhijn, M; Korevaar, S S; Engela, A U; Weimar, W; Baan, C C

    2011-12-01

    Mesenchymal stem cells (MSCs) have potential for therapeutic application as an immunomodulatory and regenerative agent. The immunogenicity and survival of MSCs after infusion are, however, not clear and evidence suggests that allogeneic but also autologous MSCs disappear rapidly after infusion. This may be associated with the susceptibility of MSCs to lysis by natural killer (NK) cells, possibly a result of culture-induced stress. In the present study we examined whether NK cell-mediated lysis of MSCs could be inhibited by immunosuppressive drugs. Human MSCs were isolated from adipose tissue and expanded in culture. Peripheral blood mononuclear cells were activated with interleukin (IL)-2 (200 U/ml) and IL-15 (10 ng/ml) for 7 days. CD3(-)CD16(+)CD56(+) NK cells were then isolated by fluorescence-activated cell sorting and added to europium-labeled MSCs for 4 hr in the presence or absence of immunosuppressive drugs. Lysis of MSCs was determined by spectrophotometric measurement of europium release. Nonactivated NK cells were not capable of lysing MSCs. Cytokine-activated NK cells showed upregulated levels of granzyme B and perforin and efficiently lysed allogeneic and autologous MSCs. Addition of tacrolimus, rapamycin or sotrastaurin to the lysis assay did not inhibit MSC killing. Furthermore, preincubation of activated NK cells with the immunosuppressive drugs for 24 hr before exposure to MSCs had no effect on MSC lysis. Last, addition of the immunosuppressants before and during the activation of NK cells, reduced NK cell numbers but did not affect their capacity to lyse MSCs. We conclude that the immunosuppressive drugs tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis of allogeneic and autologous MSCs by activated NK cells. Other approaches to controlling lysis of MSCs should be investigated, as controlling lysis may determine the efficacy of MSC therapy. PMID:21732766

  16. Autologous bone marrow cell therapy for peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Botti C

    2012-09-01

    Full Text Available C Botti, C Maione, A Coppola, V Sica, G CobellisDepartment of General Pathology, Second University of Naples, Naples, ItalyAbstract: Inadequate blood supply to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries – these injuries can range from mild (eg, leg ischemia to severe conditions (eg, myocardial infarction, stroke. Surgical and/or endovascular procedures provide cutting-edge treatment for patients with vascular disorders; however, a high percentage of patients are currently not treatable, owing to high operative risk or unfavorable vascular involvement. Therapeutic angiogenesis has recently emerged as a promising new therapy, promoting the formation of new blood vessels by the introduction of bone marrow–derived stem and progenitor cells. These cells participate in the development of new blood vessels, the enlargement of existing blood vessels, and sprouting new capillaries from existing blood vessels, providing evidence of the therapeutic utility of these cells in ischemic tissues. In this review, the authors describe peripheral arterial disease, an ischemic condition affecting the lower extremities, summarizing different aspects of vascular regeneration and discussing which and how stem cells restore the blood flow. The authors also present an overview of encouraging results from early-phase clinical trials using stem cells to treat peripheral arterial disease. The authors believe that additional research initiatives should be undertaken to better identify the nature of stem cells and that an intensive cooperation between laboratory and clinical investigators is needed to optimize the design of cell therapy trials and to maximize their scientific rigor. Only this will allow the results of these investigations to develop best clinical practices. Additionally, although a number of stem cell therapies exist, many treatments are performed outside international and national regulations and many

  17. Could cells from menstrual blood be a new source for cell-based therapies?

    Science.gov (United States)

    Zhang, Man-Jing; Liu, Bin; Xia, Wei; Sun, Zhi-Yong; Lu, Kai-Hua

    2009-03-01

    Human endometrium is a highly regenerative tissue and contains a low number of cells which have high replicative ability and differentiation efficiency. This has been identified by many scientists. When the fresh growth of tissue and blood vessels is shed during each menstrual cycle, some cells with regenerative capabilities are present. Reports have also indicated that these cells possess the capacity to trans-differentiate into mesodermal, ectodermal and endodermal lineages by using standard commercially available culture reagents and methodologies. Given the ease of extraction and pluripotency of this cell population, we propose it as a novel alternative to current cells sources for cell-based therapies. PMID:19101090

  18. Genetic engineering of stem cells for enhanced therapy.

    Science.gov (United States)

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  19. Autologous bone marrow stromal cells are promising candidates for cell therapy approaches to treat bone degeneration in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Angélique Lebouvier

    2015-11-01

    SCD-ON patients have a higher frequency of BMSCs that retain their bone regeneration potential. Our findings suggest that BMSCs isolated from SCD-ON patients can be used clinically in cell therapy approaches. This work provides important preclinical data that is necessary for the clinical application of expanded BMSCs in advanced therapies and medical products.

  20. Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

    Science.gov (United States)

    Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

    2004-10-01

    An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated. PMID:15585110

  1. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Science.gov (United States)

    2010-07-01

    ... Standards, 29 CFR part 1926; the Agriculture Standards, 29 CFR part 1928; the Shipyard Standards, 29 CFR part 1915; or the Longshoring Standards, 29 CFR part 1918. (3) All provisions of this section apply to... 29 Labor 5 2010-07-01 2010-07-01 false Servicing multi-piece and single piece rim wheels....

  2. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  3. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

    Institute of Scientific and Technical Information of China (English)

    Justin; D; Glenn; Katharine; A; Whartenby

    2014-01-01

    Mesenchymal stem cells(MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

  4. Last piece of the puzzle for ATLAS

    CERN Multimedia

    Clare Ryan

    At around 15.40 on Friday 29th February the ATLAS collaboration cracked open the champagne as the second of the small wheels was lowered into the cavern. Each of ATLAS' small wheels are 9.3 metres in diameter and weigh 100 tonnes including the massive shielding elements. They are the final parts of ATLAS' muon spectrometer. The first piece of ATLAS was installed in 2003 and since then many detector elements have journeyed down the 100 metre shaft into the ATLAS underground cavern. This last piece completes this gigantic puzzle.

  5. Cutting Mutually Congruent Pieces from Convex Regions

    CERN Document Server

    Nandakumar, R

    2010-01-01

    What is the shape of the 2D convex region P from which, when 2 mutually congruent convex pieces with maximum possible area are cut out, the highest fraction of the area of P is left over? When P is restricted to the set of all possible triangular shapes, our computational search yields an approximate upper bound of 5.6% on the minimum area wasted - when any triangle is given its best (most area utilizing) partition into 2 convex pieces. We then produce evidence for the general convex region which wastes the most area for its best convex 2-partition not being a triangle.

  6. Photothermal Therapy of Cancer Cells mediated by Blue Hydrogel Nanoparticles

    Science.gov (United States)

    Curry, Taeyjuana; Epstein, Tamir; Kopelman, Raoul

    2012-10-01

    Coomassie Blue dye has been covalently linked into a polyacrylamide nanoparticle matrix, so as to form nontoxic, biologically compatible, biodegradable and cell-specific targetable nanoparticles for photothermal therapy (PTT) of cancer. The nanoparticles were found to be approximately 80-95 nm in diameter, with an absorbance value of 0.52. Using an inexpensive, low intensity LED array light source (590nm, 25mW/cm^2), with 20 minute excitation times, at 37 , PTT induced hyperthermia/thermolysis in HeLa cells, in vitro, resulting in virtually complete cell death when observed 3 hours after exposure. These multifunctional particles have been previously used in cancer delineation, for surgery, and in photoacoustic imaging studies; the addition of the PTT function now enables a multi-pronged medical approach to cancer.

  7. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  8. 75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

    Science.gov (United States)

    2010-09-07

    ... HUMAN SERVICES Food and Drug Administration Cell and Gene Therapy Clinical Trials in Pediatric... public workshop entitled ``Cell and Gene Therapy Clinical Trials in Pediatric Populations.'' The purpose... therapy clinical trials in pediatric populations, as well as challenges and considerations in the...

  9. Photothermal therapy of cancer cells using novel hollow gold nanoflowers

    Directory of Open Access Journals (Sweden)

    Han J

    2014-01-01

    Full Text Available Jing Han,1 Jinru Li,1 Wenfeng Jia,1 Liangming Yao,2 Xiaoqin Li,1 Long Jiang,1 Yong Tian21Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, 2Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of ChinaAbstract: This article presents a new strategy for fabricating large gold nanoflowers (AuNFs that exhibit high biological safety under visible light and very strong photothermal cytotoxicity to HeLa cells under irradiation with near-infrared (NIR light. This particular type of AuNF was constructed using vesicles produced from a multiamine head surfactant as a template followed by depositing gold nanoparticles (AuNPs and growing their crystallites on the surface of vesicles. The localized surface plasmon-resonance spectrum of this type of AuNF can be easily modulated to the NIR region by controlling the size of the AuNFs. When the size of the AuNFs increased, biosafety under visible light improved and cytotoxicity increased under NIR irradiation. Experiments in vitro with HeLa cells and in vivo with small mice have been carried out, with promising results. The mechanism for this phenomenon is based on the hypothesis that it is difficult for larger AuNFs to enter the cell without NIR irradiation, but they enter the cell easily at the higher temperatures caused by NIR irradiation. We believe that these effects will exist in other types of noble metallic NPs and cancer cells. In addition, the affinity between AuNPs and functional biomolecules, such as aptamers and biomarkers, will make this type of AuNF a good recognition device in cancer diagnosis and therapy.Keywords: HeLa cells, endocytosis, cytotoxicity, AuNFs, NIR, cancer therapy

  10. Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy.

    Science.gov (United States)

    Baldwin, Kismet; Urbinati, Fabrizia; Romero, Zulema; Campo-Fernandez, Beatriz; Kaufman, Michael L; Cooper, Aaron R; Masiuk, Katelyn; Hollis, Roger P; Kohn, Donald B

    2015-05-01

    Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells, comprising ∼1%-3% of all CD34(+) cells, were isolated from healthy cord blood CD34(+) cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-β(AS3) -FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34(+) cells and required up to 40-fold less vector for transduction compared to bulk CD34(+) preparations containing an equivalent number of CD34(+) /CD38(-) cells. Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-) cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+) cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(-) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+) cells. This work provides initial evidence for the beneficial effects from isolating human CD34(+) /CD38(-) cells to use significantly less vector and potentially improve transduction for HSC gene therapy.

  11. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Ohi, S.

    Departments of Biochemistry &Molecular Biology, Genetics &Human Genetics, Pediatrics &Child Long-duration space missions require countermeasures against severe/invasive disorders in astronauts that are caused by space environments, such as hematological/cardiac abnormalities, bone/muscle losses, immunodeficiency, neurological disorders, and cancer. Some, if not all, of these disorders may be amenable to hematopoietic stem cell therapy and gene therapy. Growing evidence indicates that hematopoietic stem cells (HSCs) possess extraordinary plasticity to differentiate not only to all types of blood cells but also to various tissues, including bone, muscle, skin, liver and neuronal cells. Therefore, our working hypothesis is that the hematopoietic stem cell-based therapy, herein called as the hematopoietic stem cell therapy (HSCT), might provide countermeasure/prevention for hematological abnormalities, bone and muscle losses in space, thereby maintaining astronauts' homeostasis. Our expertise lies in recombinant adeno-associated virus (rAAV)-mediated gene therapy for the hemoglobinopathies, -thalassemia and sickle cell disease (Ohi S, Kim BC, J Pharm Sci 85: 274-281, 1996; Ohi S, et al. Grav Space Biol Bull 14: 43, 2000). As the requisite steps in this protocol, we established procedures for purification of HSCs from both mouse and human bone marrow in 1 G. Furthermore, we developed an easily harvestable, long-term liquid suspension culture system, which lasts more than one year, for growing/expanding HSCs without stromal cells. Human globin cDNAs/gene were efficiently expressed from the rAAVs in the mouse HSCs in culture. Additionally, the NASA Rotating Wall Vessel (RWV) culture system is being optimized for the HSC growth/expansion. Thus, using these technologies, the above hypothesis is being investigated by the ground-based experiments as follows: 1) -thalassemic mice (C57BL/6-Hbbth/Hbbth, Hbd-minor) are transplanted with normal isologous HSCs to correct the

  12. Selenite benefits embryonic stem cells therapy in Parkinson's disease.

    Science.gov (United States)

    Tian, L-P; Zhang, S; Xu, L; Li, W; Wang, Y; Chen, S-D; Ding, J-Q

    2012-09-01

    Embryonic stem cells (ESC) transplantation is a potential therapeutic approach for Parkinson's disease (PD). However, one of the main challenges to this therapy is the post-transplantation survival of dopaminergic (DA) neurons. In this study, mouse ESC were differentiated into DA neurons by a modified serum free protocol. These ESC-derived neurons were then transplanted into striatum of 6-OHDA lesioned rat. The viability of grafted DA neurons was decreased, accompanied by activated microglia and high levels of proinflammatory factors, such as TNF-α and iNOS, in the graft niche. This suggested that the local neuroinflammation might be involved in the reduced cells viability. Selenite, the source of essential micronutrient selenium, could inhibit NF-κB p65 nuclear translocation and subsequently reduce iNOS, COX-2 and TNF-α expression in LPS-treated BV2 cells in a dose dependant manner. Before the transplantation of ESC-derived DA neurons, 6-OHDA lesioned rats were intraperitoneally injected with selenite. The expression levels of TNF-α and iNOS were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment. To sum up, selenite might benefit ESCs transplantation therapy in PD through anti-inflammation effects.

  13. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Vanessa M. Doulames

    2016-04-01

    Full Text Available Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient’s own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI—even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury.

  14. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury.

    Science.gov (United States)

    Doulames, Vanessa M; Plant, Giles W

    2016-01-01

    Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient's own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI-even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury. PMID:27070598

  15. "Cell therapy for stroke: use of local astrocytes"

    Directory of Open Access Journals (Sweden)

    Melek eChouchane

    2012-10-01

    Full Text Available Stroke refers to a variety of conditions caused by the occlusion or hemorrhage of blood vessels supplying the brain, which is one of the main causes of death and the leading cause of disability worldwide. In the last years, cell-based therapies have been proposed as a new approach to ameliorate post stroke deficits. However, the most appropriate type of cell to be used in such therapies, as well as their sources, remains a matter of intense research. A good candidate cell should, in principle, display high plasticity to generate diverse types of neurons and, at the same type, low risk to cause undesired outcomes, such as malignant transformation. Recently, a new approach grounded on the reprogramming of endogenous astrocytes towards neuronal fates emerged as an alternative to restore neurological functions in several central nervous system diseases. In this perspective, we review data about the potential of astrocytes to become functional neurons following expression of neurogenic genes and discuss the potential benefits and risks of reprogramming astrocytes in the glial scar to replace neurons lost after stroke.

  16. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. PMID:26486823

  17. Sorafenib and sunitinib: novel targeted therapies for renal cell cancer.

    Science.gov (United States)

    Grandinetti, Cheryl A; Goldspiel, Barry R

    2007-08-01

    Renal cell cancer (RCC) is a relatively uncommon malignancy, with 51,190 cases expected to be diagnosed in 2007. Localized disease is curable by surgery; however, locally advanced or metastatic disease is not curable in most cases and, until recently, had a limited response to drug treatment. Historically, biologic response modifiers or immunomodulating agents were tested in clinical trials based on observations that some cases of RCC can spontaneously regress. High-dose aldesleukin is approved by the United States Food and Drug Administration as a treatment for advanced RCC; however, the drug is associated with a high frequency of severe adverse effects. Responses have been observed with low-dose aldesleukin and interferon alfa, but with little effect on overall survival. Sorafenib and sunitinib are novel therapies that target growth factor receptors known to be activated by the hypoxia-inducible factor and the Ras-Raf/MEK/ERK pathways. These pathways are important in the pathophysiology of RCC. Sorafenib and sunitinib have shown antitumor activity as first- and second-line therapy in patients with cytokine-refractory metastatic RCC who have clear-cell histology. Although complete responses are not common, both drugs promote disease stabilization and increase progression-free survival. This information suggests that disease stabilization may be an important determinant for response in RCC and possibly other cancers. Sorafenib and sunitinib are generally well tolerated and are considered first- and second-line treatment options for patients with advanced clear cell RCC. In addition, sorafenib and sunitinib have shown promising results in initial clinical trials evaluating antitumor activity in patients who are refractory to other antiangiogenic therapy. The most common toxicities with both sorafenib and sunitinib are hand-foot syndrome, rash, fatigue, hypertension, and diarrhea. Research is directed toward defining the optimal use of these new agents. PMID:17655513

  18. Cell death mechanisms vary with photodynamic therapy dose and photosensitizer

    Science.gov (United States)

    He, Jin; Oleinick, Nancy L.

    1995-03-01

    Mouse lymphoma L5178Y-R cells respond to photodynamic therapy (PDT) by undergoing rapid apoptosis, which is induced by PDT-activated signal transduction initiating in the damaged cellular membranes. To relate the level of PDT damage and photosensitizer to the mechanism of cell death, apoptosis has been detected by agarose gel electrophoresis of fragmented DNA and quantified by flow cytometry of cells after staining with Hoechst33342 and propidium iodide, a technique which can distinguish between live, apoptotic, and necrotic cells. When the silicon phthalocyanine Pc 4 or Pc 12 served as photosensitizer, lethal doses (as defined by clonogenic assay) of PDT induced apoptosis in essentially all cells, whereas supralethal doses prevented the characteristic degradation of DNA into oligonucleosomal fragments. In contrast with aluminum phthalocyanine (AlPc) cells died by apoptosis after all doses studied. It appears that high PDT doses with Pc 4 or Pc 12 damage enzymes needed to carry out the program of apoptosis; the absence of this effect with AlPc suggests either a different intracellular location or different photocytotoxic mechanism for the two photosensitizers.

  19. The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus.

    Science.gov (United States)

    Rushkevich, Yu N; Kosmacheva, S M; Zabrodets, G V; Ignatenko, S I; Goncharova, N V; Severin, I N; Likhachev, S A; Potapnev, M P

    2015-08-01

    We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients. The cell therapy was safe for the patients.

  20. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2003-01-01

    It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  1. Cell and gene therapy in Duchenne muscular dystrophy.

    Science.gov (United States)

    Morgan, J E

    1994-02-01

    Experiments in mice have supported the idea of treating Duchenne muscular dystrophy (DMD) by implanting normal muscle precursor cells into dystrophin-deficient muscles. However, similar experiments on DMD patients have had little success. Gene therapy for DMD, by introducing dystrophin constructs via retroviral or adenoviral vectors, has been shown to be possible in the mouse, but the efficiency and safety aspects of this technique will have to be carefully examined before similar experiments can be attempted in man. Direct injection of dystrophin cDNA constructs into mdx muscles has given rise to very low levels of dystrophin and this may be a possibility for the treatment of heart muscle. PMID:7514447

  2. Can one classify finite Postnikov pieces?

    CERN Document Server

    Moller, Jesper M

    2009-01-01

    We compare the classical approach of constructing finite Postnikov systems by k-invariants and the global approach of Dwyer, Kan, and Smith. We concentrate on the case of 3-stage Postnikov pieces and provide examples where a classification is feasible. In general though the computational difficulty of the global approach is equivalent to that of the classical one.

  3. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Roach, Allana Nicole; Brezo, Jelena

    2002-01-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

  4. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    Science.gov (United States)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  5. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    NARCIS (Netherlands)

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.

    2014-01-01

    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for re

  6. Maintaining clarity: Review of maintenance therapy in non-small cell lung cancer

    OpenAIRE

    Dearing, Kristen R; Sangal, Ashish; Weiss, Glen J

    2014-01-01

    The purpose of this article is to review the role of maintenance therapy in the treatment of advanced non-small cell lung cancer (NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are ad...

  7. Pluripotent stem cells as a potential tool for disease modelling and cell therapy in diabetes.

    Science.gov (United States)

    Abdelalim, Essam M; Bonnefond, Amélie; Bennaceur-Griscelli, Annelise; Froguel, Philippe

    2014-06-01

    Diabetes mellitus is the most prevailing disease with progressive incidence worldwide. To date, the pathogenesis of diabetes is far to be understood, and there is no permanent treatment available for diabetes. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs). ESCs and iPSCs have a great potential to differentiate into all cell types, and they have a high ability to differentiate into insulin-secreting β cells. Obtaining PSCs genetically identical to the patient presenting with diabetes has been a longstanding dream for the in vitro modeling of disease and ultimately cell therapy. For several years, somatic cell nuclear transfer (SCNT) was the method of choice to generate patient-specific ESC lines. However, this technology faces ethical and practical concerns. Interestingly, the recently established iPSC technology overcomes the major problems of other stem cell types including the lack of ethical concern and no risk of immune rejection. Several iPSC lines have been recently generated from patients with different types of diabetes, and most of these cell lines are able to differentiate into insulin-secreting β cells. In this review, we summarize recent advances in the differentiation of pancreatic β cells from PSCs, and describe the challenges for their clinical use in diabetes cell therapy. Furthermore, we discuss the potential use of patient-specific PSCs as an in vitro model, providing new insights into the pathophysiology of diabetes.

  8. Freezing of Fresh Wharton's Jelly From Human Umbilical Cords Yields High Post-Thaw Mesenchymal Stem Cell Numbers for Cell-Based Therapies.

    Science.gov (United States)

    Fong, Chui-Yee; Subramanian, Arjunan; Biswas, Arijit; Bongso, Ariff

    2016-04-01

    Some cord blood banks freeze entire pieces of UC (mixed cord, MC) which after post-thaw yields mixed heterogeneous populations of mesenchymal stem cells (MSCs) from all its microanatomical compartments. Freezing of such entire tissues results in sub-optimal post-thaw cell recovery because of poor cryoprotectant diffusion and intracellular ice-formation, heat and water transport issues, and damage to intercellular junctions. To develop a simple method of harvesting pure homogeneous MSCs for cord blood banks, we compared the post-thaw behavior of three groups of frozen UC tissues: (i) freshly harvested WJ without cell separation; (ii) MSCs isolated from WJ (WJSC); and (iii) MC, WJ, and WJSC produced high post-thaw cell survival rates (93.52 ± 6.12% to 90.83 ± 4.51%) and epithelioid monolayers within 24 h in primary culture whereas post-thaw MC explants showed slow growth with mixed epithelioid and fibroblastic cell outgrowths after several days. Viability and proliferation rates of post-thawed WJ and hWJSC were significantly greater than MC. Post-thaw WJ and WJSC produced significantly greater CD24(+) and CD108(+) fluorescence intensities and significantly lower CD40(+) contaminants. Post-thaw WJ and WJSC produced significantly lesser annexin-V-positive and sub-G1 cells and greater degrees of osteogenic and chondrogenic differentiation compared to MC. qRT-PCR analysis of post-thaw MC showed significant decreases in anti-apoptotic gene expression (SURVIVIN, BCL2) and increases in pro-apoptotic (BAX) and cell cycle regulator genes (P53, P21, ROCK 1) compared to WJ and WJSC. We conclude that freezing of fresh WJ is a simple and reliable method of generating large numbers of clinically utilizable MSCs for cell-based therapies. PMID:26365815

  9. Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy?

    Science.gov (United States)

    Sanina, Cristina; Hare, Joshua M

    2015-07-17

    Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine.

  10. Extended rhodamine photosensitizers for photodynamic therapy of cancer cells.

    Science.gov (United States)

    Davies, Kellie S; Linder, Michelle K; Kryman, Mark W; Detty, Michael R

    2016-09-01

    Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). PMID:27246858

  11. Translating stem cell therapies: the role of companion animals in regenerative medicine

    OpenAIRE

    Volk, Susan W.; Theoret, Christine

    2013-01-01

    Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell r...

  12. Cell Therapy in Patients with Critical Limb Ischemia

    Directory of Open Access Journals (Sweden)

    Rita Compagna

    2015-01-01

    Full Text Available Critical limb ischemia (CLI represents the most advanced stage of peripheral arterial obstructive disease (PAOD with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life.

  13. Dendritic Cells and Multiple Sclerosis: Disease, Tolerance and Therapy

    Directory of Open Access Journals (Sweden)

    Mohammad G. Mohammad

    2012-12-01

    Full Text Available Multiple sclerosis (MS is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact. The majority of therapies for this disease were developed in, or are beneficial in experimental autoimmune encephalomyelitis (EAE, the animal model of MS. While known to target adaptive anti-CNS immune responses, they also target, the innate immune arm. This mini-review focuses on the role of dendritic cells (DCs, the professional antigen presenting cells of the innate immune system. The evidence for a role for DCs in the appropriate regulation of anti-CNS autoimmune responses and their role in MS disease susceptibility and possible therapeutic utility are discussed. Additionally, the current controversy regarding the evidence for the presence of functional DCs in the normal CNS is reviewed. Furthermore, the role of CNS DCs and potential routes of their intercourse between the CNS and cervical lymph nodes are considered. Finally, the future role that this nexus between the CNS and the cervical lymph nodes might play in site directed molecular and cellular therapy for MS is outlined.

  14. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    Science.gov (United States)

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  15. The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy

    Science.gov (United States)

    Foldvari, Marianna; Chen, Ding Wen

    2016-01-01

    Regeneration of damaged retinal ganglion cells (RGC) and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufficient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also discuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efficient and representative in vitro models for rapid and reliable screening in the drug development process.

  16. The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma:a case for gene therapy

    Institute of Scientific and Technical Information of China (English)

    Marianna Foldvari; Ding Wen Chen

    2016-01-01

    Regeneration of damaged retinal ganglion cells (RGC) and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufifcient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also dis-cuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efifcient and representativein vitro models for rapid and reliable screening in the drug development process.

  17. Invited review: Stem cells and muscle diseases: advances in cell therapy strategies.

    Science.gov (United States)

    Negroni, Elisa; Gidaro, Teresa; Bigot, Anne; Butler-Browne, Gillian S; Mouly, Vincent; Trollet, Capucine

    2015-04-01

    Despite considerable progress to increase our understanding of muscle genetics, pathophysiology, molecular and cellular partners involved in muscular dystrophies and muscle ageing, there is still a crucial need for effective treatments to counteract muscle degeneration and muscle wasting in such conditions. This review focuses on cell-based therapy for muscle diseases. We give an overview of the different parameters that have to be taken into account in such a therapeutic strategy, including the influence of muscle ageing, cell proliferation and migration capacities, as well as the translation of preclinical results in rodent into human clinical approaches. We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so far [CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), muscle-derived stem cells (MuStem), embryonic stem cells (ES) and induced pluripotent stem cells (iPS)]. Finally, we provide an update of ongoing clinical trials using cell therapy strategies.

  18. Cell therapy for ischaemic heart disease: focus on the role of resident cardiac stem cells.

    Science.gov (United States)

    Chamuleau, S A J; Vrijsen, K R; Rokosh, D G; Tang, X L; Piek, J J; Bolli, R

    2009-05-01

    Myocardial infarction results in loss of cardiomyocytes, scar formation, ventricular remodelling, and eventually heart failure. In recent years, cell therapy has emerged as a potential new strategy for patients with ischaemic heart disease. This includes embryonic and bone marrow derived stem cells. Recent clinical studies showed ostensibly conflicting results of intracoronary infusion of autologous bone marrow derived stem cells in patients with acute or chronic myocardial infarction. Anyway, these results have stimulated additional clinical and pre-clinical studies to further enhance the beneficial effects of stem cell therapy. Recently, the existence of cardiac stem cells that reside in the heart itself was demonstrated. Their discovery has sparked intense hope for myocardial regeneration with cells that are obtained from the heart itself and are thereby inherently programmed to reconstitute cardiac tissue. These cells can be detected by several surface markers (e.g. c-kit, Sca-1, MDR1, Isl-1). Both in vitro and in vivo differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells has been demonstrated, and animal studies showed promising results on improvement of left ventricular function. This review will discuss current views regarding the feasibility of cardiac repair, and focus on the potential role of the resident cardiac stem and progenitor cells. (Neth Heart J 2009;17:199-207.).

  19. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.;

    2008-01-01

    used for MSC cultivation in animal studies simulating clinical stem cell therapy. MATERIAL AND METHODS: Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP-accepted medium (EMEA medium) or in one of four other media. RESULTS: FACS...... compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease Udgivelsesdato: 2008......OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...

  20. Quality compliance in the shift from cell transplantation to cell therapy in non-pharma environments.

    Science.gov (United States)

    Vives, Joaquim; Oliver-Vila, Irene; Pla, Arnau

    2015-08-01

    Along with academic and charitable organizations, transfusion centers have ventured into the stem cell field, with the aim of testing of novel cell-based therapeutics in a clinical setting for future marketing approval. The fact that quality management structures, which are required for compliance with good scientific practice regulations, were originally designed for product development in corporate environments represents a major challenge for many developers. In this Commentary, challenges that non-pharmaceutical institutions must overcome to translate cell-based products into clinical therapies will be discussed from a quality standpoint. Furthermore, our development experience for a mesenchymal stromal cell-based therapy will be shared as a case study. PMID:25769789

  1. The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine

    International Nuclear Information System (INIS)

    Light therapy commonly referred to as low level laser therapy can alter cellular functions and clinical conditions. Some of the commonly reported in vitro and in vivo effects of light therapy include cellular proliferation, alterations in the inflammatory response to injury, and increases in mitochondrial respiration and adenosine triphosphate synthesis. Based on the known effects of light on cells and tissues in general and on reports in the last 5 years on the interaction of light with stem cells, evidence is mounting indicating that light therapy could greatly benefit stem cell regenerative medicine. Experiments on a variety of harvested adult stem cells demonstrate that light therapy enhances differentiation and proliferation of the cells and alters the expression of growth factors in a number of different types of adult stem cells and progenitors in vitro. It also has the potential to attenuate cytotoxic effects of drugs used to purge harvested autologous stem cells and to increase survival of transplanted cells.

  2. The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine

    Science.gov (United States)

    Anders, Juanita; Moges, Helina; Wu, Xingjia; Ilev, Ilko; Waynant, Ronald; Longo, Leonardo

    2010-05-01

    Light therapy commonly referred to as low level laser therapy can alter cellular functions and clinical conditions. Some of the commonly reported in vitro and in vivo effects of light therapy include cellular proliferation, alterations in the inflammatory response to injury, and increases in mitochondrial respiration and adenosine triphosphate synthesis. Based on the known effects of light on cells and tissues in general and on reports in the last 5 years on the interaction of light with stem cells, evidence is mounting indicating that light therapy could greatly benefit stem cell regenerative medicine. Experiments on a variety of harvested adult stem cells demonstrate that light therapy enhances differentiation and proliferation of the cells and alters the expression of growth factors in a number of different types of adult stem cells and progenitors in vitro. It also has the potential to attenuate cytotoxic effects of drugs used to purge harvested autologous stem cells and to increase survival of transplanted cells.

  3. TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients

    DEFF Research Database (Denmark)

    Kvistborg, Pia; Shu, Chengyi Jenny; Heemskerk, Bianca;

    2012-01-01

    There is strong evidence that both adoptive T cell transfer and T cell checkpoint blockade can lead to regression of human melanoma. However, little data are available on the effect of these cancer therapies on the tumor-reactive T cell compartment. To address this issue we have profiled therapy-...

  4. Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

    International Nuclear Information System (INIS)

    Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

  5. WT1-specific T cell receptor gene therapy: improving TCR function in transduced T cells.

    Science.gov (United States)

    Stauss, Hans J; Thomas, Sharyn; Cesco-Gaspere, Michela; Hart, Daniel P; Xue, Shao-An; Holler, Angelika; King, Judy; Wright, Graham; Perro, Mario; Pospori, Constantina; Morris, Emma

    2008-01-01

    Adoptive transfer of antigen-specific T lymphocytes is an attractive form of immunotherapy for haematological malignancies and cancer. The difficulty of isolating antigen-specific T lymphocytes for individual patients limits the more widespread use of adoptive T cell therapy. The demonstration that cloned T cell receptor (TCR) genes can be used to produce T lymphocyte populations of desired specificity offers new opportunities for antigen-specific T cell therapy. The first trial in humans demonstrated that TCR gene-modified T cells persisted for an extended time period and reduced tumor burden in some patients. The WT1 protein is an attractive target for immunotherapy of leukemia and solid cancer since elevated expression has been demonstrated in AML, CML, MDS and in breast, colon and ovarian cancer. In the past, we have isolated high avidity CTL specific for a WT1-derived peptide presented by HLA-A2 and cloned the TCR alpha and beta genes of a WT1-specific CTL line. The genes were inserted into retroviral vectors for transduction of human peripheral blood T lymphocytes of leukemia patients and normal donors. The treatment of leukemia-bearing NOD/SCID mice with T cells transduced with the WT1-specific TCR eliminated leukemia cells in the bone marrow of most mice, while treatment with T cells transduced with a TCR of irrelevant specificity did not diminish the leukemia burden. In order to improve the safety and efficacy of TCR gene therapy, we have developed lentiviral TCR gene transfer. In addition, we employed strategies to enhance TCR expression while avoiding TCR mis-pairing. It may be possible to generate dominant TCR constructs that can suppress the expression of the endogenous TCR on the surface of transduced T cells. The development of new TCR gene constructs holds great promise for the safe and effective delivery of TCR gene therapy for the treatment of malignancies. PMID:17855129

  6. Stem cell-based therapies for acute radiation syndrome

    International Nuclear Information System (INIS)

    Exposure to high doses of ionizing radiation in the event of accidental or intentional incident such as nuclear/radiological terrorism can lead to debilitating injuries to multiple organs resulting in death within days depending on the amount of radiation dose and the quality of radiation. Unfortunately, there is not a single FDA-licensed drug approved against acute radiation injury. The RadStem Center for Medical Countermeasures against Radiation (RadStem CMGR) program at Einstein is developing stem cell-based therapies to treat acute radiation syndrome (ARS). We have demonstrated that intravenous transplantation of bone marrow-derived and adipose-derived stromal cells, consisting of a mixture of mesenchymal, endothelial and myeloid progenitors can mitigate mice exposed to whole body irradiation of 12 Gy or whole abdominal irradiation of up to 20 Gy. We identified a variety of growth and differentiation factors that individually is unable to improve survival of animals exposed to lethal irradiation, but when administered sequentially mitigates radiation injury and improves survival. We termed this phenomenon as synthetic survival and describe a new paradigm whereby the 'synthetic survival' of irradiated tissues can be promoted by systemic administration of growth factors to amplify residual stem cell clonogens post-radiation exposure, followed by a differentiation factor that favors tissue stem cell differentiation. Synthetic survival can be applied to mitigate lethal radiation injury in multiple organs following radiation-induced hematopoeitic, gastrointestinal and pulmonary syndromes. (author)

  7. T Cell Epitope Peptide Therapy for Allergic Diseases.

    Science.gov (United States)

    O'Hehir, Robyn E; Prickett, Sara R; Rolland, Jennifer M

    2016-02-01

    Careful selection of dominant T cell epitope peptides of major allergens that display degeneracy for binding to a wide array of MHC class II molecules allows induction of clinical and immunological tolerance to allergen in a refined treatment strategy. From the original concept of peptide-induced T cell anergy arising from in vitro studies, proof-of-concept murine models and flourishing human trials followed. Current randomized, double-blind, placebo-controlled clinical trials of mixtures of T cell-reactive short allergen peptides or long contiguous overlapping peptides are encouraging with intradermal administration into non-inflamed skin a preferred delivery. Definitive immunological mechanisms are yet to be resolved but specific anergy, Th2 cell deletion, immune deviation, and Treg induction seem implicated. Significant efficacy, particularly with short treatment courses, in a range of aeroallergen therapies (cat, house dust mite, grass pollen) with inconsequential non-systemic adverse events likely heralds a new class of therapeutic for allergy, Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE). PMID:26768622

  8. Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the changes of the cell cycle regulators ATM,Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by cisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM,Chk2 and p53 of HeLa cells with and without cisplatin were detected by RT-PCR and Western blot,respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin...

  9. Clinical significance of metallothioneins in cell therapy and nanomedicine

    Directory of Open Access Journals (Sweden)

    Sharma S

    2013-04-01

    Full Text Available Sushil Sharma,1 Afsha Rais,1 Ranbir Sandhu,1 Wynand Nel,1 Manuchair Ebadi21Saint James School of Medicine, Bonaire, The Netherlands; 2Department of Pharmacology, Physiology, and Therapeutics, Center of Excellence in Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USAAbstract: Mammalian metallothioneins (MTs are low molecular weight (6–7 kDa cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs. MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide–ubiquinone oxidoreductase (complex-1, a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs

  10. Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

    Science.gov (United States)

    Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

    2015-01-01

    Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

  11. Would cancer stem cells affect the future investment in stem cell therapy.

    Science.gov (United States)

    Rameshwar, Pranela

    2012-04-20

    The common goal within the overwhelming interests in stem cell research is to safely translate the science to patients. Although there are various methods by which this goal can be reached, this editorial emphasizes the safety of mesenchymal stem cell (MSC) transplant and possible confounds by the growing information on cancer stem cells (CSCs). There are several ongoing clinical trials with MSCs and their interactions with CSCs need to be examined. The rapid knowledge on MSCs and CSCs has now collided with regards to the safe treatment of MSCs. The information discussed on MSCs can be extrapolated to other stem cells with similar phenotype and functions such as placenta stem cells. MSCs are attractive for cell therapy, mainly due to reduced ethical concerns, ease in expansion and reduced ability to be transformed. Also, MSCs can exert both immune suppressor and tissue regeneration simultaneously. It is expected that any clinical trial with MSCs will take precaution to ensure that the cells are not transformed. However, going forward, the different centers should be aware that MSCs might undergo oncogenic events, especially as undifferentiated cells or early differentiated cells. Another major concern for MSC therapy is their ability to promote tumor growth and perhaps, to protect CSCs by altered immune responses. These issues are discussed in light of a large number of undiagnosed cancers.

  12. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy

    Science.gov (United States)

    Sarang, Shabari; Viswanathan, Chandra

    2016-01-01

    Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes. PMID:27426087

  13. Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease.

    Science.gov (United States)

    Levy, Yossef S; Stroomza, Merav; Melamed, Eldad; Offen, Daniel

    2004-01-01

    The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular, is that they will improve patient's functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft's excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their

  14. ET-67SUICIDE GENE THERAPY FOR GLIOMA USING MULTILINEAGE-DEFFERENTIATING STRESS ENDURING (MUSE) CELLS

    OpenAIRE

    Yamasaki, Tomohiro; Wakao, Shohei; KAWAJI, Hiroshi; Suzuki, Tomo; Kamio, Yoshinobu; AMANO, SHINJI; Sameshima, Tetsuro; Sakai, Naoto; TOKUYAMA, TSUTOMU; Dezawa, Mari; NAMBA, HIROKI

    2014-01-01

    INTRODUCTION: We have been investigating cell-based glioma gene therapy using various kinds of stem cells transduced with the herpes simplex virus thymidine kinase gene (HSVtk). In our previous study, we used SSEA3/CD105 double-positive multilineage-differentiating stress-enduring (Muse) cells transduced with HSVtk (Muse-tk cells) as the vehicle for HSVtk/ganciclovir (GCV) gene therapy. We demonstrated a potent in vitro tumoricidal bystander effect for various glioma cells. In the present stu...

  15. New advances in the mesenchymal stem cells therapy against skin flaps necrosis.

    Science.gov (United States)

    Zhang, Fu-Gui; Tang, Xiu-Fa

    2014-09-26

    Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

  16. New advances in the mesenchymal stem cells therapy against skin flaps necrosis

    Institute of Scientific and Technical Information of China (English)

    Fu-Gui; Zhang; Xiu-Fa; Tang

    2014-01-01

    Mesenchymal stem cells(MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

  17. Skin-Directed Therapies in Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Nguyen, Cuong V; Bohjanen, Kimberly A

    2015-10-01

    Early stage mycosis fungoides represents the most common clinical presentation of cutaneous lymphoma, with skin-directed therapies long established in its treatment. These therapies continue to change as new treatment regimens emerge. Other skin-directed treatments include light and radiation therapy. Therapies with higher levels of evidence and less systemic toxicity are usually preferred as first-line treatment. However, even these established therapies, like topical corticosteroids and carmustine, lack randomized clinical trials to establish their efficacy. Research is also needed to further define the role of combination topical therapies and how skin-directed therapies can be used as adjuvants to systemic medications. PMID:26433841

  18. Cell Death Pathways in Photodynamic Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Michael R. Hamblin

    2011-06-01

    Full Text Available Photodynamic therapy (PDT is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2 are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.

  19. Cell Death Pathways in Photodynamic Therapy of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mroz, Pawel, E-mail: pmroz@partners.org [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Yaroslavsky, Anastasia [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Boston University College of Engineering, Boston, MA 02114 (United States); Kharkwal, Gitika B [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Hamblin, Michael R. [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139 (United States)

    2011-06-03

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.

  20. Cell Death Pathways in Photodynamic Therapy of Cancer

    International Nuclear Information System (INIS)

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT

  1. Selective thermal neutron capture therapy of cancer cells using their specific functional differentiation

    International Nuclear Information System (INIS)

    The theory and the history of selective thermal neutron capture therapy for malignant melanoma, thermal neutron capture therapy which has been developed by authors, synthesis and effects of 10B-compounds accumulating in melanoma cells and absorbing thermal neutron easily, and many experiments concerning this therapy were reviewed and discussed. (Tsunoda, M.)

  2. Clinical relevance of stem cell therapies in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Amit K Srivastava

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, characterized by the progressive loss of both upper and lower motor neurons, is a fatal neurodegenerative disorder. This disease is often accompanied by a tremendous physical and emotional burden not only for the patients, but also for their families and friends as well. There is no clinically relevant treatment available for ALS. To date, only one Food and Drug Administration (FDA-approved drug, Riluzole, licensed 18 years ago, has been proven to marginally prolong patients′ survival without improving the quality of their lives. Because of the lack of an effective drug treatment and the promising outcomes from several preclinical studies, researchers have highlighted this disease as a suitable candidate for stem cell therapy. This review article highlights the finding of key preclinical studies that present a rationale for the use of different types of stem cells for the treatment of ALS, and the most recent updates on the stem cell-based ALS clinical trials around the world.

  3. Re: Engineered Nanoparticles Induce Cell Apoptosis: Potential for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-09-01

    Full Text Available Engineered nanoparticles (ENPs have been widely applied in industry, biology and medicine recently (i.e. clothes, sunscreens, cosmetics, foods, diagnostic medicine, imaging and drug delivery. There are many kinds of manufactured nanomaterial products including TiO2, ZnO, CeO2, Fe2O3, and CuO (as metal oxide nanoparticles as well as gold, silver, platinum and palladium (as metal nanoparticles, and other carbon-based ENP’s such as carbon nanotububes and quantum dots. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs and cause toxic effects. In many researches, ENP effects on the cancer cells of different organs with related cell apoptosis were noted (AgNP, nano-Cr2O3, Au-Fe2O3 NPs, nano-TiO2, nano-HAP, nano-Se, MoO3 nanoplate, Realgar nanoparticles. ENPs, with their unique properties, such as surface charge, particle size, composition and surface modification with tissue recognition ligands or antibodies, has been increasingly explored as a tool to carry small molecular weight drugs as well as macromolecules for cancer therapy, thus generating the new concept “nanocarrier”. Direct induction of cell apoptosis by ENPs provides an opportunity for cancer treatment. In the century of nanomedicine that depends on development of the nanotechnology, ENPs have a great potential for application in cancer treatment with minimal side effects.

  4. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

    Science.gov (United States)

    Chen, L W; Kuang, F; Wei, L C; Ding, Y X; Yung, K K L; Chan, Y S

    2011-06-01

    Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for

  5. Salvage therapy in patients with germ cell tumors.

    Science.gov (United States)

    Einhorn, Lawrence H

    2015-01-01

    Testicular cancer is the most curable metastatic solid tumor. Initial chemotherapy is evidence based with risk stratification into three prognostic categories: good, intermediate, and advanced disease. Guidelines for disease management following progression after initial cisplatin combination chemotherapy are less clear. Options include salvage surgery for patients with anatomically confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose chemotherapy with carboplatin plus etoposide with peripheral blood stem cell transplantation. Proper interpretation of a presumed relapse can be complicated. Growing masses on imaging studies might reflect a growing teratoma. Persistent elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP) are only an indication for salvage therapy if there is a definitive rise in the tumor marker. Elevated and rising serum hCG as the only evidence of recurrence can be because of cross reactivity with luteinizing hormone or usage of marijuana rather than progressive cancer. Elevated liver function tests can cause rising serum AFP. PMID:25993183

  6. Cell transplantation and gene therapy in muscular dystrophy.

    Science.gov (United States)

    Morgan, J E; Partridge, T A

    1992-09-01

    Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin-negative fibres to -positive, with consequent improvement in muscle histology. Direct injection of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin-positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man. PMID:1365921

  7. Stem cell models of polyglutamine diseases and their use in cell-based therapies

    Directory of Open Access Journals (Sweden)

    Evangelia eSiska

    2015-07-01

    Full Text Available Polyglutamine diseases are fatal neurological disorders that affect the central nervous system. They are caused by mutations in disease genes that contain CAG trinucleotide expansions in their coding regions. These mutations are translated into expanded glutamine chains in pathological proteins. Mutant proteins induce cytotoxicity, form intranuclear aggregates and cause neuronal cell death in specific brain regions. At the moment there is no cure for these diseases and only symptomatic treatments are available. Here, we discuss novel therapeutic approaches that aim in neuronal cell replacement using induced pluripotent or adult stem cells. Additionally, we present the beneficial effect of genetically engineered mesenchymal stem cells and their use as disease models or RNAi/gene delivery vehicles. In combination with their paracrine and cell-trophic properties, such cells may prove useful for the development of novel therapies against polyglutamine diseases.

  8. Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy

    OpenAIRE

    Julia Terhune; Erik Berk; Czerniecki, Brian J.

    2013-01-01

    The success of cellular immunotherapies against cancer requires the generation of activated CD4+ and CD8+ T-cells. The type of T-cell response generated (e.g., Th1 or Th2) will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17) play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for ...

  9. Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

    Directory of Open Access Journals (Sweden)

    Goichi Yanai

    Full Text Available Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types, promote angiogenesis and modulate inflammation, thereby studied as an enhancer of islet function and engraftment. Electrofusion is an efficient method of cell fusion and nuclear reprogramming occurs in hybrid cells between different cell types. Therefore, we hypothesized that electrofusion between MSC and islet cells may yield robust islet cells for diabetes therapy. We establish a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. Renal subcapsular transplantation of fusion cells prepared from suboptimal islet mass (1,000 islets that did not correct hyperglycemia even if co-transplanted with MSCs, caused slow but consistent lowering of blood glucose with significant weight gain within the observation period in streptozotocin-induced diabetic rats. In the fusion cells between rat islet cells and mouse MSCs, RT-PCR showed new expression of both rat MSC-related genes and mouse β-cell-related genes, indicating bidirectional reprogramming of both β-cell and MSCs nuclei. Moreover, decreased caspase3 expression and new expression of Ki-67 in the islet cell nuclei suggested alleviated apoptosis and gain of proliferative capability, respectively. These results show that electrofusion between MSCs and islet cells yield special cells with β-cell function and robustness of MSCs and seems feasible for novel therapeutic strategy for diabetes

  10. A Review of Gene Delivery and Stem Cell Based Therapies for Regenerating Inner Ear Hair Cells

    Directory of Open Access Journals (Sweden)

    Michael S. Detamore

    2011-09-01

    Full Text Available Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  11. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    International Nuclear Information System (INIS)

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved. (letter)

  12. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Science.gov (United States)

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  13. Cellular plasticity : the good, the bad, and the ugly? Microenvironmental influences on progenitor cell therapy

    NARCIS (Netherlands)

    Moonen, Jan-Renier A. J.; Harmsen, Martin C.; Krenning, Guido

    2012-01-01

    Progenitor cell based therapies have emerged for the treatment of ischemic cardiovascular diseases where there is insufficient endogenous repair. However, clinical success has been limited, which challenges the original premise that transplanted progenitor cells would orchestrate repair. In this rev

  14. Plasticity of Cancer Cell Invasion-Mechanisms and Implications for Therapy.

    Science.gov (United States)

    Te Boekhorst, V; Friedl, P

    2016-01-01

    Cancer cell migration is a plastic and adaptive process integrating cytoskeletal dynamics, cell-extracellular matrix and cell-cell adhesion, as well as tissue remodeling. In response to molecular and physical microenvironmental cues during metastatic dissemination, cancer cells exploit a versatile repertoire of invasion and dissemination strategies, including collective and single-cell migration programs. This diversity generates molecular and physical heterogeneity of migration mechanisms and metastatic routes, and provides a basis for adaptation in response to microenvironmental and therapeutic challenge. We here summarize how cytoskeletal dynamics, protease systems, cell-matrix and cell-cell adhesion pathways control cancer cell invasion programs, and how reciprocal interaction of tumor cells with the microenvironment contributes to plasticity of invasion and dissemination strategies. We discuss the potential and future implications of predicted "antimigration" therapies that target cytoskeletal dynamics, adhesion, and protease systems to interfere with metastatic dissemination, and the options for integrating antimigration therapy into the spectrum of targeted molecular therapies. PMID:27613134

  15. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    Institute of Scientific and Technical Information of China (English)

    Quan Jiang

    2016-01-01

    Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance im-aging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

  16. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    Directory of Open Access Journals (Sweden)

    Quan Jiang

    2016-01-01

    Full Text Available Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

  17. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Ramsahai, Shweta; Kim, Bak C.; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2004-02-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from β-galactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  18. Progress and challenges in the development of a cell-based therapy for hemophilia A.

    Science.gov (United States)

    Fomin, M E; Togarrati, P P; Muench, M O

    2014-12-01

    Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells.

  19. Defining the potential for cell therapy for vascular disease using animal models

    OpenAIRE

    Gulati, Rajiv; Simari, Robert D.

    2009-01-01

    Cell-based therapeutics are currently being developed for a wide array of unmet medical needs. As obstructive vascular disease is the major cause of mortality in the world, cell-based strategies aimed at developing novel therapies or improving current therapies are currently under study. These studies are based on the evolving understanding of the biology of vascular progenitor cells, which has in turn led to the availability of well-defined sources of vascular cells for delivery. Crucial to ...

  20. Implication of Cord Blood for Cell-Based Therapy in Refractory Childhood Diseases

    OpenAIRE

    Lee, Young-Ho

    2010-01-01

    Since cord blood (CB) contains hematopoietic stem cells as well as a mixture of multipotent stem cells, CB has the ability to give rise to hematopoietic, epithelial, endothelial and neural tissues. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. This review focuses clinical and pre-clinical application of CB cell-based therapy for inherited metabolic diseases as well as tissu...

  1. Cell Therapy Strategies vs. Paracrine Effect in Huntington’s Disease

    OpenAIRE

    Wooseok Im; Manho Kim

    2014-01-01

    Huntington’s disease (HD) is a genetic neurodegenerative disorder. The most common symptom of HD is abnormal involuntary writhing movements, called chorea. Antipsychotics and tetrabenazine are used to alleviate the signs and symptoms of HD. Stem cells have been investigated for use in neurodegenerative disorders to develop cell therapy strategies. Recent evidence indicates that the beneficial effects of stem cell therapies are actually mediated by secretory molecules, as well as cell replacem...

  2. Cell based therapies for ischemic stroke: From basic science to bedside

    OpenAIRE

    Liu, Xinfeng; Ye, Ruidong; Yan, Tao; Yu, Shan Ping; Wei, Ling; Xu, Gelin; Fan, Xinying; Jiang, Yongjun; Stetler, R. Anne; Liu, George; Chen, Jieli

    2013-01-01

    Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenito...

  3. Indocyanine green-mediated photodynamic therapy on glioblastoma cells in vitro

    OpenAIRE

    AK, Ayşe; Kaya, Özgür; Turgut Coşan, Didem; Gülsoy, Murat

    2015-01-01

    Photodynamic therapy (PDT) is an alternative therapy which is administered with non-toxic drugs, called photosensitizers (PSs), along with irradiation at a specific wavelength of light to damage tumor cells. Different wavelengths of light sources and photosensitizers have been investigated in treatment of many cancer types. In this study, we investigated whether photodynamic therapy using indocyanine green (ICG), also a cyanine dye used in medical diagnostics, can be used to inhibit cell prol...

  4. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    Science.gov (United States)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  5. The prospect of precision therapy for renal cell carcinoma.

    Science.gov (United States)

    Ciccarese, Chiara; Brunelli, Matteo; Montironi, Rodolfo; Fiorentino, Michelangelo; Iacovelli, Roberto; Heng, Daniel; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade. From being a malignancy orphan of effective therapies, kidney cancer has become today a tumor with several treatment options. Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). In this complex scenario it is important to find prognostic and predictive factors that can help in decision making in the treatment of mRCC.

  6. Targeted therapy for renal cell carcinoma: The next lap

    Directory of Open Access Journals (Sweden)

    Ravindran Kanesvaran

    2014-01-01

    Full Text Available Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR, there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.

  7. The multivariate Piecing-Together approach revisited

    OpenAIRE

    Aulbach, Stefan; Falk, Michael; Hofmann, Martin

    2011-01-01

    The univariate Piecing-Together approach (PT) fits a univariate generalized Pareto distribution (GPD) to the upper tail of a given distribution function in a continuous manner. A multivariate extension was established by Aulbach et al. (2012a): The upper tail of a given copula C is cut off and replaced by a multivariate GPD-copula in a continuous manner, yielding a new copula called a PT-copula. Then each margin of this PT-copula is transformed by a given univariate distribution function. Thi...

  8. Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Ander Abarrategi

    2016-01-01

    Full Text Available Osteosarcoma (OS is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.

  9. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  10. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  11. Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Corinne A Lee-Kubli; Paul Lu

    2015-01-01

    The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell ther-apies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.

  12. Photodynamic therapy-induced programmed cell death in carcinoma cell lines

    Science.gov (United States)

    He, Xiao-Yan; Sikes, Robert A.; Thomsen, Sharon L.; Chung, L.; Jacques, Steven L.

    1993-06-01

    The mode of cell death following photodynamic therapy (PDT) was investigated from the perspective of programmed cell death (apoptosis). Human prostate carcinoma cells (PC3), human non-small cell lung carcinoma (H322a), and rat mammary carcinoma (MTF7) were treated by PDT following sensitization with dihematoporphyrin ether (DHE). The response of these carcinoma cell lines to PDT was variable. An examination of extracted cellular DNA by gel electrophoresis showed the characteristic DNA ladder pattern indicative of internucleosomal cleavage of DNA during apoptosis. MTF7 and PC3 responded to PDT by inducing apoptosis while H322a had no apoptotic response. The magnitude of the response and the PDT dosage required to induce the effect were different in PC3 and MTF7. MTF7 cells responded with rapid apoptosis at the dose of light and drug that yielded 50% cell death (LD50). In contrast, PC3 showed only marginal apoptosis at the LD50 but had a marked response at the LD85. Furthermore, the onset of apoptosis followed slower kinetics in PC3 (2 hr - 4 hr) than in MTF7 (cells were killed by PDT but failed to exhibit any apoptotic response. This study indicates that apoptosis may occur during PDT induced cell death, but this pathway is not universal for all cancer cell lines.

  13. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.

    Science.gov (United States)

    Li, Rui; Rezk, Ayman; Miyazaki, Yusei; Hilgenberg, Ellen; Touil, Hanane; Shen, Ping; Moore, Craig S; Michel, Laure; Althekair, Faisal; Rajasekharan, Sathy; Gommerman, Jennifer L; Prat, Alexandre; Fillatreau, Simon; Bar-Or, Amit

    2015-10-21

    B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF-expressing B cells efficiently activated myeloid cells in a GM-CSF-dependent manner, and in vivo, BCDT resulted in a GM-CSF-dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)- and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10-expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases. PMID:26491076

  14. Use of an apparatus for separating magnetic pieces of material

    NARCIS (Netherlands)

    Rem, P.C.; Berkhout, S.P.M.

    2010-01-01

    Using of an apparatus for separating magnetic pieces of scrap-material of a first group from magnetic pieces of scrap- material of a second group, wherein a mixture of pieces of scrap-material from the first group and from the second group is collectively transported with a conveyor to a separating

  15. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients.

    Science.gov (United States)

    Busca, Alessandro; Pagano, Livio

    2016-01-01

    Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan. Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. When introduced in 1959, Amphotericin B deoxycholate (d-AmB) was a life-saving drug, and the clinical experience over 50 years has proven that this compound is effective although toxic. Given the superior safety profile, lipid formulations of AmB have now replaced d-AmB in many circumstances. Similarly, echinocandins have been investigated as initial therapy for IA in several clinical trials including HSCT recipients, although the results were moderately disappointing leading to a lower grade of recommendation in the majority of published guidelines. Azoles represent the backbone of therapy for treating immunocompromised patients with IFI, including voriconazole and the newcomer isavuconazole; in addition, large studies support the use of mold-active azoles, namely voriconazole and posaconazole, as antifungal prophylaxis in HSCT recipients. The aim of the present review is to summarize the clinical application of antifungal agents most commonly employed in the treatment of IFI. PMID:27648202

  16. Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?

    Directory of Open Access Journals (Sweden)

    Jo N Fleming

    Full Text Available BACKGROUND: Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue, antiangiogenic interferon alpha (overexpressed in the scleroderma dermis and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon alpha and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE: These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease

  17. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    OpenAIRE

    Kasten, P; I Beyen; Egermann, M.; AJ Suda; AA Moghaddam; Zimmermann, G; R Luginbühl

    2008-01-01

    In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC) before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM), clusters of differentiation (CD), proliferation and differentiation capacities of the MSC. A volume reduction protoc...

  18. Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation in mouse and man

    Science.gov (United States)

    Holland, Amanda M.; Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Ghosh, Arnab

    2016-01-01

    Hematopoietic stem cell transplantation is a curative therapy for hematological malignancies. T cell deficiency following transplantation is a major cause of morbidity and mortality. In this review, we discuss adoptive transfer of committed precursor cells to enhance T cell reconstitution and improve overall prognosis after transplantation. PMID:19015856

  19. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    OpenAIRE

    Sabine Wislet-Gendebien; Emerence Laudet; Virginie Neirinckx; Bernard Rogister

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In th...

  20. Host-based Th2 cell therapy for prolongation of cardiac allograft viability.

    Directory of Open Access Journals (Sweden)

    Shoba Amarnath

    Full Text Available Donor T cell transfusion, which is a long-standing approach to prevent allograft rejection, operates indirectly by alteration of host T cell immunity. We therefore hypothesized that adoptive transfer of immune regulatory host Th2 cells would represent a novel intervention to enhance cardiac allograft survival. Using a well-described rat cardiac transplant model, we first developed a method for ex vivo manufacture of rat host-type Th2 cells in rapamycin, with subsequent injection of such Th2.R cells prior to class I and class II disparate cardiac allografting. Second, we determined whether Th2.R cell transfer polarized host immunity towards a Th2 phenotype. And third, we evaluated whether Th2.R cell therapy prolonged allograft viability when used alone or in combination with a short-course of cyclosporine (CSA therapy. We found that host-type Th2.R cell therapy prior to cardiac allografting: (1 reduced the frequency of activated T cells in secondary lymphoid organs; (2 shifted post-transplant cytokines towards a Th2 phenotype; and (3 prolonged allograft viability when used in combination with short-course CSA therapy. These results provide further support for the rationale to use "direct" host T cell therapy for prolongation of allograft viability as an alternative to "indirect" therapy mediated by donor T cell infusion.

  1. Note onset deviations as musical piece signatures.

    Directory of Open Access Journals (Sweden)

    Joan Serrà

    Full Text Available A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields.

  2. Note onset deviations as musical piece signatures.

    Science.gov (United States)

    Serrà, Joan; Özaslan, Tan Hakan; Arcos, Josep Lluis

    2013-01-01

    A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields. PMID:23935971

  3. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies?

    DEFF Research Database (Denmark)

    Lepperdinger, Günter; Brunauer, Regina; Jamnig, Angelika;

    2008-01-01

    restricts their proliferation and differentiation efficiency. It however also limits the yield of sufficient numbers of cells needed for therapy. Another issue is to eliminate contamination of expanding cells with serum-bound pathogenic agents in order to reduce the risks for infection. A recent technical...... advancement, which applies human serum platelet lysates as an alternative source for growth factors and essential supplements, allows the unimpaired proliferation of MSC in the absence of animal sera. Here, we present an update regarding cellular senescence of MSC and recent insights concerning potential...

  4. Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

    Science.gov (United States)

    Wang, Xin; Liu, Kai; Yang, Guangbao; Cheng, Liang; He, Lu; Liu, Yumeng; Li, Yonggang; Guo, Liang; Liu, Zhuang

    2014-07-01

    Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via

  5. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy.

    Science.gov (United States)

    de Rham, Casimir; Villard, Jean

    2014-01-01

    Great hopes have been placed on human pluripotent stem (hPS) cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS) cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues. PMID:25126584

  6. Stem cells for cell replacement therapy: a therapeutic strategy for HD?

    Science.gov (United States)

    Rosser, Anne; Svendsen, Clive N

    2014-09-15

    Much interest has been expressed over the last couple of decades in the potential application of stem cells to medicine, both for research and diagnostic tools and as a source of donor cells for therapeutic purposes. Potential therapeutic applications include replacement of cells in many body organs where the capacity for intrinsic repair is limited, including the pancreas, heart, and brain. A key challenge is to generate the relevant donor cell types, and this is particularly challenging in the brain where the number of different neuronal subtypes is so great. Although dopamine neuron replacement in Parkinson's disease has been the focus of most clinical studies, great interest has been shown in this approach for other disorders, including Huntington's disease. Replacing complete neural circuits in the adult brain is clearly challenging, and there are many other complexities with regard to both donor cells and host. This article presents the pros and cons of taking a cell therapy approach in Huntington's disease. It considers the implantation both of cells that are already of the same neural subtype as those lost in the disease process (ie, primary fetal cells derived from the developing striatum) and those derived from stem cells, which require "directing" toward that phenotype. PMID:25216372

  7. Potential and Limitation of HLA-Based Banking of Human Pluripotent Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Casimir de Rham

    2014-01-01

    Full Text Available Great hopes have been placed on human pluripotent stem (hPS cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA, the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues.

  8. Stem cells for cell replacement therapy: a therapeutic strategy for HD?

    Science.gov (United States)

    Rosser, Anne; Svendsen, Clive N

    2014-09-15

    Much interest has been expressed over the last couple of decades in the potential application of stem cells to medicine, both for research and diagnostic tools and as a source of donor cells for therapeutic purposes. Potential therapeutic applications include replacement of cells in many body organs where the capacity for intrinsic repair is limited, including the pancreas, heart, and brain. A key challenge is to generate the relevant donor cell types, and this is particularly challenging in the brain where the number of different neuronal subtypes is so great. Although dopamine neuron replacement in Parkinson's disease has been the focus of most clinical studies, great interest has been shown in this approach for other disorders, including Huntington's disease. Replacing complete neural circuits in the adult brain is clearly challenging, and there are many other complexities with regard to both donor cells and host. This article presents the pros and cons of taking a cell therapy approach in Huntington's disease. It considers the implantation both of cells that are already of the same neural subtype as those lost in the disease process (ie, primary fetal cells derived from the developing striatum) and those derived from stem cells, which require "directing" toward that phenotype.

  9. Glioblastoma Therapy with Cytotoxic Mesenchymal Stromal Cells Optimized by Bioluminescence Imaging of Tumor and Therapeutic Cell Response

    OpenAIRE

    Maria Alieva; Bagó, Juli R.; Elisabet Aguilar; Carolina Soler-Botija; Vila, Olaia F.; Joan Molet; Gambhir, Sanjiv S.; Nuria Rubio; Jerónimo Blanco

    2012-01-01

    Genetically modified adipose tissue derived mesenchymal stromal cells (hAMSCs) with tumor homing capacity have been proposed for localized therapy of chemo- and radiotherapy resistant glioblastomas. We demonstrate an effective procedure to optimize glioblastoma therapy based on the use of genetically modified hAMSCs and in vivo non invasive monitoring of tumor and therapeutic cells. Glioblastoma U87 cells expressing Photinus pyralis luciferase (Pluc) were implanted in combination with hAMSCs ...

  10. Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy

    Science.gov (United States)

    Turinetto, Valentina; Vitale, Emanuela; Giachino, Claudia

    2016-01-01

    Regenerative medicine is extensively interested in developing cell therapies using mesenchymal stem cells (MSCs), with applications to several aging-associated diseases. For successful therapies, a substantial number of cells are needed, requiring extensive ex vivo cell expansion. However, MSC proliferation is limited and it is quite likely that long-term culture evokes continuous changes in MSCs. Therefore, a substantial proportion of cells may undergo senescence. In the present review, we will first present the phenotypic characterization of senescent human MSCs (hMSCs) and their possible consequent functional alterations. The accumulation of oxidative stress and dysregulation of key differentiation regulatory factors determine decreased differentiation potential of senescent hMSCs. Senescent hMSCs also show a marked impairment in their migratory and homing ability. Finally, many factors present in the secretome of senescent hMSCs are able to exacerbate the inflammatory response at a systemic level, decreasing the immune modulation activity of hMSCs and promoting either proliferation or migration of cancer cells. Considering the deleterious effects that these changes could evoke, it would appear of primary importance to monitor the occurrence of senescent phenotype in clinically expanded hMSCs and to evaluate possible ways to prevent in vitro MSC senescence. An updated critical presentation of the possible strategies for in vitro senescence monitoring and prevention constitutes the second part of this review. Understanding the mechanisms that drive toward hMSC growth arrest and evaluating how to counteract these for preserving a functional stem cell pool is of fundamental importance for the development of efficient cell-based therapeutic approaches. PMID:27447618

  11. Colorectal cancer stem cells : regulation of the phenotype and implications for therapy resistance

    OpenAIRE

    Emmink, B.L.

    2014-01-01

    In this thesis different aspects of cancer stem cells in colorectal cancer are discribed. We focus on the therapy resistance of cancer stem cells and the effect that reactive oxygen species and hypoxia have on the cancer stem cell phenotype. For this purpose a novel culture method to propagate cancer stem cells form resected tumor specimens was used.

  12. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

    Science.gov (United States)

    Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

    2016-09-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition.

  13. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

    Science.gov (United States)

    Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

    2016-09-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition. PMID:27424148

  14. Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

    Institute of Scientific and Technical Information of China (English)

    DONG Fang; HA Xiao-qin

    2010-01-01

    Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was "endothelial progenitor cells".Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

  15. Fractal dimension analysis of complexity in Ligeti piano pieces

    Science.gov (United States)

    Bader, Rolf

    2005-04-01

    Fractal correlation dimensional analysis has been performed with whole solo piano pieces by Gyrgy Ligeti at every 50ms interval of the pieces. The resulting curves of development of complexity represented by the fractal dimension showed up a very reasonable correlation with the perceptional density of events during these pieces. The seventh piece of Ligeti's ``Musica ricercata'' was used as a test case. Here, each new part of the piece was followed by an increase of the fractal dimension because of the increase of information at the part changes. The second piece ``Galamb borong,'' number seven of the piano Etudes was used, because Ligeti wrote these Etudes after studying fractal geometry. Although the piece is not fractal in the strict mathematical sense, the overall structure of the psychoacoustic event-density as well as the detailed event development is represented by the fractal dimension plot.

  16. Relaxation Algorithm of Piecing-Error for Sub-Images

    Institute of Scientific and Technical Information of China (English)

    LI Yueping; TANG Pushan

    2001-01-01

    During the process of automatic image recognition or automatic reverse design of IC, people often encounter the problem that some sub-images must be pieced together into a whole image. In the traditional piecing algorithm for sub images, a large accumulated error will be made. In this paper, a relaxation algorithm of piecing-error for sub-images is presented. It can eliminate the accumulated error in the traditional algorithm and greatly improve the quality of pieced image. Based on an initial pieced image, one can continuously adjust the center of every sub-image and its angle to lessen the error between the adjacent sub-images, so the quality of pieced image can be improved. The presented results indicate that the proposed algorithm can dramatically decrease the error while the quality of ultimate pieced image is still acceptable. The time complexity of this algorithm is O(n In n).

  17. Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy.

    Science.gov (United States)

    Terhune, Julia; Berk, Erik; Czerniecki, Brian J

    2013-01-01

    The success of cellular immunotherapies against cancer requires the generation of activated CD4⁺ and CD8⁺ T-cells. The type of T-cell response generated (e.g., Th1 or Th2) will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17) play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for IL-17, other studies have shown an anti-tumor function. The induction of polarized T-cell responses can be regulated by dendritic cells (DCs). DCs are key regulators of the immune system with the ability to affect both innate and adaptive immune responses. These properties have led many researchers to study the use of ex vivo manipulated DCs for the treatment of various diseases, such as cancer and autoimmune diseases. While Th1/Tc1 cells are traditionally used for their potent anti-tumor responses, mounting evidence suggests Th17/Tc17 cells should be utilized by themselves or for the induction of optimal Th1 responses. It is therefore important to understand the factors involved in the induction of both type-1 and type-17 T-cell responses by DCs. PMID:26344346

  18. Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Julia Terhune

    2013-11-01

    Full Text Available The success of cellular immunotherapies against cancer requires the generation of activated CD4+ and CD8+ T-cells. The type of T-cell response generated (e.g., Th1 or Th2 will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17 play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for IL-17, other studies have shown an anti-tumor function. The induction of polarized T-cell responses can be regulated by dendritic cells (DCs. DCs are key regulators of the immune system with the ability to affect both innate and adaptive immune responses. These properties have led many researchers to study the use of ex vivo manipulated DCs for the treatment of various diseases, such as cancer and autoimmune diseases. While Th1/Tc1 cells are traditionally used for their potent anti-tumor responses, mounting evidence suggests Th17/Tc17 cells should be utilized by themselves or for the induction of optimal Th1 responses. It is therefore important to understand the factors involved in the induction of both type-1 and type-17 T-cell responses by DCs.

  19. Mesenchymal Stem Cells for Regenerative Therapy: Optimization of Cell Preparation Protocols

    Directory of Open Access Journals (Sweden)

    Chiho Ikebe

    2014-01-01

    Full Text Available Administration of bone marrow-derived mesenchymal stem cells (MSCs is an innovative approach for the treatment of a range of diseases that are not curable by current therapies including heart failure. A number of clinical trials have been completed and many others are ongoing; more than 2,000 patients worldwide have been administered with culture-expanded allogeneic or autologous MSCs for the treatment of various diseases, showing feasibility and safety (and some efficacy of this approach. However, protocols for isolation and expansion of donor MSCs vary widely between these trials, which could affect the efficacy of the therapy. It is therefore important to develop international standards of MSC production, which should be evidence-based, regulatory authority-compliant, of good medical practice grade, cost-effective, and clinically practical, so that this innovative approach becomes an established widely adopted treatment. This review article summarizes protocols to isolate and expand bone marrow-derived MSCs in 47 recent clinical trials of MSC-based therapy, which were published after 2007 onwards and provided sufficient methodological information. Identified issues and possible solutions associated with the MSC production methods, including materials and protocols for isolation and expansion, are discussed with reference to relevant experimental evidence with aim of future clinical success of MSC-based therapy.

  20. Results of radiation therapy for squamous cell carcinoma of vulva

    Energy Technology Data Exchange (ETDEWEB)

    Tsukiyama, Iwao; Kakehi, Masae; Ono, Ryosuke (National Cancer Center, Tokyo (Japan). Hospital)

    1984-04-01

    From 1962 to 1982, 20 cases of patients with squamous cell carcinoma of the vulva were treated by radiation alone at National Cancer Center Hospital, Tokyo. 80% (16/20) of these cases were over 60 years old. Treatment was made by interstitial irradiation (Radium needle or Au-Grain) and external irradiation (Betatron electron or Linac X-rays), alone or with various combinations. As for the stage of these cases, Stage I was 3 cases (15%), Stage II was 5 (25%) and Stage III was 12 (60%). Serious complications after treatment were observed in 15% (3/20) and all cases were treated with external irradiation alone. The 5 year survival rates by stage were as follows; Stage I 100% (3/3), Stage II 50% (2/4) and Stage III 22.2% (2/9). Surgery is considered the treatment of choice in this disease. However, radiation therapy may be indicated when the tumor has extended beyond the limit of surgical resections; when distant metastases are present; when the patient's general condition precludes surgery, or when surgery is refused.

  1. Results of radiation therapy for squamous cell carcinoma of vulva

    International Nuclear Information System (INIS)

    From 1962 to 1982, 20 cases of patients with squamous cell carcinoma of the vulva were treated by radiation alone at National Cancer Center Hospital, Tokyo. 80% (16/20) of these cases were over 60 years old. Treatment was made by interstitial irradiation (Radium needle or Au-Grain) and external irradiation (Betatron electron or Linac X-rays), alone or with various combinations. As for the stage of these cases, Stage I was 3 cases (15%), Stage II was 5 (25%) and Stage III was 12 (60%). Serious complications after treatment were observed in 15% (3/20) and all cases were treated with external irradiation alone. The 5 year survival rates by stage were as follows; Stage I 100% (3/3), Stage II 50% (2/4) and Stage III 22.2% (2/9). Surgery is considered the treatment of choice in this disease. However, radiation therapy may be indicated when the tumor has extended beyond the limit of surgical resections; when distant metastases are present; when the patient's general condition precludes surgery, or when surgery is refused. (author)

  2. Phagocytic cell function in response to immunosuppressive therapy.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  3. Mesenchymal stem cell-based therapy in kidney transplantation.

    Science.gov (United States)

    Chen, Cheng; Hou, Jianquan

    2016-01-01

    Kidney transplantation is the best treatment for end-stage renal disease, but its implementation is limited by organ shortage and immune rejection. Side effects of current immunosuppressive drugs, such as nephrotoxicity, opportunistic infection, and tumorigenic potential, influence long-term graft outcomes. In recent years, continued research and subsequent discoveries concerning the properties and potential utilization of mesenchymal stem cells (MSCs) have aroused considerable interest and expectations. Biological characteristics of MSCs, including multi-lineage differentiation, homing potential, paracrine effect and immunomodulation, have opened new horizons for applications in kidney transplantation. However, many studies have shown that the biological activity of MSCs depends on internal inflammatory conditions, and the safety and efficacy of the clinical application of MSCs remain controversial. This review summarizes the findings of a large number of studies and aims to provide an objective viewpoint based on a comprehensive analysis of the presently established benefits and obstacles of implementing MSC-based therapy in kidney transplantation, and to promote its clinical translation. PMID:26852923

  4. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment.

    Science.gov (United States)

    Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan; Torchilin, Vladimir P

    2016-06-01

    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types. PMID:27259361

  5. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment.

    Science.gov (United States)

    Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan; Torchilin, Vladimir P

    2016-06-01

    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types.

  6. Integration of genomics, proteomics, and imaging for cardiac stem cell therapy

    International Nuclear Information System (INIS)

    Cardiac stem cell therapy is beginning to mature as a valid treatment for heart disease. As more clinical trials utilizing stem cells emerge, it is imperative to establish the mechanisms by which stem cells confer benefit in cardiac diseases. In this paper, we review three methods - molecular cellular imaging, gene expression profiling, and proteomic analysis - that can be integrated to provide further insights into the role of this emerging therapy. (orig.)

  7. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers;

    1997-01-01

    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  8. Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

    OpenAIRE

    Meier, Daniela; Campanile, Carmen; Botter, Sander M.; Born, Walter; Fuchs, Bruno

    2014-01-01

    In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic Therapy is a novel approach for a more tumor selective treatment. Photodynamic Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon activation with light of a specific wavelength in the presence of oxygen, generates oxygen radicals that elicit a cytotoxic response(1). Despite its approval almost twenty years ago by th...

  9. Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies

    Directory of Open Access Journals (Sweden)

    Jennifer D. Stone

    2013-08-01

    Full Text Available Over the last several years, there has been considerable progress in the treatment of cancer using gene modified adoptive T cell therapies. Two approaches have been used, one involving the introduction of a conventional alpha-beta T cell receptor (TCR against a pepMHC cancer antigen, and the second involving introduction of a chimeric antigen receptor (CAR consisting of a single-chain antibody as an Fv fragment (scFv linked to transmembrane and signaling domains. In this review, we focus on one aspect of TCR-mediated adoptive T cell therapies, the impact of the affinity of the alpha-beta TCR for the pepMHC cancer antigen on both efficacy and specificity. We discuss the advantages of higher affinity TCRs in mediating potent activity of CD4 T cells. This is balanced with the potential disadvantage of higher affinity TCRs in mediating greater self-reactivity against a wider range of structurally similar antigenic peptides, especially in synergy with the CD8 co-receptor. Both TCR affinity and target selection will influence potential safety issues. We suggest pre-clinical strategies that might be used to examine each TCR for possible on-target and off-target side effects due to self-reactivities, and to adjust TCR affinities accordingly.

  10. Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Ji Woong Han

    2013-04-01

    Full Text Available Diabetic neuropathy (DN is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

  11. Myogenic Precursors from iPS Cells for Skeletal Muscle Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Isart Roca

    2015-01-01

    Full Text Available The use of adult myogenic stem cells as a cell therapy for skeletal muscle regeneration has been attempted for decades, with only moderate success. Myogenic progenitors (MP made from induced pluripotent stem cells (iPSCs are promising candidates for stem cell therapy to regenerate skeletal muscle since they allow allogenic transplantation, can be produced in large quantities, and, as compared to adult myoblasts, present more embryonic-like features and more proliferative capacity in vitro, which indicates a potential for more self-renewal and regenerative capacity in vivo. Different approaches have been described to make myogenic progenitors either by gene overexpression or by directed differentiation through culture conditions, and several myopathies have already been modeled using iPSC-MP. However, even though results in animal models have shown improvement from previous work with isolated adult myoblasts, major challenges regarding host response have to be addressed and clinically relevant transplantation protocols are lacking. Despite these challenges we are closer than we think to bringing iPSC-MP towards clinical use for treating human muscle disease and sporting injuries.

  12. Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products.

    Science.gov (United States)

    Astori, Giuseppe; Soncin, Sabrina; Lo Cicero, Viviana; Siclari, Francesco; Sürder, Daniel; Turchetto, Lucia; Soldati, Gianni; Moccetti, Tiziano

    2010-05-15

    Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cell-based therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cell-based therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cell-based medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development.

  13. GREAT PROMISE OF TISSUE-RESIDENT ADULT STEM/PROGENITOR CELLS IN TRANSPLANTATION AND CANCER THERAPIES

    OpenAIRE

    Mimeault, Murielle; Batra, Surinder K.

    2012-01-01

    Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great prom...

  14. Stem cell therapy in spinal trauma: Does it have scientific validity?

    OpenAIRE

    Harvinder Singh Chhabra; Kanchan Sarda

    2015-01-01

    Stem cell-based interventions aim to use special regenerative cells (stem cells) to facilitate neuronal function beyond the site of the injury. Many studies involving animal models of spinal cord injury (SCI) suggest that certain stem cell-based therapies may restore function after SCI. Currently, in case of spinal cord injuries, new discoveries with clinical implications have been continuously made in basic stem cell research, and stem cell-based approaches are advancing rapidly toward appli...

  15. Regulations and ethical codes for clinical cell therapy trials in Iran

    Institute of Scientific and Technical Information of China (English)

    Hooshang Saberi; Nazi Derakhshanrad; Babak Arjmand; Jafar Ai; Masoud Soleymani; Amir Ali Hamidieh; Mohammad Taghi Joghataei; Zahid Hussain Khan; Seyed Hassan Emami Razavi

    2015-01-01

    Objective:The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences with the regulations in other countries. The study reflects the latest national aspects of cell therapy in Iran and relevant regulations. Methods:The following topics are discussed in the article including sources of cell harvest, regulations for cell disposal, stem cell manufacturing, and economic aspects of stem cell, based on current practice in Iran. Results:All cell therapy trials in Iran are required to strictly abide with the ethical codes, national and local regulations, and safety requirements, as well as considering human rights and respect. Adherence to these standards has facilitated the conduct of human cell therapy trials for research, academic advancement, and therapy. Conclusions:The cell therapy trials based on the aforementioned regulations may be assumed to be ethical and they are candidates for clinical translations based on safety and efficacy issues.

  16. Two-piece hollow bulb obturator

    Directory of Open Access Journals (Sweden)

    Subramaniam Elangovan

    2011-01-01

    Full Text Available There are various types of obturator fabrication achievable by prosthodontist. Maxillectomy, which is a term used by head and neck surgeons and prosthodontists to describe the partial or total removal of the maxilla in patients suffering from benign or malignant neoplasms is a defect for which to provide an effective obturator is a difficult task for the maxillofacial prosthodontist. Multidisciplinary treatment planning is essential to achieve adequate retention and function for the prosthesis. Speech is often unintelligible as a result of the marked defects in articulation and nasal resonance. This paper describes how to achieve the goal for esthetics and phonetics and also describes the fabrication of a hollow obturator by two piece method, which is simple and maybe used as definitive obturator for maximum comfort of the patient.

  17. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  18. Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives.

    Science.gov (United States)

    Tong, Leslie M; Fong, Helen; Huang, Yadong

    2015-03-13

    Underlying cognitive declines in Alzheimer's disease (AD) are the result of neuron and neuronal process losses due to a wide range of factors. To date, all efforts to develop therapies that target specific AD-related pathways have failed in late-stage human trials. As a result, an emerging consensus in the field is that treatment of AD patients with currently available drug candidates might come too late, likely as a result of significant neuronal loss in the brain. In this regard, cell-replacement therapies, such as human embryonic stem cell- or induced pluripotent stem cell-derived neural cells, hold potential for treating AD patients. With the advent of stem cell technologies and the ability to transform these cells into different types of central nervous system neurons and glial cells, some success in stem cell therapy has been reported in animal models of AD. However, many more steps remain before stem cell therapies will be clinically feasible for AD and related disorders in humans. In this review, we will discuss current research advances in AD pathogenesis and stem cell technologies; additionally, the potential challenges and strategies for using cell-based therapies for AD and related disorders will be discussed.

  19. In Vivo Tracking of Cell Therapies for Cardiac Diseases with Nuclear Medicine

    Science.gov (United States)

    Moreira, Mayra Lorena; da Costa Medeiros, Priscylla; de Souza, Sergio Augusto Lopes; Rosado-de-Castro, Paulo Henrique

    2016-01-01

    Even though heart diseases are amongst the main causes of mortality and morbidity in the world, existing treatments are limited in restoring cardiac lesions. Cell transplantations, originally developed for the treatment of hematologic ailments, are presently being explored in preclinical and clinical trials for cardiac diseases. Nonetheless, little is known about the possible efficacy and mechanisms for these therapies and they are the center of continuous investigation. In this scenario, noninvasive imaging techniques lead to greater comprehension of cell therapies. Radiopharmaceutical cell labeling, firstly developed to track leukocytes, has been used successfully to evaluate the migration of cell therapies for myocardial diseases. A substantial rise in the amount of reports employing this methodology has taken place in the previous years. We will review the diverse radiopharmaceuticals, imaging modalities, and results of experimental and clinical studies published until now. Also, we report on current limitations and potential advances of radiopharmaceutical labeling for cell therapies in cardiac diseases. PMID:26880951

  20. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff;

    2015-01-01

    therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... the major advances in the characterization and application of TIL therapy for patients with RCC and OC....... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  1. Cell Based Therapies: At Crossroads to find the right Cell source

    Directory of Open Access Journals (Sweden)

    Editorial

    2012-01-01

    Full Text Available Development of newer Cell Based therapies for various diseases and disorders which have limited therapeutic options, is on the rise with clinical trials on cell based therapies being registered all over the world every now and then. However a dilemma arises when it comes to the choosing the ideal source of Stem cells for therapy. Clinical applications of Hematopoietic Stem cells Transplantation (HSCT in the form of Bone Marrow Transplantation has been in practice since the 1950s (1 for malignant and non malignant haematological disorders and even for auto-immune disorders (since 1977 (2, with several reports on successful outcomes after HSCT. The dilemma in HSCT is whether to use allogeneic or autologous sources. While allogeneic sources have the advantage of the graft being devoid of cancer cells, as they are from a healthy donor, they have the risk of life-long Immunosuppression. Autologous Source is advantageous as it needs no immunosuppression but the risk of relapse is high. In adult stem cells, there have been several studies which have demonstrated the various levels of safety and efficacy of both Allogeneic and autologous adult cell sources for application in diseases of the cornea, Spinal Cord, Heart, Liver etc. Each time, a study is published, the patients and the physicians are thrown into a state of perplexity on which source of cell could offer the best possible solution to the various diseases. Next hopping onto Human Embryonic Stem cells, though they were discovered in 1998, the first Human Embryonic Stem cell trial was approved by the FDA in January 2009 but it could hit the road only in October 2010 (3. The trial was for spinal cord injury and a year later, the trial came to a halt in November 2011 when the company, which was financing and pursuing the trial, announced the discontinuation of the trial due to financial reasons (4. However it is worthwhile to note that it was the financial compulsion which led to the

  2. Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development.

    Science.gov (United States)

    Ancans, Janis

    2012-01-01

    Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU.

  3. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R;

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  4. The missing piece syndrome in peer-to-peer communication

    Directory of Open Access Journals (Sweden)

    Bruce Hajek

    2011-01-01

    Full Text Available Typical protocols for peer-to-peer file sharing over the Internet divide files to be shared into pieces. New peers strive to obtain a complete collection of pieces from other peers and from a seed. In this paper we investigate a problem that can occur if the seeding rate is not large enough. The problem is that, even if the statistics of the system are symmetric in the pieces, there can be symmetry breaking, with one piece becoming very rare. If peers depart after obtaining a complete collection, they can tend to leave before helping other peers receive the rare piece. Assuming that peers arrive with no pieces, there is a single seed, random peer contacts are made, random useful pieces are downloaded, and peers depart upon receiving the complete file, the system is stable if the seeding rate (in pieces per time unit is greater than the arrival rate, and is unstable if the seeding rate is less than the arrival rate. The result persists for any piece selection policy that selects from among useful pieces, such as rarest first, and it persists with the use of network coding.

  5. Islet neogenesis potential of human adult stem cells and its applications in cell replacement therapy for diabetes

    OpenAIRE

    Bhonde RR

    2008-01-01

    In recent years regenerative biology has reached to greater heights due to its therapeutic potential in treating degenerative diseases; as they are not curable by modern medicine. With the advent of research in stem cells and developmental biology the regenerative potential of adult resident stem cells is becoming clearer. The long term objective of regenerative medicine or cell therapy is to treat patients with their own stem cells. These stem cells could be derived from the diseased organs ...

  6. A REVIEW OF GENE AND STEM CELL THERAPY IN CUTANEOUS WOUND HEALING

    OpenAIRE

    Branski, Ludwik K.; Gauglitz, Gerd G; Herndon, David N.; Jeschke, Marc G.

    2008-01-01

    Different therapies that modulate wound repair have been proposed over the last few decades. This article reviews the two emerging fields of gene and stem cell therapy in wound healing. Gene therapy, initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have showed the most potential. The majority of gene delivery systems are based on viral transfection, naked DN...

  7. Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Andrea Farini

    2014-01-01

    Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

  8. Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pattani, Varun P., E-mail: varun.pattani@utexas.edu; Shah, Jay; Atalis, Alexandra; Sharma, Anirudh; Tunnell, James W. [The University of Texas at Austin, Department of Biomedical Engineering (United States)

    2015-01-15

    Current cancer therapies can cause significant collateral damage due to a lack of specificity and sensitivity. Therefore, we explored the cell death pathway response to gold nanorod (GNR)-mediated photothermal therapy as a highly specific cancer therapeutic to understand the role of apoptosis and necrosis during intense localized heating. By developing this, we can optimize photothermal therapy to induce a maximum of ‘clean’ cell death pathways, namely apoptosis, thereby reducing external damage. GNRs were targeted to several subcellular localizations within colorectal tumor cells in vitro, and the cell death pathways were quantitatively analyzed after photothermal therapy using flow cytometry. In this study, we found that the cell death response to photothermal therapy was dependent on the GNR localization. Furthermore, we demonstrated that nanorods targeted to the perinuclear region irradiated at 37.5 W/cm{sup 2} laser fluence rate led to maximum cell destruction with the ‘cleaner’ method of apoptosis, at similar percentages as other anti-cancer targeted therapies. We believe that this indicates the therapeutic potential for GNR-mediated photothermal therapy to treat cancer effectively without causing damage to surrounding tissue.

  9. Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration

    Directory of Open Access Journals (Sweden)

    Maximiliano I. Schaun

    2016-01-01

    Full Text Available The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair.

  10. A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

    International Nuclear Information System (INIS)

    Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24−/CD44+) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies. This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer

  11. A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yu Kyeong; Lee, Jae Ho; Park, Ga-Young; Chun, Sung Hak; Han, Jeong Yun; Kim, Sung Dae [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Lee, Janet [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Suwon, Gyeonggi 440-746 (Korea, Republic of); Yang, Kwangmo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Lee, Chang Geun, E-mail: cglee@dirams.re.kr [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of)

    2013-01-25

    Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24{sup −}/CD44{sup +}) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies. This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer.

  12. Therapy effects of gold nanorods on the CNE-1 nasopharyngeal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Shao J

    2012-10-01

    Full Text Available Jinyan Shao,1 Jianguo Tang,1 Jian Ji,2 Wenbo Zhou21Department of Otolaryngology, Head and Neck Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 2Department of Polymer Science, Ministry of Education Key Laboratory of Macromolecule Synthesis and Functionalization, Zhejiang University, Hangzhou, People's Republic of ChinaAbstract: The use of nanocarriers to deliver drugs to tumor tissue is one of the most important strategies in cancer therapeutics. Recently, gold nanorods (GNRs have begun to be used in cancer therapy because of their unique properties. The purpose of this study was to show the potential that GNRs have against human nasopharyngeal carcinoma CNE-1 cells, using near-infrared (NIR laser light. Transmission electron microscopic and ultraviolet-visible spectroscopic investigations confirmed the efficient uptake of the GNRs by CNE-1 and human rhinal epithelia cells. The in vitro NIR photothermal therapy for the CNE-1 and rhinal epithelia cells was designed in three groups: (1 control, (2 laser alone, and (3 GNRs with laser. Fluorescence microscopy images indicated that, at some GNR concentrations and some intensities of NIR laser, GNRs with laser therapy could induce cell death for CNE-1 cells while keeping the rhinal epithelia cells healthy. Therefore, the results of this study suggest that using GNRs with NIR laser therapy can selectively destruct CNE-1 cells while having no effect on normal (rhinal epithelia cells.Keywords: photothermal therapy, near-infrared laser, rhinal epithelia cells, cell uptake

  13. Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure.

    Science.gov (United States)

    Hashemi Goradel, Nasser; Darabi, Masoud; Shamsasenjan, Karim; Ejtehadifar, Mostafa; Zahedi, Sarah

    2015-09-01

    Cell therapy is a promising intervention for treating liver diseases and liver failure. Different animal models of human liver cell therapy have been developed in recent years. Rats and mice are the most commonly used liver failure models. In fact, rodent models of hepatic failure have shown significant improvement in liver function after cell infusion. With the advent of stem-cell technologies, it is now possible to re-programme adult somatic cells such as skin or hair-follicle cells from individual patients to stem-like cells and differentiate them into liver cells. Such regenerative stem cells are highly promising in the personalization of cell therapy. The present review article will summarize current approaches to liver stem cell therapy with rodent models. In addition, we discuss common cell tracking techniques and how tracking data help to direct liver cell therapy research in animal models of hepatic failure.

  14. Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy.

    Science.gov (United States)

    Duret, Cedric; Moreno, Daniel; Balasiddaiah, Anangi; Roux, Solene; Briolotti, Phillipe; Raulet, Edith; Herrero, Astrid; Ramet, Helene; Biron-Andreani, Christine; Gerbal-Chaloin, Sabine; Ramos, Jeanne; Navarro, Francis; Hardwigsen, Jean; Maurel, Patrick; Aldabe, Rafael; Daujat-Chavanieu, Martine

    2015-01-01

    Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation. PMID:25622096

  15. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  16. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  17. An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy

    DEFF Research Database (Denmark)

    Bach, Lars Arve; Bentzen, Søren; Alsner, Jan;

    2001-01-01

    interpretations of gene therapy. Two prototypical strategies for gene therapy are suggested, both of them leading to extinction of the malignant phenotype: one approach would be to reduce the relative proportion of the cooperating malignant cell type below a certain critical value. Another approach would...

  18. Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; zbr735, zbr735; Iversen, Lars;

    2015-01-01

    PURPOSE: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments...

  19. Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2015-11-01

    Full Text Available Embryonic development and carcinogenesis share many molecular pathways and regulatory molecules. While the induction of a pluripotent state involves a significant oncogenic risk, as in induced pluripotent stem cells (iPSCs, the embryonic environment in vivo has been shown to suppress tumor development. In this review, we discuss the subtle equilibrium between the nanotopography (niche of the hosting tissue resident stem cells and their biological dynamics, including the transformation in cancer stem cells. We review consistent findings indicating the potential for modulating the biology of human cancer stem cells by the aid of naturally occurring or synthetic molecules, including developmental stage zebrafish embryo extracts, hyaluronan, butyric acid (BA and retinoic acid (RA, hyaluronan mixed esters of BA and RA, melatonin, vitamin D3, and endorphin peptides. Within this context, we dissect the multifaceted mechanisms orchestrated by endorphinergic systems, including paracrine cellto- cell communication, as well as the establishment of autocrine and intracrine (intracellular peptide actions driving transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of differentiation, growth regulation and cell memory. Based upon the remarkable action of electromagnetic fields and mechanical vibration on (stem cell signaling, differentiation, and senescence, we also consider the potential for using these physical energies as a tool to afford a fine tuning of cancer stem cell fate. On the whole, we forecast future deployment of the physical and/or chemical approaches described herein aiming at reprogramming, rather than destroying cancer stem cells, eventually placing cancer therapy within the context of Regenerative Medicine.

  20. Colorectal cancer stem cells : regulation of the phenotype and implications for therapy resistance

    NARCIS (Netherlands)

    Emmink, B.L.

    2014-01-01

    In this thesis different aspects of cancer stem cells in colorectal cancer are discribed. We focus on the therapy resistance of cancer stem cells and the effect that reactive oxygen species and hypoxia have on the cancer stem cell phenotype. For this purpose a novel culture method to propagate cance

  1. Enabling stem cell therapies through synthetic stem cell–niche engineering

    OpenAIRE

    Peerani, Raheem; Zandstra, Peter W.

    2010-01-01

    Enabling stem cell–targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be u...

  2. Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy

    Directory of Open Access Journals (Sweden)

    Ulrike Baranyi

    2016-05-01

    Conclusion: This proof-of-concept study demonstrates that allergen-specific immunological tolerance preventing occurrence of allergy can be established through a cell-based therapy employing allergen-expressing leukocytes.

  3. Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis

    Science.gov (United States)

    Li, Mingchao; Li, Hao; Ruan, Yajun; Wang, Tao; Liu, Jihong

    2016-01-01

    Introduction Stem cell therapy is a novel method for the treatment of diabetic erectile dysfunction (ED). Many relative animal studies have been done to evaluate the efficacy of this therapy in rats. Aims This meta-analysis was performed to compare the efficacy of different stem cell therapies, to evaluate the influential factors and to determine the optimal stem cell therapeutic strategy for diabetic ED. Methods We searched the studies analyzing the efficacy of stem cell therapy for diabetic ED in rats published before September 30, 2015 in PubMed, Web of Science and EBSCO. A random effects meta-analysis was conducted to assess the outcomes of stem cell therapy. Subgroup analysis was also performed by separating these studies based on their different characteristics. Changes in the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP) and in the structure of the cavernous body were compared. Results 10 studies with 302 rats were enrolled in this meta-analysis. Pooled analysis of these studies showed a beneficial effect of stem cell therapy in improving erectile function of diabetic rats (SMD 4.03, 95% CI = 3.22 to 4.84, P< 0.001). In the stem cell therapy group, both the smooth muscle and endothelium content were much more than those in control group. There was also significant increase in the expression of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS), the ratio of smooth muscle to collagen, as well as the secretion of vascular endothelial growth factor (VEGF). Besides, apoptotic cells were reduced by stem cell treatment. The subgroup analysis indicated that modified stem cells were more effective than those without modification. Conclusions Our results confirmed that stem cell therapy could apparently improve the erectile function of diabetic rats. Some specific modification, especially the gene modification with growth factors, could improve the efficacy of stem cell therapy. Stem cell therapy has potential

  4. Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mingchao Li

    Full Text Available Stem cell therapy is a novel method for the treatment of diabetic erectile dysfunction (ED. Many relative animal studies have been done to evaluate the efficacy of this therapy in rats.This meta-analysis was performed to compare the efficacy of different stem cell therapies, to evaluate the influential factors and to determine the optimal stem cell therapeutic strategy for diabetic ED.We searched the studies analyzing the efficacy of stem cell therapy for diabetic ED in rats published before September 30, 2015 in PubMed, Web of Science and EBSCO. A random effects meta-analysis was conducted to assess the outcomes of stem cell therapy. Subgroup analysis was also performed by separating these studies based on their different characteristics. Changes in the ratio of intracavernous pressure (ICP to mean arterial pressure (MAP and in the structure of the cavernous body were compared.10 studies with 302 rats were enrolled in this meta-analysis. Pooled analysis of these studies showed a beneficial effect of stem cell therapy in improving erectile function of diabetic rats (SMD 4.03, 95% CI = 3.22 to 4.84, P< 0.001. In the stem cell therapy group, both the smooth muscle and endothelium content were much more than those in control group. There was also significant increase in the expression of endothelial nitric oxide synthase (eNOS and neuronal nitric oxide synthase (nNOS, the ratio of smooth muscle to collagen, as well as the secretion of vascular endothelial growth factor (VEGF. Besides, apoptotic cells were reduced by stem cell treatment. The subgroup analysis indicated that modified stem cells were more effective than those without modification.Our results confirmed that stem cell therapy could apparently improve the erectile function of diabetic rats. Some specific modification, especially the gene modification with growth factors, could improve the efficacy of stem cell therapy. Stem cell therapy has potential to be an effective therapeutic

  5. Stem cell-based therapies for tumors in the brain: are we there yet?

    Science.gov (United States)

    Shah, Khalid

    2016-08-01

    Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. PMID:27282399

  6. [Cell-based therapies - an innovative therapeutic option in ophthalmology: Treating corneal diseases with stem cells].

    Science.gov (United States)

    Bakker, Ann-Christin; Langer, Barbara

    2015-11-01

    Pathological changes and disorders of the cornea are a major cause of severe visual impairment and blindness. Replacement of a pathologically altered cornea with healthy corneal tissue from the eye of a suitable donor is among the most common and successful transplantation procedures in medicine. In Germany, approximately 5000-6000 corneal transplantations are performed each year, but the total demand per year is estimated to be twice as high. With a success rate of 90%, the outcome of cornea transplantation is very favourable. However, long-term maintenance and regeneration of a healthy new cornea requires tissue-specific corneal stem cells residing at the basal layer of the limbus, which is the annular transition zone between the cornea and sclera. When this important limbal stem cell population is destroyed or dysfunctional, a pathological condition known as limbal stem cell deficiency (LSCD) manifests. Limbal stem cell deficiency describes conditions associated with impaired corneal wound healing and regeneration. In this situation, transplantation of healthy limbal stem cells is the only curative treatment approach for restoration of an intact and functional ocular surface. To date, treatment of LSCD presents a great challenge for ophthalmologists. However, innovative, cell-therapeutic approaches may open new, promising treatment perspectives. In February 2015, the European Commission granted marketing authorization to the first stem cell-based treatment in the European Union. The product named Holoclar® is an advanced therapy medicinal product (ATMP) for the treatment of moderate to severe LSCD due to physical and chemical burns in adults. Further cell-based treatment approaches are in clinical development. PMID:26459569

  7. Dramatic and sustained responsiveness of pulmonary Langerhans cell histiocytosis-associated pulmonary hypertension to vasodilator therapy

    OpenAIRE

    Adam May; Garvan Kane; Eunhee Yi; Robert Frantz; Robert Vassallo

    2015-01-01

    Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon diffuse lung disease characterized by the abnormal accumulation of Langerhans' cells around small airways and other distal lung compartments. Although pulmonary hypertension (PH) is a frequent complication of PLCH, the role of advanced PH therapies for PLCH-related PH is not well-established. We describe a PLCH patient with severe, disease-related PH that responded unexpectedly well to advanced PH therapy with sustained improvement...

  8. Concise Review: Clinical Translation of Wound Healing Therapies Based on Mesenchymal Stem Cells

    OpenAIRE

    Jackson, Wesley M.; Nesti, Leon J.; Tuan, Rocky S.

    2011-01-01

    There is enormous worldwide demand for therapies to promote the efficient resolution of hard-to-heal wounds with minimal appearance of scarring. Recent in vitro studies with mesenchymal stem cells (MSCs) have identified numerous mechanisms by which these cells can promote the process of wound healing, and there is significant interest in the clinical translation of an MSC-based therapy to promote dermal regeneration. This review provides a systematic analysis of recent preclinical and clinica...

  9. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Peter J Nelson; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  10. Cell therapy to remove excess copper in Wilson’s disease

    OpenAIRE

    Gupta, Sanjeev

    2014-01-01

    To achieve permanent correction of Wilson’s disease by a cell therapy approach, replacement of healthy hepatocytes will be most desirable. There is a physiological need for hepatic ATP7B-dependent copper transport in bile, which is deficient in Wilson’s disease, producing progressive copper accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raised possibilities for cell therapy in Wilson’s disease. Therapeutic principles included...

  11. Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

    Science.gov (United States)

    Pashoutan Sarvar, Davod; Shamsasenjan, Karim; Akbarzadehlaleh, Parvin

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell-to-cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC-derived exosomes (MSC-DEs) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC-DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs. They have the supportive functions in organisms such as repairing tissue damages, suppressing inflammatory responses, and modulating the immune system. MSC-DEs are of great interest in the scope of regenerative medicine because of their unique capacity to the regeneration of the damaged tissues, and the present paper aims to introduce MSC-DEs as a novel hope in cell-free therapy.

  12. Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity.

    Science.gov (United States)

    Cho, Seung-Ju; Kim, So-Yeon; Jeong, Ho-Chang; Cheong, Hyeonsik; Kim, Doseok; Park, Soon-Jung; Choi, Jong-Jin; Kim, Hyongbum; Chung, Hyung-Min; Moon, Sung-Hwan; Cha, Hyuk-Jin

    2015-12-01

    Stem-toxic small molecules have been developed to induce selective cell death of pluripotent stem cells (PSCs) to lower the risk of teratoma formation. However, despite their high efficacies, chemical-based approaches may carry unexpected toxicities on specific differentiated cell types. Herein, we took advantage of KillerRed (KR) as a suicide gene, to selectively induce phototoxicity using visible light via the production of reactive oxygen species. PSCs in an undifferentiated state that exclusively expressed KR (KR-PSCs) were eliminated by a single exposure to visible light. This highly selective cell death in KR-PSCs was exploited to successfully inhibit teratoma formation. In particular, endothelial cells from KR-mPSCs remained fully functional in vitro and sufficient to repair ischemic injury in vivo regardless of light exposure, suggesting that a genetic approach in which KR is expressed in a tightly controlled manner would be a viable strategy to inhibit teratoma formation for future safe PSC-based therapies.

  13. Blastic Plasmacytoid Dendritic Cell Neoplasm: From Origin of the Cell to Targeted Therapies.

    Science.gov (United States)

    Laribi, Kamel; Denizon, Nathalie; Besançon, Anne; Farhi, Jonathan; Lemaire, Pierre; Sandrini, Jeremy; Truong, Catherine; Ghnaya, Habib; Baugier de Materre, Alix

    2016-08-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid dendritic cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics. PMID:27026248

  14. Impact of additives on corrosion rate of cans filled with pieces of apricot

    Directory of Open Access Journals (Sweden)

    Tošković D.V.

    2005-01-01

    Full Text Available Polarization techniques are used for testing the impact of different compounds (additives on tinplate corrosion, using pieces of apricot dipped in syrup with and without nitrate addition as electrolyte solution, at the same time using filled cans as electrolytic cell and operating electrode. This procedure determined the intensity of inhibiting tin dissolving with some of the used additives like sodium-benzoate, potassium-sorbate sodium-lauril-sulphate and p-aminobenzoate acid. Adding these additives to canned pieces of apricot in syrup led to inhibiting of tin dissolving, which was experimentally proved.

  15. Free Seifert pieces of pseudo-Anosov flows

    OpenAIRE

    Barbot, Thierry; Fenley, Sergio

    2015-01-01

    We prove a structure theorem for pseudo-Anosov flows restricted to Seifert fibered pieces of three manifolds. The piece is called periodic if there is a Seifert fibration so that a regular fiber is freely homotopic, up to powers, to a closed orbit of the flow. A non periodic Seifert fibered piece is called free. In a previous paper [Ba-Fe1] we described the structure of a pseudo-Anosov flow restricted to a periodic piece up to isotopy along the flow. In the present paper we consider free Seif...

  16. Effect of low level laser therapy and high intensity laser therapy on endothelial cell proliferation in vitro: preliminary communication

    Science.gov (United States)

    Lukowicz, Malgorzata; Szymanska, Justyna; Goralczyk, Krzysztof; Zajac, Andrzej; Rość, Danuta

    2013-01-01

    Background: The main purpose of this study was to analyze the influence of power intensity and wavelength of Low Level Laser Therapy (LLLT) and HILT (High Intensity Laser Therapy) on endothelial cell proliferation. Material and methods: The tests were done on human umbilical vein endothelial cells (HUVEC). Cultures were exposed to laser irradiation of 660 nm and 670 nm at different dosages, power output was 10 - 40 mW as well as 820 nm with power 100 mW and 808 nm with power 1500 mW. Energy density was from 0.28 to 11,43 J/cm2. Cell proliferation of a control and tested culture was evaluated with a colorimetric device to detect live cells. The tests were repeated 8 times. Results: We observed good effects of LLLT on live isolated ECs and no effects in experiments on previous deep-frozen cultures. Also HILT stimulated the proliferation of HUVEC. Conclusion: Endothelial cells play a key role in vascular homeostasis in humans. We observed the stimulatory effect of LLLT and HILT on proliferation of HUVEC. Many factors influence the proliferation of EC, so is it necessary to continue the experiment with different doses, intensity and cell concentration.

  17. Terapia celular da pseudoartose Cell therapy of pseudarthrosis

    Directory of Open Access Journals (Sweden)

    Ricardo Bastos Filho

    2012-01-01

    Full Text Available OBJETIVO: Analisar a segurança e a eficácia da infusão percutânea no foco da pseudoartrose do aspirado de medula óssea total e da infusão de células mononucleares purificadas e concentradas. MÉTODOS: Foram tratados seis pacientes portadores de pseudoartrose de tíbia ou de fêmur. Quatro receberam infusão do aspirado de medula óssea autóloga total obtida da crista ilíaca e dois receberam o aspirado de medula óssea autóloga processada com Sepax®. Não foi alterado o método de fixação primária ou exposto o foco da pseudoartrose. Realizou-se exame físico e avaliação radiográfica 2, 4 e 6 meses após o procedimento. Após a consolidação, foi avaliado o grau de satisfação do paciente. RESULTADOS: Não verificamos qualquer complicação decorrente dos procedimentos. No primeiro grupo (aspirado total a consolidação foi obtida entre três e vinte e quatro semanas e, no segundo grupo (Sepax®, entre 12 e 16 semanas. O grau de satisfação dos pacientes teve a média aumentada de 2,75 para 9 no grupo I e de 1 para 8,5 no grupo II (p=0,0156. CONCLUSÃO: Concluímos que o tratamento das pseudoartroses com os métodos avaliados mostraram-se eficazes e seguros independente do método de estabilização utilizado. Nível de Evidência II, Estudo Prospectivo Comparativo.OBJECTIVE: To assess the safety and efficiency of cell therapy for pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear cells purified extemporaneously using the Sepax® equipment. METHODS: Six patients with nonunion of the tibia or femur were treated. Four received a percutaneous infusion of autologous bone marrow aspirated from the iliac crest, and two received autologous bone marrow mononuclear cells separated from the aspirate with the Sepax®. The primary fixation method was unchanged, and the nonunion focus was not exposed. Physical examination and radiographies were performed 2, 4 and 6 months after the treatment by the same

  18. The last piece of the ring

    CERN Multimedia

    2008-01-01

    In a sequel to the recent success at CMS, the last section of the LHC beam vacuum system was installed in ATLAS on Monday 16 June. The place where experiment and accelerator meet, the completion of the last part of the continuous 27 km beampipe signals how near the LHC is to the circulation of its first beam. Watch the video! The last section of the LHC beampipe being installed in ATLAS.Although a seemingly simple piece of technology in comparison with the complexity of the detectors, the beampipe is a carefully designed and essential part of both the experiments and the LHC. The section of beam pipe that completed the LHC ring on Monday 16 June is about 20 metres from the centre of ATLAS, very close to where the first magnets of the LHC are located. Unlike the central ATLAS beampipe, which is made of beryllium, the final section is made of stainless steel. An aluminium cone surrounds the stainless steel tube with the super slim...

  19. Model Checking in Bits and Pieces

    Directory of Open Access Journals (Sweden)

    Kedar S. Namjoshi

    2013-09-01

    Full Text Available Fully automated verification of concurrent programs is a difficult problem, primarily because of state explosion: the exponential growth of a program state space with the number of its concurrently active components. It is natural to apply a divide and conquer strategy to ameliorate state explosion, by analyzing only a single component at a time. We show that this strategy leads to the notion of a "split" invariant, an assertion which is globally inductive, while being structured as the conjunction of a number of local, per-component invariants. This formulation is closely connected to the classical Owicki-Gries method and to Rely-Guarantee reasoning. We show how the division of an invariant into a number of pieces with limited scope makes it possible to apply new, localized forms of symmetry and abstraction to drastically simplify its computation. Split invariance also has interesting connections to parametric verification. A quantified invariant for a parametric system is a split invariant for every instance. We show how it is possible, in some cases, to invert this connection, and to automatically generalize from a split invariant for a small instance of a system to a quantified invariant which holds for the entire family of instances.

  20. Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies.

    Science.gov (United States)

    Rennert, Robert C; Januszyk, Michael; Sorkin, Michael; Rodrigues, Melanie; Maan, Zeshaan N; Duscher, Dominik; Whittam, Alexander J; Kosaraju, Revanth; Chung, Michael T; Paik, Kevin; Li, Alexander Y; Findlay, Michael; Glotzbach, Jason P; Butte, Atul J; Gurtner, Geoffrey C

    2016-01-01

    Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application. PMID:27324848

  1. Small DNA pieces in C. elegans are intermediates of DNA fragmentation during apoptosis.

    Directory of Open Access Journals (Sweden)

    P Joseph Aruscavage

    Full Text Available While studying small noncoding RNA in C. elegans, we discovered that protocols used for isolation of RNA are contaminated with small DNA pieces. After electrophoresis on a denaturing gel, the DNA fragments appear as a ladder of bands, approximately 10 nucleotides apart, mimicking the pattern of nuclease digestion of DNA wrapped around a nucleosome. Here we show that the small DNA pieces are products of the DNA fragmentation that occurs during apoptosis, and correspondingly, are absent in mutant strains incapable of apoptosis. In contrast, the small DNA pieces are present in strains defective for the engulfment process of apoptosis, suggesting they are produced in the dying cell prior to engulfment. While the small DNA pieces are also present in a number of strains with mutations in predicted nucleases, they are undetectable in strains containing mutations in nuc-1, which encodes a DNase II endonuclease. We find that the small DNA pieces can be labeled with terminal deoxynucleotidyltransferase only after phosphatase treatment, as expected if they are products of DNase II cleavage, which generates a 3' phosphate. Our studies reveal a previously unknown intermediate in the process of apoptotic DNA fragmentation and thus bring us closer to defining this important pathway.

  2. Potential for cell therapy in Parkinson's disease using genetically programmed human embryonic stem cell-derived neural progenitor cells.

    Science.gov (United States)

    Ambasudhan, Rajesh; Dolatabadi, Nima; Nutter, Anthony; Masliah, Eliezer; Mckercher, Scott R; Lipton, Stuart A

    2014-08-15

    Neural transplantation is a promising strategy for restoring dopaminergic dysfunction and modifying disease progression in Parkinson's disease (PD). Human embryonic stem cells (hESCs) are a potential resource in this regard because of their ability to provide a virtually limitless supply of homogenous dopaminergic progenitors and neurons of appropriate lineage. The recent advances in developing robust cell culture protocols for directed differentiation of hESCs to near pure populations of ventral mesencephalic (A9-type) dopaminergic neurons has heightened the prospects for PD cell therapy. Here, we focus our review on current state-of-the-art techniques for harnessing hESC-based strategies toward development of a stem cell therapeutic for PD. Importantly, we also briefly describe a novel genetic-programming approach that may address many of the key challenges that remain in the field and that may hasten clinical translation.

  3. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    Directory of Open Access Journals (Sweden)

    P Kasten

    2008-10-01

    Full Text Available In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM, clusters of differentiation (CD, proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years. The number of colony forming units-fibroblast (CFU-F/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant, the centrifuge Ficoll (p=0.042 and the manual Ficoll procedure (p=0.001. The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5 with 297 ml BM (SD 18.6, the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 102 MSC/ml BM (standard deviation (SD 1.02 x 102 before concentration, 14.8 x 102 MSC/ ml BM (SD 12.4 x 102 after concentration, and on average 296 x 102 MSC (SD 248.9 x 102, range 86.4-691.5 x 102 were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.

  4. Stem cell therapies in preclinical models of stroke associated with aging

    Directory of Open Access Journals (Sweden)

    Aurel ePopa-Wagner

    2014-11-01

    Full Text Available Stroke has limited treatment options, demanding a vigorous search for new therapeutic strategies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments related to unfavorable environments that are in part related to aging processes. Since stroke afflicts mostly the elderly, it is highly desirable and clinically important to test the efficacy of cell therapies in aged brain microenvironments. Although widely believed to be refractory to regeneration, recent studies using both neural precursor cells and bone marrow-derived mesenchymal stem cells for stroke therapy suggest that the aged rat brain is not refractory to cell-based therapy, and that it also supports plasticity and remodeling. Yet, important differences exist in the aged compared with young brain, i.e., the accelerated progression of ischemic injury to brain infarction, the reduced rate of endogenous neurogenesis and the delayed initiation of neurological recovery. Pitfalls in the development of cell-based therapies may also be related to age-associated comorbidities, e.g., diabetes or hyperlipidemia, which may result in maladaptive or compromised brain remodeling, respectively. These age-related aspects should be carefully considered in the clinical translation of restorative therapies.

  5. Ambivalent journeys of hope: embryonic stem cell therapy in a clinic in India.

    Science.gov (United States)

    Prasad, Amit

    2015-03-01

    Stem cell therapy in non-Western countries such as India has received a lot of attention. Apart from media reports, there are a number of social science analyses of stem cell policy, therapy, and research, their ethical implications, and impact of advertising on patients. Nevertheless, in the media reports as well as in academic studies, experiences of patients, who undertake overseas journeys for stem cell therapy, have largely been either ignored or presented reductively, often as a "false hope." In this article, I analyze the experiences of patients and their "journeys of hope" to NuTech Mediworld, an embryonic stem cell therapy clinic in New Delhi, India. My analysis, which draws on my observations in the clinic and patients' experiences, instead of seeking to adjudicate whether embryonic stem cell therapy in clinics such as NuTech is right or wrong, true or false, focuses on how patients navigate and contest these concerns. I utilize Gilles Deleuze and Felix Guattari's "concepts," lines of flight and deterritorialization, to highlight how embryonic stem cell therapy's "political economy of hope" embodies deterritorialization of several "regimes of truth" and how these deterritorializations impact patients' experiences.

  6. Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

    Directory of Open Access Journals (Sweden)

    Shujing Shi

    Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

  7. Combining Antiangiogenic Therapy with Adoptive Cell Immunotherapy Exerts Better Antitumor Effects in Non-Small Cell Lung Cancer Models

    Science.gov (United States)

    Shi, Shujing; Wang, Rui; Chen, Yitian; Song, Haizhu; Chen, Longbang; Huang, Guichun

    2013-01-01

    Introduction Cytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. Methods We combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. Results Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. Conclusions Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung

  8. Cell Therapy for Stroke: Review of Previous Clinical Trials and Introduction of Our New Trials

    Science.gov (United States)

    SHICHINOHE, Hideo; HOUKIN, Kiyohiro

    2016-01-01

    Stroke is still a leading cause of death and disability, and despite intensive research, few treatment options exist. A recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Although some pioneer studies on the use of cell therapy for the treatment of stroke have been reported, certain problems still remain unsolved. We investigated the use of autologous bone marrow stromal cell (BMSC) transplantation for the treatment of stroke, to develop it as the next-generation cell therapy. In this study, we introduce the preparation of a new clinical trial, the Research on Advanced Intervention using Novel Bone marrow stem cell (RAINBOW) study. The trial will start in 2016, and we hope that it will not only be helpful for treating patients but also for clarifying the therapeutic mechanisms. Moreover, we review stem cell therapeutics as an emerging paradigm in stroke (STEPS) and the guidelines for the development of cell therapy for stroke in the United States as well as introduce the development of new guidelines in Japan. These guidelines are expected to encourage the development of cell therapy for stroke management. PMID:27302193

  9. Chimeric antigen receptor T cell therapy: 25years in the making.

    Science.gov (United States)

    Gill, Saar; Maus, Marcela V; Porter, David L

    2016-05-01

    Chimeric antigen receptor (CAR) T cell therapy of cancer is generating enormous enthusiasm. Twenty-five years after the concept was first proposed, major advances in molecular biology, virology, and good manufacturing practices (GMP)-grade cell production have transformed antibody-T cell chimeras from a scientific curiosity to a fact of life for academic cellular immunotherapy researchers and, increasingly, for patients. In this review, we explain the preclinical concept, outline how it has been translated to the clinic, and draw lessons from the first years of CAR T cell therapy for the practicing clinician. PMID:26574053

  10. Stem cell therapy for white matter disorders: don't forget the microenvironment!

    Science.gov (United States)

    Dooves, Stephanie; van der Knaap, Marjo S; Heine, Vivi M

    2016-07-01

    White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in rodent disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial. PMID:27000179

  11. Test of critical steps towards a combined cell and gene therapy approach for the treatment of Duchenne muscular dystrophy

    DEFF Research Database (Denmark)

    Kajhøj, Tine Qvistgaard; Duch, Mogens R.; Pedersen, Finn Skou;

    2015-01-01

    Background: Therapies for muscular dystrophies remain a major challenge in spite of advanced strategies using either cell or gene therapy. We here propose a combined approach of cell and gene therapy. As gene delivery vehicles with specific homing potential we have chosen mesoangioblasts which...

  12. Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Demizu

    2014-01-01

    Full Text Available Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT, proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

  13. Cells therapy for Parkinson’s disease-so close and so far away

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    One of the strategies of treating Parkinson’s disease(PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells.Potential sources for cells range from autologous grafts of dopamine secreting cells,fetal ventral mesencephalon tissue,to various stem cell types.Over the past quarter century,many experimental replacement therapies have been tried on PD animal models as well as human patients,yet none resulted in satisfactory outcomes that warrant wide applications.Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells(ntES) or induced pluripotent stem cells(iPS) derived cells can be used to successfully treat rodent PD models,thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PD.Meanwhile,however,post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area,indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain.A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson’s disease.It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.

  14. Cells therapy for Parkinson's disease-so close and so far away

    Institute of Scientific and Technical Information of China (English)

    REN ZhenHua; ZHANG Yu

    2009-01-01

    One of the strategies of treating Parkinson's disease (PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells. Potential sources for cells range from autologous grafts of dopamine secreting cells, fetal ventral mesencephalon tissue, to various stem cell types. Over the past quarter century, many experimental replacement therapies have been tried on PD animal models as well as human patients, yet none resulted in satisfactory outcomes that warrant wide applications. Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells (ntES) or induced pluripotent stem cells (iPS) derived cells can be used to successfully treat rodent PO models, thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PO. Meanwhile, however, post mortem analysis of patients who fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area, indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain. A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson's disease.It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.

  15. Cytokine-induced killer (CIK cell therapy for patients with hepatocellular carcinoma: efficacy and safety

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2012-04-01

    Full Text Available Abstract Purpose To evaluate the efficacy of cytokine-induced killer (CIK cell therapy in the treatment of hepatocellular carcinoma. Materials and methods Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Results The analysis showed significant survival benefit (one-year survival, p p p p p p +, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p Conclusions CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.

  16. Spatial and Temporal Measurements of Temperature and Cell Viability in Response to Nanoparticle Mediated Photothermal Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Whitney, Jon R [ORNL; Rodgers, Amanda [Virginia Polytechnic Institute and State University; Harvie, Erica [Virginia Polytechnic Institute and State University; Carswell, William [Virginia Polytechnic Institute and State University; Torti, Suzy [Wake Forest University, Winston-Salem; Puretzky, Alexander A [ORNL; Rouleau, Christopher M [ORNL; Geohegan, David B [ORNL; Rylander, Christopher [Virginia Polytechnic Institute and State University; Rylander, Nichole M [Virginia Polytechnic Institute and State University

    2012-01-01

    Aim: Nanoparticle enhanced photothermal therapy is a promising alternative to tumor resection. However, quantitative measurements of cellular response to these treatments are limited. This paper introduces a Bimodal Enhanced Analysis of Spatiotemporal Temperature (BEAST) algorithm to rapidly determine the viability of cancer cells in vitro following photothermal therapy alone or in combination with nanoparticles. Materials & Methods: To illustrate the capability of the BEAST viability algorithm, single wall carbon nanohorns were added to renal cancer (RENCA) cells in vitro and time-dependent spatial temperature maps measured with an infrared camera during laser therapy were correlated with post-treatment cell viability distribution maps obtained by cell-staining fluorescent microscopy. Conclusion: The BEAST viability algorithm accurately and rapidly determined the cell viability as function of time, space, and temperature.

  17. Complex PTSD and phased treatment in refugees: a debate piece

    Directory of Open Access Journals (Sweden)

    F. Jackie June ter Heide

    2016-02-01

    Full Text Available Background: Asylum seekers and refugees have been claimed to be at increased risk of developing complex posttraumatic stress disorder (complex PTSD. Consequently, it has been recommended that refugees be treated with present-centred or phased treatment rather than stand-alone trauma-focused treatment. This recommendation has contributed to a clinical practice of delaying or waiving trauma-focused treatment in refugees with PTSD. Objective: The aim of this debate piece is to defend two theses: (1 that complex trauma leads to complex PTSD in a minority of refugees only and (2 that trauma-focused treatment should be offered to all refugees who seek treatment for PTSD. Methods: The first thesis is defended by comparing data on the prevalence of complex PTSD in refugees to those in other trauma-exposed populations, using studies derived from a systematic review. The second thesis is defended using conclusions of systematic reviews and a meta-analysis of the efficacy of psychotherapeutic treatment in refugees. Results: Research shows that refugees are more likely to meet a regular PTSD diagnosis or no diagnosis than a complex PTSD diagnosis and that prevalence of complex PTSD in refugees is relatively low compared to that in survivors of childhood trauma. Effect sizes for trauma-focused treatment in refugees, especially narrative exposure therapy (NET and culturally adapted cognitive-behaviour therapy (CA-CBT, have consistently been found to be high. Conclusions: Complex PTSD in refugees should not be assumed to be present on the basis of complex traumatic experiences but should be carefully diagnosed using a validated interview. In line with treatment guidelines for PTSD, a course of trauma-focused treatment should be offered to all refugees seeking treatment for PTSD, including asylum seekers.

  18. Progress of Gene-Modified Hematopoietic Stem Cell Therapy For Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Atil Bisgin

    2014-02-01

    Full Text Available Sickle cell disease and β-thalassemia represent the most common forms of hemoglobinopathies. Since the first successful bone marrow transplant in 1981, hematopoietic stem cell transplantation is the only treatment option for the patients. However, the current routine therapies for these conditions are limited by the availability of suitable donors and graft-vs-host disease. On the other hand, hemoglobinopathies were long considered amenable to the genetic correction by available gene transfer technologies. Therefore, gene therapy strategies aim at the globin gene transfer resulting hemoglobin function recovery. Here we review the studies and clinical applications of gene therapy for the hemoglobinopathies within the timeline of developed technologies, including the viral vectors, transposons, homolog recombination as a treatment modality together with generation of induced pluripotent stem cells and chimeraplasty. This brief review highlights the gene therapy strategies, current developments, challenges and future perspectives for hemoglobinopathies.

  19. Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Chuan-gang Peng

    2015-01-01

    Full Text Available Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

  20. Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recover y

    Institute of Scientific and Technical Information of China (English)

    Chuan-gang Peng; Shu-quan Zhang; Min-fei Wu; Yang Lv; Dan-kai Wu; Qi Yang; Rui Gu

    2015-01-01

    Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantationviathe tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These ifndings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.