Day 1 :
Keynote Forum
Maxim Yu. Rykov
Tver State Medical University, Russia
Keynote: Cell technologies in the treatment of patients with postcovid syndrome
Time : 09:00 AM - 09:30 AM
Biography:
Maxim Yurievich Rykov, born May 22, 1980, was born in Moscow. Graduated from the medical faculty of the Sechenov University. In 2010 he graduated from the residency at the Department of Oncology, in 2013 he graduated from the postgraduate course. 2014 to 2015 From 2015 to 2016, he served as a researcher at the Department of Tumors of the Musculoskeletal System of the Research Institute of Pediatric Oncology and Hematology. - Researcher of the Department of Head and Neck Tumors, from 2015 to 2016. - Senior Researcher of the Social Pediatrics Laboratory of the Scientific Center for Children's Health, from 2017 to 2018. - Senior Researcher of the Department of Head and Neck Tumors N, from 2016 to 2019. - Associate Professor of the Department of Oncology, Sechenov University, from 2018 to 2019. - Deputy Director for Prospective Development of the Research Institute of Pediatric Oncology and Hematology, from 2019 to 2021. - Associate Professor of the Department of Oncology, Sechenov University.
Abstract:
The inclusion of stem cells (SC) in rehabilitation programs for patients with various injuries and diseases of the central nervous system is a new, promising direction of research. Possible mechanisms of therapy for spinal cord injury based on the use of adult-type stem cells from the bone marrow, including CD34 +, include many aspects. On the background of SC transplantation, damaged nerve cells and surrounding tissues, including neurons and glial cells, can be restored, which helps to ensure the integrity of the nerve conduction pathway and, thus, restore nerve function. SA therapy can suppress genes involved in inflammation and apoptosis, as well as activate genes with neuroprotective action, thereby protecting spinal neurons from secondary damage. The introduction of autoCD34 + SC will be performed intrathecally by spinal (lumbar) puncture performed in the L2-L3 gap, under local anesthesia with 1% lidocaine solution. The dose of autoCD34 + SC is determined by the content of CD34 + cells and is not less than 1x106 CD34 + cells per 1 injection. Autologous hematopoietic stem cells (HSC) obtained from the patient himself do not cause immunological conflicts, and, accordingly, do not require immunosuppressive therapy, unlike donor (allogeneic) and xenogenic cells. Thus, the patient does not experience disturbances in the natural mechanisms of anti-infectious and antitumor control. At the same time, autologous HSCs are relatively easy to obtain and cultivate if necessary, and when using this type of cells, doctors do not face ethical and legislative challenges.
Keynote Forum
Hatef Ghasemi Hamidabadi1
Mazandaran University of Medical Sciences, Iran
Keynote: Directed differentiation of Human Dental Pulp Stem Cells into mature cholinergic neuron using Cerebrospinal fluid: Mimicking stem cell niches
Time : 09:30 AM-10:00 AM
Biography:
Associate professor of Anatomy and cell biology at Mazandaran University of Medical science, Sari, Iran. I have subsequently taught all field of anatomy at the University up to now for medical students and other students, also my research field is stem cell differentiation in 2D & 3D cell culture into other subtypes of neurons like motor neuron, cholinergic neuron and especially dopaminergic neuron and its transplantation into ex vivo and in vivo/animal models.
Abstract:
Human Dental Pulp Stem Cells (hDPSCs) could be differentiated into cholinergic neurons under particular microenvironments. It has been reported that a wide range of factors, presented in Cerebrospinal fluid (CSF), playing part in neuronal differentiation during embryonic stages, we herein introduce a novel culture media complex to differentiate hDPSCs into cholinergic neurons.The hDPSCs were initially isolated and characterized. The CSF was prepared from the Cisterna magna of 19-day-old Wistar rat embryos (E-CSF). The hDPSCs were treated by 5% E-CSF for 2 days, then neurospheres were cultured in DMEM/F12 supplemented with 10-6 μm Retinoic Acid (RA), GDNF and BDNF for 6 days. The cells which were cultured in basic culture medium were considered as control group. Morphology of differentiated cells as well as process elongation were examined by an inverted microscope. In addition, the neural differentiation markers (Nestin, ChAT and MAP2) were studied employing immunocytochemistry. The genes ISLET1, Olig2, and HB9 were assayed by real-time PCR.Neuronal-like processes appeared during differentiation. Cholinergic neuron phenotype with ChAT and mature neural marker (MAP2) were expressed in treated group. In addition, motor neuron related genes were expressed in cholinergic neurons. Moreover Nissl bodies were found in the cytoplasm of differentiated cells.Taking these together, we have designed a simple protocol for generating cholinergic neuron using CSF from the human dental pulp stem cells, applicable for cell therapy in several neurodegenerative disorders.
Keynote Forum
Gennadii Bondariev
Institute of traumatology and orthopedics NAMS of Ukraine, Ukraine
Keynote: Regenerative medicine in orthopaedics and traumatology
Time : 10:00 AM-10:30 AM
Biography:
Gennadii Bondariev is a doctor orthopedist-traumatologist at the Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine, Scientific and Practical Center for Tissue and Cell Therapy since 2011. Leading orthopedic traumatologist at the Sandler Clinic. Deputy Head of the Association of Interventional Orthopedics and Traumatology of Ukraine. An author and co-author of many scientific works, including the introduction of new methods. He is engaged in conservative and surgical regenerative treatment of injuries and pathologies of the musculoskeletal system using a wide range of biotechnological products.
Abstract:
On the basis of the Scientific and Practical Center for Tissue and Cell Therapy of the Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine and the Sandler clinic, biotechnologies have been used to treat various injuries and pathologies of the musculoskeletal system since 2012. These are autologous concentrates of platelets, blood fibrin, mononuclear fraction of the bone marrow, medicinal signaling cells of the bone marrow and stromal-vascular fraction, as well as allogenic mesenchymal cells of the umbilical cord and placenta. This is mainly a conservative treatment using regenerative injection methods with ultrasound or X-ray navigation by introducing cellular products into joints, bones, intervertebral discs, ligaments, tendons and other structures of the musculoskeletal system. Besides there is also a high-precision intraoperative delivery of cells to hard-to-reach pathological areas, the use of autologous, allogenic and xenografts enriched with medicinal signaling cells for large defects of bone, cartilage or soft tissues. We also offer systemic intravenous administration of autologous and donor MSCs, purchases from different types of tissues for treatment of many orthopedic pathologies, including treatment of systemic diseases such as rheumatoid arthritis.
Keynote Forum
Shokoofeh Ghaemia
University of Tehran, Iran
Keynote: Inhibiting the expression of anti-apoptotic genes BCL2L1 and MCL1, and apoptosis induction in glioblastoma cells by microRNA-342
Time : 10:30 AM -11:00 AM
Biography:
Shokoofeh Ghaemi obtained her Master in microbiology from University of Tehran, Iran 2018 and now she is a Ph.D. candidate in University of Tehran. She has her expertise in evaluation and passion in improving the health and wellbeing also She is enthusiastic to use a variety of treatments using viruses to treat a variety of cancers. Her main research interests are cancer therapy, gene therapy and immunotherapy. in corona pandemic, she joined the research team that worked on mRNA vaccine against coronavirus and finally they published their results as an article. She has worked on cancer therapy using viruses.
Abstract:
Statement of the Problem: GBM (Glioblastoma multiforme) is a grade IV astrocytoma which is the most common type of malignant tumor in the brain. Originating from glial cells, it is an extremely aggressive and lethal type of brain tumor(1,2). Glioblastoma cannot be cured by current common methods. The most important obstacle to improving the therapy is that the central nervous system is heavily protected from systemic immune responses, which causes cancer cells to escape from the immune system and reduce systemic immune function(3,4). miRNAs are noncoding single-stranded RNA molecules of ~21–25 nucleotides in length. miRNAs regulate gene expression by targeting mRNAs, usually in the 3′ untranslated region (UTR), in a sequence-specific manner by triggering translational repression or mRNA degradation(5,6). Numerous miRNAs regulate programmed cell death including apoptosis, autophagy-associated cell death and necroptosis(7,8). Numerous miRNAs have been reported to perform specific effects in the regulation of tumor progression and multiple drug resistance(9,10). Some miRNAs can inhibit cancer cell motility and migration and suppress tumor cell growth(11–14). Taking all these into account, miRNA-mediated suppression of anti-apoptotic genes seems a promising strategy to induce apoptosis in cancer cells. Some of the anti-apoptotic genes are BCL2L1(also known as BCL-xl) and MCL1. BCL2L1 is located at 20q11.21 and MCL1 is located at 1q21.2 and belongs to BCL2 family. BCL2 family are regulator proteins that regulate apoptosis including anti-apoptotic and pro-apoptotic.
Keynote Forum
A Chapel
Institute of Radiological Protection and Nuclear Safety, France
Keynote: 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
Time : 11:00 AM - 11:30 AM
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 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 over dosages 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 scientific investigator of Clinical phase II trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdomino-pelvic complications refractory to standard therapy (NCT02814864Hirsch Index 29)
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.
Keynote Forum
Xiaobo Mao
Johns Hopkins University School of Medicine, USA
Keynote: Pathogenic α-synuclein cell-to-cell transmission mechanism and related therapeutic development
Time : 11:30 AM -12:00 PM
Biography:
Xiaobo Mao working at Johns Hopkins University School of Medicine, USA.Interested towards research in Stem Cell.
Abstract:
α-Synucleinopathies is characterized with accumulation of misfolded α-synuclein (α-syn), including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). Emerging evidence indicates that pathogenesis of α-synucleinopathies may be due to cell-to-cell transmission of prion-like preformed fibrils (PFF) of α-syn. We identified several receptors (Lag3, Aplp1, neurexins) that specifically bind with α-syn fibrils but not α-syn monomer. Lymphocyte-activation gene-3 (Lag3) exhibits the highest binding affinity with α-syn fibrils, and α-syn fibrils binding to Lag3 initiated pathogenic α-syn endocytosis, propagation, transmission, and toxicity. Lack of Lag3 (Lag3-/-) substantially delay α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. To determine the neuronal Lag3 and the function in mediating α-synucleinopathies in vivo, we obtained the neuronal Lag3 conditional knockout mice (Lag3n-/-) and found that Lag3n-/- can significantly reduce the behavioral deficits induced by α-syn PFF. Furthermore, we have generated the human dopamine neurons derived from induced pluripotent stem cells (iPSCs) and successfully generated the α-syn PFF model in human neurons. Moreover, we determined the LAG3 expression in human neurons. The LAG3 expression can be up-regulated by progerin, an aging inducer, and the higher LAG3 expression has been confirmed in aged mice compared to young mice. LAG3 inhibitors (anti-LAG3, compound) can inhibit the endocytosis of α-syn PFF and subsequent α-syn pathology propagation and toxicity. The identification of Lag3 that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.