Day 2 :
- Track 5: Cellular Therapies
Cell Therapy Catapult, UK
D. Y. Patil University, India
Benedict College, USA
Time : 09:50-10:10
Yavuz Cakir has completed his Ph.D. at the University of Tennessee and postdoctoral studies at University of Alabama at Birmingham. He has more than 10 years experience in preclinical and basic research, academic medicine and clinical and laboratory sciences. He conducted research on the mitochondrial diseases and published several articles. His focus is on the cancer, aging, mitochondrial DNA damage, cardiovascular diseases, atherosclerosis, ethanol metabolism, free radicals and caloric restriction.
There is growing evidence that many forms of diseases including cancer, diabetes, obesity, atherosclerosis, Multiple Sclerosis and Alzheimers disease can be initiated by free radical mediated events or oxidant stress. A cellular source and target of free radical or reactive oxygen species (ROS) production and damage is the mitochondrion.The interaction of mitochondria with ROS modulates cell-signaling pathways and molecular events that control ROS production.Because mitochondria are essential for multiple cell functions, including energy production, redox signaling, cell growth, proliferation, and apoptosis, ROS induce mitochondrial damage and dysfunction in various cells.The effects of ROS on the cells can vary. Under oxidative stress, cycling cells show cell cycle checkpoint responses with a wide array of different mechanisms to block or repair the damage caused by ROS to maintain genomic stability. These mechanisms consist of oxidative response enzymes such as SOD, catalase and glutathione peroxidase (GSH-Px), MPO, iNOS, antioxidants, DNA repair enzymes. However, high levels of unregulated ROS severely impair cellular functions by inducing DNA damage and signaling cascades.Eating disorders and obesity may abnormally increase the amount of ROS and induce disease formation. Caloric restriction on animals and humans reduces the production of ROS and even prolongs the human and animal life. It seems therefore that although a balance between the activation and adaptation of several mechanisms controlled by oxidative signaling occurs, in many chronic diseases these adapted systems are more like lyto respond in an abnormal manner under oxidative conditions.
D. Y. Patil University, India
Time : 10:10-10:20
Shivdas Ganpati Nanaware is a Dean, Faculty of Interdisciplinary studies and Co-ordinator, Stem Cell and Regenerative Medicine Department at Center for Interdisciplinary Research, D.Y.Patil Unviersity, Kolhapur, Maharashtra,India. Prof. Nanaware completed his Ph.D. at the age of 30 years from Shivaji University Kolhapur.After completion of his Doctorate he has served in the same University as a Professor and Head, Department of the Zoology for 35 years. Prof. Nanaware has a unique combination of rich scientific research and administration experience. His research is related to cellular changes in response to water polluting toxicants, pesticides and plant derived bioactive compounds. His research work on crop distructive molluscan pest snails and slugs is well recognized by the researchers working in Malacology.He has developed a Confirmatory Metachromatic Histochemical Technique for the detection of unusual Polysaccharide, Galactogen in animals. He has published more than 60 papers in reputed generals and has guided 20 research scholars for their M.Phil. and Ph.D. degrees. He is a member of editorial boards of many Journals of cell and tissue research. He has attended several national and international conferences in India and abroad. Prof.Nanaware is a life member of many professional societies. He has received several awards and honors in recognition of his meritorious research work. He is a recipient of Best Teacher Award, Govt. of Maharashtra and Shivaji University, Kolhapur. He is also a Gold Medal Awardee of Academy of Environmental Biology. Dr.Nanaware has interest in many branches of Zoology, Toxicology, Neurobiology, Cell biology Stem Cell and Regenerative Medicine and Clinical Application of Cell Therapy.
The wound management forms an important part of the medical and pharmaceutical concern worldwide. Many methods were traditionally used to cure wounds including dressing with natural or synthetic bandages such as cotton, wool, lint and gauzes, and the extracts of plant parts, oils and ghee. The effective wound management depends on understanding a number of different factors such as the type of wound, the healing process , condition of the wound in terms of health and infection ( e.g. diabetic) environment and social setting and the physical and chemical properties of the available dressings. In recent advances it has been proved that the platelets, one of the blood cellular elements, play important role in the wound healing mechanism both in wounds and non-healing diabetic wounds. Platelet cells are practically involved in every event of the wound healing cascade including homeostasis, proliferation, remodeling and cell signaling. Platelet cell growth factors like PGDF, TGF Alfa , TGF Beta and EGF help in chemotaxis, fibroblast proliferation, collagen production and metabolism, epithelial cell proliferation and granulation and tissue formation related functions in wound healing. With the development of platelet cell based procedures at our center such as use of activated platelets, platelet riched plasma (PRP), polymer based scaffolds of Polyvinyl alcohol (PVA) and Polyethylene glycol (PEG) and their combinations have showed dramatic and interesting changes during wound healing. Our efforts in developing the human skin engineering, cellular matrices and cell based therapies are in progress to improve perfect wound healing process. We hope that the potential application of these technologies will be helpful to the people with wounds in general and non-healing diabetic wounds in particular in the near future and will insure rapid and complete healing key strategy for the wound management.
Moritz C. Oberstadt has completed his Ph.D. at the age of 25 years from Ernst Moritz Arndt University Greifswald and works at the Center of Drug Absorption and Transport (C_DAT) in Greifswald, Germany. His research is focusing on Neuro-Oncology and he is the scientific coordinator of a German Neuro-Oncology Young Investigators Meeting.
Glioblastoma multiforme (GBM) is still the most frequent primary brain tumor in adults and is characterized by a highly aggressive phenotype. Despite advances in therapy, glioblastoma remains associated with poor prognosis and an overall survival time of about 1 year. A major underlying factor is resistance to different chemotherapeutics. Several chromosomal, genetic and epigenetic alterations were identified in GBM, but the clinical value of the most glioma-associated molecular aberrations remained unclear. However, a significant prognostic impact could be shown for the O6-methylguanine-DNA-methyltransferase (MGMT). The MGMT functions as a DNA repair enzyme, which repairs alkylating lesions of the DNA by removing mutagenic adducts from the O6 position of guanine, e.g. caused by the chemotherapeutic agent temozolomide. Hence, it confers drug resistance and the therapeutic response to alkylating agents is improved in tumor cells expressing low levels of MGMT. Furthermore, MGMT promoter methylation was demonstrated to result in decreased MGMT expression and correlates with a survival benefit in glioblastoma patients treated with alkylating chemotherapeutics such as temozolomide. Besides methylations histone modifications gain attention in glioma. Histone H3 modifications are involved in tumor cell proliferation and cell cycle progression. Further, histone modifications are connected to metabolic events in gliomas making them a pivotal therapeutic target in the future.
Federal University of Itajuba, Brazil
Title: Selective radiotherapy through liposomes containing 159Gd radioisotope in mice: a pioneer in vivo study
Time : 11:55-12:15
Daniel, bachelor in chemistry, has completed his Ph.D in Pharmacy in 2011 at the age of 28 years at Federal University of Minas Gerais (Brazil) and postdoctoral studies from Stanford University School of Medicine (California). He is the coordinator of Health engineering department of Federal University of Itabuja. He has published more than 20 papers in reputed journals and serving as an editorial board member of repute. Was awarded in 2012, with the prize CAPES Thesis as a best doctoral thesis of Brazil in health area in 2011.
In previous studies, our research group tested in vitro antitumor activity of the isotope 159Gd-DTPA-BMA (Omniscan® - GE Healthcare) encapsulated in stealth pH-sensitive liposomes against RT2 tumoral cells (murine glioma). The results revealed that the presentation of a radioisotope to tumor cells, coupled with the effect of ionizing radiation, potentiated the cytotoxic effect by a factor of 1170. Additionally, we investigated the biodistribution profile of liposomes encapsulating the complex radioactive 159Gd-DTPA-BMA in mice containing the previously inoculated and developed solid Ehrlich tumor. The results revealed a significant accumulation of the formulations in tumor tissue, showing that the formulation has potential for use in therapeutic procedures for cancer treatment. In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the 159Gd-DTPA-BMA radioisotope. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower tumor volume gain without significant hematological or biochemical changes.
Cell Therapy Catapult, UK
Time : 13:35-13:55
Johan was appointed Chief Scientific Officer of the Cell Therapy Catapult in May 2013. As Chief Scientific Officer, he is responsible for external scientific relations, assessment of candidate projects and technical oversight of preclinical programs. He has extensive experience of the life sciences industry, having worked in cell and tissue companies in Europe and the U.S. for over 15 years. Johan has been involved in numerous transactions and collaborations, establishment of scientific facilities, and the management of scientific programs in industry and academia. He has published more than 60 full length scientific papers.
Cell therapy represents the most recent phase of the biotechnology revolution in medicine. As with most remedies, cell therapies are based on ground-breaking scientific discoveries. Many of the achievements in the cell therapeutic space are quite recent.Importantly, progression of cell therapies brings a whole raft of scientific, manufacturing, regulatory and commercialisation issues to be solved. Very few organisations that work in the space currently have all these capabilities in-house. Thus, it is clear that collaborations between academic institutions, pharmaceutical enterprises, biotechnology companies and other stakeholders are important to accelerate the therapeutic developments.In the UK, the major barriers for the growth of a cell therapy industry have been identified as being regulatory, business, manufacturing and supply chain related. To overcome these hurdles the Technology Strategy Board, a governmental agency, founded the Cell Therapy Catapult to provide a critical mass of expertise to bridge the translational gap from bench to bedside and address the issues described above.New ways of effective partnering for innovation and investment in innovation will be described as will strategies to overcome manufacturing and regulatory challenges that exist today.
Al-Azhar University, Egypt
Time : 13:55-14:15
Abdelhakim Mohamed Safwat , Medicine doctor, now is Assistant lecturer of ophthalmology department, Al-Azhar Univ. Member in Egyptian society of ophthalmology (EOS), Egyptian vetrioretinal society. He got B Sc in medicine 2003, master in ophthalmology (treatment modalities in age related macular degeneration), and diploma in uses of laser in medicine. His working experiences: internship in Al-Azhar Univ. hospitals for one year, resident in ophthalmology department for 3 years, fellow in international eye hospital for 3 years and assistant lecturer up till now. His studies focus on regenerative medicine in ophthalmology mainly age related macular degeneration and retinitis pigmentosa. Scientic activities: speaker in international neuropsychatric conference of Alexandria University, annual conference of clinical pathology department of cairo University, Egyptian vitreoretinal society meeting 2014, international conference of stem cell and nanotechnology of Ainshams University and stem cell scientific meeting in national institute of research.
Retinitis pigmentosa is a common label for a heterogeneous group of heritable retinal degenerative diseases that result in progressive visual loss secondary to photoreceptor cell death. Of the 2 photoreceptor cell types in retina (Rods and cones), these diseases primarily affect rods; the cones die an “innocent bystander” death. This is reflected in the natural clinical course of retinitis pigmentosa, which usually begins with loss of rod-mediated night vision and advances over the years with progressive loss of the peripheral visual field and, ultimately, the loss of central, cone-mediated vision. There is concomitant attenuation of the retinal vasculature. It is thought that vascular loss follows decreased metabolic demand by the photoreceptors. Currently no definitive treatment for retinitis pigmentosa exists, although nutritional approaches may slow some forms of this disease. Mesenchymal stem cells (MSCs) are progenitors of all connective tissue cells. In adults of multiple vertebrate species, MSCs have been isolated from BM and other tissues, expanded in culture and differentiated into several tissue-forming cells. A number of studies have shown that bone-marrow-derived MSCs can differentiate into cells expressing photoreceptor proteins. In this study we use adult bone marrow mesenchymal stem cell to restore vision in RP patients, patients divided in two groups one had intravitreal injection and the other had injection after vitrectomy. Results are compared according to visual outcome , investigations and complications . Finally the use of mesenchymal stem cell is useful in cases of retinitis pigmentosa and other retinal dystrophies.
Sultan Qaboos University, Oman
Title: Mesenchymal stem cells to repair vascular damage after chemotherapy: Past, present and future
Time : 14:15-14:35
Sulaiman Al-Hashmi received his Ph.D. degree from KarolinskaInstitutet in 2011. He is managing the National Tissue Typing Laboratory in Sultanate of Oman. Dr. Al-Hashmi current work is focused on the use of MSC on tissue repair and regenerative medicine. He has published several papers in peer reviewed journals.
The use of hematopoietic stem cell transplantation (HSCT) is continuously expanding to cover a broader range of diseases. Because HSCT implicates the immune system, the new cells from the donor cannot be engrafted without compromising the recipient immune system. Currently, approximately 50 % of patients undergoing HSCT are conditioned with chemotherapy. Although the chemotherapeutic regimens have improved the outcomes of transplanted or cancer patients they have been associated with severe side effects that can considerably compromise the quality of patients’ life. Recent studies have shown that even short-term chemotherapy can cause vascular injury that leads to potential adverse cardiac effects, including heart failure and hypertension. Mesenchymal stem cells (MSC) therapy could be a promising procedure to reduce vascular damage and increase tissue repair as these cells are endowed with a potent tissue regeneration capacity along with immunosuppressive properties. MSC therapy can decrease cardiotoxicity and improve vascular repair following chemotherapy regimens. Additionally, MSC infusion can influence the function of the endothelial cells and the level of the growth factors, inflammatory cytokines and immune cells. Collectively, understanding of MSC as a pharmacological tool to repair vascular damage and other organ dysfunction following chemotherapy in HSCT or cancer patients is of paramount importance to develop effective protocols.
Navy General Hospital, China
Title: Intracoronary infusion of a very primitive population of mesenchymal stem cells in acute myocardial infarction: A randomized, double-blind, placebo controlled, multicenter trial
Time : 14:35-14:55
Context The use of adult stem cells is limited by the quality and quantity of host stem cells. Wharton’s jelly–derived mesenchymal stem cells (WJMSCs), a very primitive population, may integrate into ischemic cardiac tissues and significantly improve heart function in preclinical models. Objective To assess the safety and efficacy of intracoronary infusions of WJMSCs in patients with ST-elevation acute myocardial infarction (AMI) in a randomized, double-blind, placebo-controlled study. Design, Setting, and Patients Subjects with AMI (n=160) were screened and 116 eligible patients were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarcted artery 5-7 days after successful reperfusion therapy at 11 hospitals in China. Main Outcome Measures For the primary endpoint of safety: the incidence of adverse events (AEs) within 12 months was monitored and quantified. For the endpoint of efficacy: the absolute change in global left ventricular ejection fraction (LVEF) from baseline to 12 months, myocardial viability and perfusion in the infarcted region from baseline to 4 months were measured using two-dimensional echocardiography, F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), respectively. Results During12 months follow-up, adverse event rates and laboratory tests including tumor, immune, renal, hepatic, and hematologic indexes were not different for patients receiving WJMSCs or placebo. The absolute improvements in the myocardial viability and perfusion within the infarcted territory at the 4-month follow-up in patients receiving WJMSCs (6.9±0.6%, 95% CI 5.7-8.2 and 7.1± 0.8%, 5.4-8.8, respectively) were significantly greater than those in patients receiving placebo (3.3±0.7%,1.8-4.7, P<0.0001, and 3.9±0.6%, 2.8-5.0, P=0.002, respectively). The absolute increase in LVEF at 12 months in the WJMSC group was significantly greater than that in the placebo group ( 6.7±0.8%, 5.1-8.3 vs. 3.5±0.8%,1.9-5.0, P=0.004 ) . The LV end-systolic volumes at 12 months was significantly decreased from those at baseline in the WJMSC group (P=0.0002), whereas no significant changes were observed in the placebo group. Conclusion Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window and at an effective dose. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel allogeneic source for cardiac stem cell-based therapy. Trial Registration: NCT01291329.
- Track 6: Advanced Gene Therapeutics
Life Technologies, USA
Swedish University of Agricultural Sciences, Sweden
Swedish University of Agricultural Sciences, Sweden
Time : 15:40-16:00
Wilhelm Engstrom received his Ph.D. and M.D. from Karolinska Indstitutet. He worked as a postdoctoral fellow at University of Oxford for eight years before he was appointed professor of general pathology at the Faculty of Veterinary Medicine, Uppsala Sweden. He is the current president of the European Cell Proliferation Society, a fellow of the Royal Uppsala Society of Sciences and a fellow of the Royal College of Pathologists (U.K.).
The Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals. Igf2 is a growth factor expressed in most normal tissues solely from the paternal allele. In contrast, the H19 gene is transcribed (but not translated to a protein) from the maternal allele. The Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both fetal and placental growth and also nutrient placental transfer from mother to offspring. The epigenetic regulation of the Igf2/H19 gene-cluster leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and the three-dimensional partitioning of DNA in the nucleus. The enhancer competition model, the boundary model, and the chromatin-loop model are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways will be discussed that can account for the allelic methylation differences, as there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of the differential methylation-pattern. These models provide novel concepts for the development of new therapeutic traits in human cancer.
National Centre for Biological Sciences (NCBS), India
Title: Tryptophan hydroxylase gene involvement in the serotonergic abnormality of autism spectrum disorders: A genetic and genotype –phenotype correlation study
Time : 16:00-16:20
A.S. Singh has is presently working as postdoctoral fellow in Dr. Axel Brockmann’s Lab at NCBS. He completed his Ph. D research in May 2013 in the University of Calcutta under the supervision of Dr. Usha Rajamma. His main research interest is to understand the mechanism of how genes regulate behaviors through certain neural circuitry systems.
One of the most consistent finding in ASD research is the presence of high serotonin level in the blood platelets of 30% ASD subpopulations. Abnormal serotonin synthesis capacity has also been implicated in the brain of ASD individuals. Even though serotonergic pathway in brain and the periphery is differentially regulated, during early stage of life when the blood brain barrier is not fully formed, the only rate limiting enzyme available for serotonin biosynthesis is the peripherally expressed TPH1 which is the isoform of brain specific TPH2. On the light of these evidences the present study is a thorough investigation of TPH1 gene to find the risk locus for serotonergic abnormality in ASD. From the family based approaches with individual markers, we found that A allele of rs10488682 is significantly overtransmitted from parent to female probands. Two-locus haplotype analyses showed significant overtransmission with various combinations of different SNPs that include rs623580, rs1800532, rs684302, rs1799913, rs211106 and rs10488682. Similar observation was also found with three locus haplotype models. Functional prediction analysis illustrated polymorphisms of these markers have very low to moderate effect on the gene regulation.
Investigation with platelet serotonin assay showed that 33% of ASD individuals are hyperserotoninemic in our study population in India and is very close to the earlier reports of 30% (approx). Furthermore, quantitative trait association analyses with specific alleles, genotypes and haplotypes also demonstrated involvement of rs684302, rs211106, rs1800532 and rs1799913 of TPH1 in the increased platelet serotonin level of ASD. Thus our various approaches with genetic association studies and genotype-phenotype correlation analyses suggest involvement of TPH1 in the pathophysiology of ASD through the regulation of serotonin level. Since we do not have the functional experimental data, our findings provide the preliminary evidences. However, these data highlight the need of extensive research both in genetic and functional level for clear understating of TPH1 involvement in the etiology of ASD.
Sookmyung Womens University, Republic of Korea
Title: Natural compound derived Z-ajoene decreases NOTCH signaling in U87-derived Glioblastoma cancer stem cell
Time : 16:20-16:40
Yuchae Jung has completed her Ph.D at the age of 30 years from Catholic University majoring computational Biology. She did her postdoctoral studies from Brigham and Womens Hospital working on the relationship between Glioblastoma and cooperative miRNAs. She continued to work on the relationship between GBM cancer stem cells with miRNA profiles supported by Korean National Research Foundation grant. She has published more than 12 papers in reputed journals.
Glioblastoma multiform (GBM) is the most common brain tumor and the GBM patients have a poor prognosis with median survival of one year. Recent evidence suggests that the presence of cancer stem cell (CSC) in GBM and it is expected that rare CSC subpopulation is resistant to chemotherapy and may lead to recurrence and metastasis. CSCs can self-renew such as normal stem cell and have highly tumorigenic property. In this study, we screened natural compounds including Z-ajoene with anti-CSC effect and observed that Z-ajoene has anti-CSC effect. Although Z-ajoene is known to have anti-tumor effects, but its mechanism is not clearly understood yet. In this study, we examined putative mechanism through focusing on self-renewal pathways associated with survival and maintenance of CSCs. Z-ajoene decreased the transcript level of Notch, Wnt, TGFβ, and PI3K/AKT pathways which is related with stemness and maintenance of CSCs. While Z-ajoene showed elevated activity of ERK and P38 pathway which is related with cellular stress. These results suggest that Z-ajoene can be an anti-CSC drugs which has less side effects and cytotoxicity.
Keywords: GBM; cancer stem cell; Notch pathway; Wnt pathway; TGFβ pathway; Erk pathway; PI3K/AKT pathway
Chonnam National University Medical School, Republic of Korea
Title: Bacteria-mediated expression of cargo drugs and reporter gene for cancer-specific theranostics
Time : 16:40-17:00
Jung-Joon Min has completed his M.D and Ph.D. from Chonnam National University and postdoctoral studies from UCLA and Stanford University School of Medicine. He is the professor and director of Nuclear Medicine at Chonnam National University Medical School and Hospital. He has published up to 90 papers in reputed journals and serving as an editorial board member of repute.
Use of microbial system has attributed to the recent advances in targeted molecular therapy application especially for its tumor-specific accumulation and proliferation. In an attempt to investigate tumor-specific targeting, we used an in vivo optical or PET imaging system to monitor the spatial and temporal migration of E. coli or attenuated Salmonella typhimurium following injection into mice models carrying a variety of tumors. The phenomenon of selective targeting and proliferation of bacteria was observed in a diverse range of tumors, both primary tumors and metastases. Bacterial therapy possesses many unique applications for treating cancer that are unachievable with conventional treatment. Bacteria can specifically target tumors, actively proliferate there, are easily detected and can controllably induce cytotoxicity. When using tissue specific or inducible system, bacteria could be engineered to express target genes specifically in the tumor area, rather than other organs, leading to maintenance of therapeutic efficacy and reduction of toxicity. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth. The combination with engineered bacteria (BT) and radiotherapy (RT) had synergistic effect to completely remove the subcutaneously grafted tumor. In this research, we propose that synthetic biology techniques can be used to solve many key challenges that are associated with bacterial therapies, such as toxicity, stability and efficiency, and can be used to tune their beneficial features, allowing the engineering of ‘perfect’ bacteria for cancer treatment.