Title: The Lack of Fam83h Mediated Reduction of Wnt/?-Catenin Signaling Pathway and Expression Levels of Dental Mineralization Genes

Abstract:

Background: FAM83H has been identified as an essential gene for dental enamel formation and may be related to Wnt/β-catenin. Methods: levels of Fam20a, Dspp, Dmp1, Enam, Ambn, Sppl2a, Mmp20, Fgf10, and the mediators of Wnt/βcatenin pathway were measured in the dental root of both Fam83h-KnockOut and wild-type mice by using QPCR at 5,11 and 18 days after birth. The expression of Fgf10 and the mediators of Wnt/β-catenin were also evaluated in the skin of KnockOut and wild-type mice by using Q-PCR and also, The histology of hair follicles was compared. the Fam83h-KnockOut mice recruited in this study were confirmed by Sanger sequencing and western blot analysis. Results: Our results showed that Ambn, Mmp20, Dspp, and Fgf10 significantly reduced in Fam83h-KnockOut mice in the dental root, associated with marked reduction of CK1a, CK1e, and β-catenin expression in Fam83hKnockOut mice in the dental root. The Fgf10, CK1a, CK1e, and β-catenin were significantly decreased in the skin of Fam83h-KnockOut mice. In the absence of Fam83h, the accumulation of unemployed CK1a is expected to elevate the β-catenin destruction complex. The reduction of CK1e may also decrease the signaling of Dvl-1, leading to the suppression of the Wnt/β-catenin pathway. Simultaneous reduction of both mineralization genes and the Wnt/β-catenin pathway due to the absence of Fam83h has the potential to be related to the deficiency of dental formation and mineralization. Further, concurrent reduction of Fgf10 gene expression and the Wnt/β-catenin pathway may also affect the maturation of hair follicles as confirmed by histological examination. Conclusion: it seems that in the lack of Fam83h, dental mineralization is induced by simultaneous decrease of Wnt / β-catenin mediators and the mineralization-related genes, suggesting to act in a cumulative effect manner and probably behave as a multi-factorial trait.

Biography:

Sherko Nasseri completed Ph.D. in molecular medicine. Assistant Professor, from Kurdistan University of Medical Sciences, Iran. During my Ph.D. Thesis, I worked on the generation of Fam83h Knockout Mice by using the CRISPR/Cas9 method. The absence of Fam83h these mice has the scruffy cover, dry eye phenotypes, and also these mice were smaller than the same age normal mice. In continuation of this project, we found that the WNT/B-Catenin pathway decreased. The Fam83h gene has a high expression level in the gastrointestinal tract. Given all that has been said, it brings me a critical question that how does the fam83h gene play role in the gastrointestinal tract?

Title: Controlled Drug Delivery Based On Biocompatible Polymeric System

Abstract:

Several metallic macrobiotic actuators have been developed in the recent past, that have enabled the target-oriented advanced drug delivery system (DDS) for specific applications like cancer and gastrointestinal medication. The method involves the use of microbots or actuators that contain drugs and enable the controlled drug delivery at the site based on temperature, pH, light, electric, and magnetic field sensitivity. Other techniques were based on a single or combination of the above-mentioned criteria. The materials used for actuators or microbots either lack in delivering the required amount of drug or it does not remain inside the body for long. To overcome these problems, we are interested in providing better solutions to them by using suitable gripping techniques and polymeric systems for long-term exposure, with the controlled release of sufficient drugs at the site. The application of polymers showed that these responsive materials can overcome addressing limitations associated with metals used in a wide array of medical devices in the novel drug delivery system. Amphiphilic polymers have played a key role in the development of advanced drug delivery technologies by controlling the solubility, permeability, and stability of active ingredients. Amphiphilic polymers possess the ability to encapsulate hydrophobic drug molecules inside their hydrophobic core, hence increasing the aqueous solubility of the drug. The problem of controlled drug delivery of polymeric systems could be achieved by embedding nanofillers to it. The polymeric nanocomposites could form a tortuous path for the diffusion of drugs through it due to the impermeable particles in it, leading to enhancement of the controlled release rate. Various tortuous path models have already been developed that specifies the diffusion rate of solutes through such composites. The oral route is considered the most preferable route for drugs administration. While encapsulation could be done for the drug transport for the oral route, the solution to its retention lies in the spiked surface structure similar to the orchid that would be responsible for its attachment to the intestinal surface. So far literature reviews of such systems with techniques, process parameters, limitations, and the future scenario were analyzed and a plan for a suitable drug delivery system is made to overcome such limitations and provide better solutions to them. The challenges involve DDS synthesis, encapsulation, transport to specific sites, gripping power, polymer-drug interaction, and long-term exposure to cells. The overall work is to develop encapsulated, pH active, thermally assisted polymeric DDS that could be used orally, having biocompatibility and better attachment to cancer cells.

Biography:

Sana Zahra has done MSc in Applied Biochemistry in 2010 (Gold Medalist). With a better record in earlier studies and interest in research, she is trying to get back into research even after a long-term gap in her studies.

Title: Regeneration in Prosthodontics – A Challenge?

Abstract:

The ultimate goal of prosthodontic treatments should be to regenerate the missing teeth together with the periodontal structures. Many prosthodontists have thought “I could have achieved a better treatment outcome if regenerative therapies were more readily available.” To date, prosthodontists have been managing missing teeth/alveolar bone by “replacement prosthodontics” using artificial materials such as dentures and dental implants. The recent development of stem cell-based regenerative medicine has introduced the concept of “regenerative prosthodontics” to our field, particularly in cases of missing teeth with severe alveolar bone resorption. This is mainly possible with the help of stem cells. Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide to produce extra stem cells. They are originated in multicellular organisms. They may be embryonic or adult stem cells. The stem cells of the dental pulp are the mesenchymal stem cells (MSC). They are the most commonly used stem cells. However, bone marrow-derived mesenchymal stem cells are a commonly used cell type for utilization in cell-based regenerative approaches in prosthodontics. They help to build the bone structures of the craniofacial region, particularly the maxilla and mandible. Stem cell therapy is one of the most recent advances in the dental field. Its use establishes a 100% success rate. Thus, knowing its value is of prime importance. The presentation includes various challenges in relation to regenerative therapies being used as well as recent trends n regenerative prosthodontics.

Biography:

Arpit Sikri [BDS (Gold Medallist), MDS (Prosthodontics), PGDHM, DWCOI] is currently working as an Associate Professor & Post Graduate Teacher in the Department of Prosthodontics, Bhojia Dental College & Hospital, Baddi, Himachal Pradesh, India. He had earlier worked as Senior Resident in the most prestigious dental institute of the country i.e. Maulana Azad Institute of Dental Sciences, New Delhi, India. He had also worked as Senior Lecturer in Santosh Dental College, Santosh Deemed to be University, Ghaziabad (Delhi NCR) & Senior Lecturer in Sudha Rustagi College of Dental Sciences & Research, Faridabad, Haryana, India. He is the youngest dental surgeon of India to have completed his Post Graduate Diploma in Hospital Management from the National Institute of Health and Family Welfare (NIHFW, New Delhi), and that too with distinction. He has also been conferred with Diplomate Fellowship in the field of implantology by World Congress for Oral Implantology (WCOI), Tokyo, Japan. Throughout his academic career, he had been awarded gold medals being the Topper of the University, back to back. He has authored a book on “Oral Pathology” under Scientific Medtech publishers. He has to his credit around 28 books under Lambert Academic Publishing (LAP) and more than 100 national as well as international publications in various reputed journals. He is the Editor of Web med Central, Associate Editor of Current Dental Research Journal, and Assistant Editor of Asia Pacific Dental Journal & I-Dentistry journal. He is on the panel of various national and international journals as an editorial board member. Apart from this, he is also an active reviewer for various journals. He is actively associated with various associations namely IPS, IDA, IDRR, AHA, etc.

Title: Cancer Immunotherapy: T cell against cancer

Abstract:

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy, and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.

Biography:

Daniela Capdepon Graduate from the University of F. Medical Barceló in 2001 with honors and the highest academic average. She is a Residency in Internal Medicine at the  Campana, Zarate Municipal hospitals, Fundaleu, and COBA oriented Graduate Clinical Oncology 2002 – 2004. Daniela Capdepon has been working as a Medical physician for the last 20 years. Daniela Capdepon has been working as a Consultant Medical Oncologist for the last 15 years. Daniela Capdepon is very interested in the new advances in Oncology and everything related to my specialty and immunotherapy. As well as teaching. Daniela Capdepon would like to work in a University Hospital, where you can work and represent in the Congresses and Committees, the different jobs that are carried out and developed in the hospital. I am really interested in continuing to develop my career and progress in my profession.

Title: Establishing an efficient contamination control in Pharmaceutical

Abstract:

Sterility is a key quality attribute for a class of medicines required to be sterile. The consequences of non-sterility are direct patient harm. The degree of harm is dependent upon the route of administration and the types and numbers of microorganisms, as well as the health and immune state of the patient. The likely outcomes of the administration of a non-sterile product are disability or death. For this reason, contamination control is an important part of both sterile and non-sterile pharmaceutical manufacturing, regulators, as signaled by the revised EU GMP Annex 1 and from FDA inspections are increasingly expected the contamination control to be devised and presented as a formal program. This means a detailed, facility-specific contamination control strategy. Therefore, the objective is to develop a robust program that reviews, assesses, and reaffirms strategies for the prevention & remediation of contamination risks. This paper sets out the key elements of the strategy. To be effective, this needs to be an approach that can assess seemingly isolated contamination events holistically and which is capable of putting appropriate corrective and preventive actions (CAPAs) in place. This approach signals a new paradigm in terms of contamination control, shifting the risk review process to one that assesses the impact of a contamination event in a far wider context.

Biography:

Zeinab El-Zein has completed a master's degree in biochemistry from the Lebanese University faculty of sciences. Being a quality-oriented & talented Microbiology Supervisor with up to 8 years of experience in this field,  her expertise is particularly in the areas of quality management, auditing, compliance, quality improvement, and change processes. Throughout her career, she has held various positions. From this frame of reference, Zeinab El-Zein has a quick insight and overview in organizations related to processes and their link to quality.

Title: Stem Cells Applications in Regenerative Medicine

Abstract:

Regenerative medicine is an important vanguard of the biomedical industries, and all countries urge to put in lots of resources in research and development. Taiwan Mitochondrion Applied Technology Co., Ltd (TaiMito) is an emerging leader in the worldwide development of regenerative medicine on mitochondrial technology. TaiMito focused on mitochondrial R&D and application technology platforms since 2014 and is the first company that develops mitochondria as biologics through Mitochondrial Reconstruction Technology (MRT).​ The population of aging around the world is increasing dramatically. Mitochondrial dysfunction is closely associated with the development of aging and degenerative diseases (such as Parkinson's disease and Alzheimer's disease... etc.). Because impaired mitochondria will be insufficient to energy supply and trigger reactive oxygen species induction, and even result in cells to enter apoptosis or autophagy, which will lead to disease. Currently, a number of product pipelines have been developing, including MitoCell (stem cells), MitoBio (Mitochondria), MAKcell (immune cells), MitoScan (functional mitochondria assay), and Stemoto (stem cell culturing medium). MitoCell, MitoBio, MAKCell are preparing to enter the next stage of a clinical study, and other products or testing services are marketed in the fields of preventive healthcare supplements, aesthetic medicine, stem cell culture medium, health examination, and mitochondrial metabolomics. These products or services have been demonstrated to be safe, and effective in preliminary studies. Our major priority is to launch the MitoCell to targeted markets. MitoCell is an autologous stem cell product that cultures with the company's unique patented medium. The mechanism of action (MOA) of MitoCell is to improve the brain microenvironment in neurodegenerative disease. MitoCell which like mesenchymal stem cells can modulate the immune response. Moreover, MitoCell can secrete more abundant regulators, such as BDNF/GDNF, SDF-1, IL-1ra, BECN-1...etc., to help dopamine neurons (DA) repair, restore, and regenerate, and even eliminate toxic α-Synuclein through up-regulating autophagy. Therefore, MitoCell can reconstruct the brain environment to a better site for DA residents and showed more efficacy than other stem cells. In our study, BDNF is one of the major potency markers of MitoCell. We have successfully initiated MitoCell to phase I open-label dose-escalation study to evaluate the safety, tolerability, and efficacy of autologous MitoCell intracranial transplantation in subjects with idiopathic Parkinson’s disease which rating from stage 3 ~ 4 of modified Hoehn & Yahr staging. Two dose levels will be tested. This clinical trial plans to enroll approximately 4 subjects to obtain 3 evaluable subjects successfully receiving 3×10⁷ cells/hemisphere (total 6×10⁷ cells, Cohort 1) and approximately 8 subjects to obtain 6 evaluable subjects for 1×10⁸ cells/hemisphere (total 2×10⁸ cells, Cohort 2). The primary objective of this study is to assess the safety profile of autologous MitoCell administered to PD patients, and the secondary objective is to explore the efficacy and safety of MitoCell given as the recommended dose by stereotactic intrastriatal implantation.

It was clear that none of the current treatments can rescue the degeneration of the brain function in PD patients and eventually the patients will inevitably become disabled. However, MitoCell therapy may provide a potential solution. The following potential benefits are expected within one year:

• - Improvement in motor function: shall be reflected on reduction of UPDRS motor score by 20~40%.
• - Reduction of PD medication: shall be reflected on LEDD and without the side effect of graft-induced dyskinesia.
• - Better quality of life: shall be reflected on the PDQ-39 scale.

It is also possible that subjects may benefit more than one year if MitoCell manages to survive longer or change the microenvironment/inflammation status of the lesion site for the long term to prevent progression of neuron degeneration.

Biography:

Chi Tang Tu graduated from National Taiwan University with a major in Molecular and Cellular Biology. During his postdoctoral research in the Surgery Department of National Taiwan University Hospital, he is specialized in the studies of adipose-derived stem cells and amnion stem cells for the disease of liver fibrosis/cirrhosis. Chi Tang Tu has his expertise in stem cells, mitochondria, CIK, and NK cells CMC-related activities, including development and manufacturing of drug substance, drug product, new chemically defined stem cell culturing, and conditioned medium, to support preclinical development through supplies for clinical phases. Many years experience of in managing and establishing GTP and PIC/S GMP facilities compliance with GLP, GTP, and PIC/S GMP. Furthermore, he led an intensive R&D team in the development of the isolation, scale-up, and cryopreservation process of mitochondria products (biologics) for augmenting therapy of neurodegenerative diseases and age-related infertility. His RD team built an innovative mitochondria functional analysis platform to assess cell drugs quality and to apply in blood BHI (bioenergetic health index) assay for preventive medicine. At the company, Chi Tang Tu also supports business and strategy development, patent deployment, engagement, and negotiation with venture capital or clients, and is in charge of translating our RD works from bench to bedside to business.

Title: Stem cell therapy in radiotherapy from bench to Clinical Trial Evaluating the Efficacy of Mesenchymal Stromal Cell Injections for the Treatment of Chronic Pelvic Complications Induced by Radiation Therapy

Abstract:

The late adverse effects of pelvic radiotherapy concern 5 to 10% of patients, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Our group has demonstrated in preclinical animal models that systemic mesenchymal stromal stem cells (MSCs) injection is a promising approach for the medical management of gastrointestinal disorder after irradiation. In a phase 1 clinical trial, we have shown that the clinical status of four first patients suffering from severe pelvic side effects (Epinal accident) was improved following MSC injection (figure). Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. The frequency of painful diarrhea diminished from 6/d to 3/d after the first and 2/d after the 2nd MSC injection in one patient. A beginning fistulization process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response. MSC therapy was effective on pain, diarrhea, hemorrhage, inflammation, fibrosis and limited fistulization. No toxicity was observed. We are now starting a clinical research protocol for patients with post-radiation abdominal and pelvic complications who have not seen their symptoms improve after conventional treatments (NCT02814864, Trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdomino-pelvic complications refractory to standard therapy (PRISME). It involves the participation of 6 radiotherapy services for the recruitment of 12 patients. They will all be treated and followed up in the hematology department of Saint Antoine Hospital. The cells will be prepared in two production centers (EFS Mondor and CTSA). Treatment is a suspension of allogeneic MSCs. Eligible patients must have a grade greater than 2 for rectoragy or hematuria at inclusion and absence of active cancer. Each patient receives 3 injections of MSCs at 7-day intervals. Patients will be followed up over a 12-month period. The main objective is a decrease of one grade on the LENT SOMA scale for rectorrhagia or hematuria. The secondary objective is to reduce the frequency of diarrhea; analgesic consumption, pain and improved quality of life.

Biography:

For 25 years, he has been developing gene and cell therapy using non-human primates, immune-tolerant mice, and rats to protect against the side effects of radiation. He collaborates with clinicians to develop strategies for the treatment of patients after radiotherapy overexposures. He has participated in the first establishment of proof of concept of the therapeutic efficacy of mesenchymal stem cells (MSCs) for the treatment of hematopoietic deficit, radiodermatitis, and overdosages of radiotherapy. He has contributed to the first reported correction of deficient hematopoiesis in patients (graft failure and aplastic anemia) thanks to intravenous injection of MSCs restoring the bone marrow microenvironment, mandatory to sustain hematopoiesis after total body irradiation. He is the scientific investigator of Clinical phase II trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdominopelvic complications refractory to standard therapy

Title: Use of Cell Therapy in solid organ transplantation:

Abstract:

The use of adjusted immunosuppressants has significantly improved graft and patient survival in the early phase after transplantation, but long-term results are often inadequate due to the development of chronic transplant rejection. In addition, long-term immunosuppression has serious side effects that can seriously affect a patient`s survival and quality of life. Achieving tolerance in the long term without the use of immunosuppressants is the ultimate goal of most of the research in the field of solid organ transplantation. Several strategies, including per graft-versus administration of non-hematopoietic immunomodulatory cells, can safely and effectively induce resistance in preclinical models of solid organ transplantation. In my next series of posts, I will be focusing on various evidence of the use of Mesenchymal stem cells in inducing long-term graft tolerance.

Biography:

Renna Rathod Passionate Cell biology scientist with 13 years of experience in academia and industry in national and international settings. she has expertise in culturing and differentiation of human and mouse pluripotent stem cells into different cell types for disease modeling and regenerative purpose, Immuno-oncology (CAR-T), and Viral vector. With her Ph.D. from the University of Wuerzburg and other international collaborations, she has demonstrated the capacity to lead a team, work in a team environment as well as independently and bring several collaborations. 

Title: Identification of key microRNAs in diabetes mellitus erectile dysfunction rats with stem cell therapy by bioinformatic analysis of deep sequencing data

Abstract:

Diabetes mellitus erectile dysfunction (DMED) is a common resulting complication of diabetes. Studies have shown mesenchymal stem cell (MSC)-based therapy was beneficial in alleviating erectile function of DMED rats. While the pathogenesis of DMED and the mechanism MSCs actions are unclear. We constructed a rat model of DMED with or without intracavernous injection of MSCs, and performed microRNA (miRNA) sequencing of corpora cavernosa tissues. We identified three overlapping differentially expressed miRNAs (rno-miR-1298, rno-miR-122-5p, and rno-miR-6321) of the normal control group, DMED group, and DMED+MSCs group. We predicted 285 target genes of three miRNAs through RNAhybrid and miRanda database and constructed a miRNA-target gene network through Cytoscape. Next, we constructed protein-protein interaction networks through STRING database and identified the top 10 hub genes with highest connectivity scores. Five GO terms including cellular response to growth factor stimulus (GO:0071363), ossification (GO:0001503), response to steroid hormone (GO:0048545), angiogenesis (GO:0001525), positive regulation of apoptotic process (GO:0043065), and one Reactome pathway (Innate Immune System) were significantly enriched by 10 hub genes using the Metascape database. We selected the GSE2457 dataset to validate the expression of hub genes and found only the expression of B4galt1 was statistically different (P<0.001). B4galt1 was highly expressed in penile tissues of diabetic rats and would be negatively regulated by rno-miR-1298. Three key miRNAs were identified in DMED rats with stem cell therapy and the miR-1298/B4GalT1 axis might exert function in stem cell therapy for ED.

Biography:

Xiaoqiang Liu is a surgeon by profession and works in Tianjin Medical University General Hospital. He holds a doctoral degree and studied in Tokyo University of Japan for one year. He is mainly engaged in clinical work and basic research of urological oncology and andrology. He has made great contributions to the use of stem cells for the treatment of erectile dysfunction.

Title: Effects of Music Therapy after Autologous Stem Cell Transplantation

Abstract:

The notion that music can influence your thoughts, feelings, and behaviors probably do not come as much of a surprise. If you've ever felt pumped up while listening to your favorite fast-paced rock anthem or been moved to tears by a tender live performance, then you easily understand the power of music to impact moods and even inspire action. Music therapy may be a viable nonpharmacological method of pain management for patients undergoing ASCT. In fact, post-transplantation of stem cell transplantation involves pain and nausea, and its treatment can be physically and psychologically challenged, with many side effects that can be painful, uncomfortable, and sometimes difficult, which takes us to the use of challenging alternative methods to see if there would be helpful positive effects on the treatment.

Biography:

Negin Samadi Kharajouei born in Tabriz , Iran. She is a 2nd-year Bsc student in Cellular and Molecular Biology at the Islamic Azad University of Tabriz Branch in Iran. Her first article titled "Effects of Music Therapy after Autologous Stem Cells" has been published at eight international conferences held in Iran, also under review at the Sydney Conference. She has worked on her Ph.D. thesis under the associate professor Dr. Nasirzadeh on Kidney issues.  This is her great honor to attend the Stem Cells Conference in Miami, USA as a speaker.