Day 1 :
Keynote Forum
Joel Isaias Osorio Garcia
RegenerAge, USA
Keynote: The RegenerAge Combinatorial Bio-Interventions using Bioquantine® and allogeneic Mesenchymal Stem Cells combined with a spinal cord stimulation system in a No Option patient with ASIA-A classification
Time : 10:00-11:00
Biography:
Joel Isaias Osorio Garcia is the CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge™. He is also the Vice President of International Clinical Development for Bioquark, Inc., Founder and President for the Dr. Jois A.C initiative Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine. He is also the Visiting Scholar at University of North Carolina at Chapel Hill (Dermatology). Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.
Abstract:
In 1973 the American Spinal Injury Association made the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). In this clinical review our patient was classified after the vertebral fixation surgery with a ASIA-A scale injury after suffering a fracture and luxation at T-12-L1, having total spinal cord section. Based on the research made by Sergei Paylian, PhD on animal models and the safety use of allogeneic MSCs demonstrated on multiple animal models applications, we decided to apply a experimental translational medical protocol based the research and the previous outcomes obtained by Hamid and MacEwan and decided to customize it exclusively to our patient based on the clinical evidence and personalizing the therapy on evidence. The medical team designed an ambulatory method utilizing a C-arm to apply the allogeneic MSCs in situ and using a intrathecal (subdural) catheter using a slow pump release system for the rest of the biological material with an optimum tolerance and minor side effects (mild fever, miyalgias and headache) on the first 48 hrs hour after application. The experimental use of mRNA Bioquantine® was well tolerated with its purified form (intra and extra-oocyte liquid phases of electroporated oocytes) showing to be well tolerated by the patient without any anaphylactic reaction. The current clinical report is meant to demonstrate the beneficial changes with the use of Bioquantine® and its administration in a patient with a severe SCI offering a possible optional therapy and potential neuroregeneration in this clinical condition. Mesenchymal Stem Cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. The positive findings throughout the evolution of our protocol for spinal cord injury with the obtained results at this stage is a promising scientific based and evidence based medicine protocol that can be offered in the near future as an option for severe SCI patients. The functionality of the RestoreSensor® SureScan® by providing the electric stimulation fortifies the medical outcome and has given the patient the confidence to perform his physical rehabilitation with more energy for a longer time by the increase or decrease of the intensity of it according to the type of exercise regulated by the control-battery he handles. At this date, after 8 intrathecal applications of allogeneic MSCs and Bioquantine® in situ combined together we have got the following outcomes: an improvement in sensitivity, strength in striated muscle and smooth muscle connection by increased muscle mass and sphincter control, at 23 months after the first regenerative therapy and 12 months after the placement of RestoreSensor® the patient is showing an evident improvement on his therapy of physical rehabilitation (legs movement and control of them) having the following movements reported by the physical therapist: a) hip: adduction and external rotation, extension, abduction, internal rotation; b) knee: flexion; c) toe: MP and IP extension, also reporting an easier and functional crawling forward and backwards and since 3 months ago the patient is capable to stand on his knees for 2 or more minutes without any support and taking small steps on his knees forward and backwards for the first time in his process, showing a progressively important functionality on both limbs, voluntary movement at both feet and an increase in sensory perception. As we are probing in the case, combinatorial biologics can be used safely with other electronic disposals and bring a major benefit to SCI patients. With this unique combination we can give an option to those no option patients and create many more to improve patients quality of life.
Keynote Forum
Kristine Freude
BrainStem, Denmark
Keynote: Induced pluripotent stem cell models for Alzheimer's disease
Biography:
Kristine Freude is an Associate Professor at the University in Copenhagen and Director of the Center for Excellence in Neuroscience BrainStem. She has been at the University of California at Irvine, where she received her training in Stem Cell Biology funded by the California Institute for Regenerative Medicine (CIRM). Her current research is focused on disease modeling using induced Pluripotent Stem Cells (iPSC) from patients with neurodegenerative diseases such as Alzheimer's as well as CRISPR-Cas9 gene edited iPSCs carrying mutations associated with neurodegenerative diseases. Her research is funded by Innovation Foundation Denmark, Novo Nordisk Foundation and the Danish Alzheimer's Foundation.
Abstract:
Alzheimer’s Disease (AD) is the most common cause of dementia with currently no curative treatments available. To combat this disease it is crucial to understand the precise cellular disease pathology in order to define new targets for intervention. We have built a human induced pluripotent stem cell platform enabling us to study the disease mechanisms in the relevant target cells: human neurons, astrocytes and microglia. Our focus is on PSEN1, APP and sporadic forms of AD. For all of our lines with defined mutations we have generated CRISPR-Cas9 gene edited controls replacing the mutant nucleotide and generating isogenic controls. Our studies have so far revealed abnormal cristae formation in mitochondria accompanied by aberrant mitochondrial distribution and mitochondrial respiration deficiency. Other cellular phenotypes revealed abnormal ultrastructure’s of the Golgi Apparatus (GA), with shortened and dilated cisternae and increased surface area. The GA’s were scattered around the nuclei, indicating GA fragmentation. Furthermore reduced synaptic density and glutamine metabolic defects were part of the disease phenotypes. All of the observed cellular phenotypes were rescued in CRISPR-Cas9 generated isogenic controls, indicating a clear connection to the mutation. Moreover, mitochondria deficits, metabolic disturbances and synaptic deficiencies are considered early disease phenotypes, which can be recapitulated in our in vitro patient specific disease models making them attractive for drug target development for early interventions.
- Stem Cell Therapy | Regenerative Medicine | Mesenchymal Stem Cells |Tissue Bio-Engineering |Nanotechnology in Tissue Engineering|Induced Pluripotent Stem Cell | Skin Rejuvenation | Organ Regeneration
Location: Scandic Järvenpää | Helsinki, Finland
Chair
Joel Isaias Osorio Garcia
RegenerAge, USA
Co-Chair
Kristine Freude
BrainStem, Denmark
Session Introduction
Zaid Matti
Australasian Faculty of Musculoskeletal Medicine, New Zealand
Title: Platelet-rich plasma in musculoskeletal medicine
Biography:
Zaid Matti is a Musculoskeletal Medicine Practitioner. He has special interest in regenerative medicine with focus on ultrasound guided platelets rich plasma PRP and prolotherapy injections. He has completed his Graduation from the University of Baghdad Medical school in 2006. He has been trained in Orthopaedic Surgery at multiple hospitals in New Zealand and also had training in family medicine and emergency care. He is the Member of the Educational Committee of the Australasian Faculty of Musculoskeletal Medicine. He has completed his Post graduation study in Surgical Anatomy and Musculoskeletal Medicine from University of Otago in New Zealand.
Abstract:
Platelet-Rich Plasma (PRP) is one of many new developments within the field of regenerative medicine. Medical practitioners in areas such as musculoskeletal pain medicine, physical medicine and rehabilitation and rheumatology have been exploring the benefits of this novel therapy. The idea of using platelet-rich plasma in medicine has been around since the 1980’s. Its use has been employed in the area of musculoskeletal medicine recently in the past few years. Platelet-rich plasma in this field has received much media attention due to being used by many celebrity sports athletes for sports injuries. PRP is a promising treatment for some musculoskeletal conditions; However, evidence of its efficacy has been highly variable depending on the specific indication. Therefore, it is essential for practitioners to be aware of the concepts surrounding their use and application. The presentation will cover what platelet-rich plasma is? How is it prepared and administered? Its potential clinical application, and what the current literature discusses in the various areas of clinical musculoskeletal medicine and rehabilitation.
Omid Panahi
Yeditepe University, Turkey
Title: Nanotechnology, regenerative medicine and tissue bio-engineering
Biography:
Omid Panahi has completed his Graduation from Centro Escolar University on Doctor of Dental Medicien and MSc in Oral and Maxillofacial surgery from Yeditepe University, Istanbul, Turkey. He has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of ISI journals.
Abstract:
The Appearance of Regenerative Medicine (RM) and Tissue Engineering (TE) opened new areas in medical science. These rapidly expanded field focus on the restoring function of damaged tissues and organs. Due to their multidisciplinary identity, RM and TE are in close relationship with stem cell biology, cellular therapy, bioengineering and nanotechnology. The nanotechnology has provided new structure with special biochemical, mechanical and electrical properties. With the advancement in nanotechnology direct connection with cell has become possible which offers exciting possibilities in medical therapy.
Biography:
Purwati has completed her General Practition in Internal Medicine from Universitas Airlangga. She has also completed her Doctoral program from Universitas Airlangga. Her interest is in stem cell field. She has worked as a Secretary of Stem Cell Laboratory of Universitas Airlangga and also as a Secretary of Surabaya Regenerative Medicine Centre. She is currently the Chairman of Stem Cell Research and Development Center Universitas Airlangga, Surabaya, Indonesia. She has 60 publication in journals, papers.
Abstract:
Skin aging is natural process where renewal of skin cells and collagen production slows down, as well as the weakening of internal support structure and natural protective layer of skin. Several anti-aging therapies are widely used in dealing with aging. Stem cell metabolites are rich in growth factors such as cytokines IL-10, IL-4, EGF, GM-CSF and TGF-β. These cytokines can penetrate skin layer to stimulate the growth of new cells and increase nutrition, accelerate skin metabolism to inhibit premature aging, stimulate skin to produce new proteins, collagen and elastic fibers, also reduce black pigments. Previous research focuses on in vitro and animal study of stem cell metabolites derived from placenta for skin regeneration. This study is an advanced stage by focusing on clinical trial in 30 patients who met the inclusion and exclusion criteria to be applied with stem cell metabolites on their face. Subjects were examined their face conditions by using janus skin analyzer to see markers on their skin and applied stem cell metabolites in their face twice per day, at day and night with single-use doses of three pumping. Evaluation was carried out before and after application of stem cell metabolites using janus in six weeks. The results of janus examination evaluated were spot, pore, roughness, wrinkle, UV acne, UV spot and UV moisture. The percentage of spot, pore, roughness, wrinkle, UV acne and UV spots are decreased, while the percentage of UV moisture is increased in almost all subjects who were evaluated for six weeks. In qualitative, almost 90% subjects are satisfied with the results of the application of stem cell metabolites. The subjects felt that facial wrinkles were reduced, the face was smoother and supple and pigmentation was reduced. It can be concluded that stem cell metabolites formula are effective and efficient in skin regeneration.
Mirolyuba Simeonova Ilieva
University of Southern Denmark, Denmark
Title: Patients derived iPSC and brain organoids in translational psychiatric research
Biography:
Mirolyuba Simeonova Ilieva is a Cell Biologist and has completed her PhD in Bio-Medical Nanotechnology at the Danish Technical University. She is a Research Coordinator in the Patients Centered Laboratory of Translational Psychiatry. She is developing new scientific direction in the Department of Psychiatry, University of Southern Denmark-patients derived iPSC and brain organoids for modeling neurodevelopmental psychiatric disorders.
Abstract:
Since their discovery induced pluripotent stem cells (iPSC) offered a new highway for regenerative medicine and the development of new strategies for disease treatment. On the other hand, iPSC derived from patients with specific pathology gives new perspectives for elucidating intimate mechanisms of the disease and development individualized and more effective treatment. The biggest challenge for psychiatric research at present is the lack of an appropriate link between cellular and molecular findings with the clinical symptoms. An important aspect of understanding the neurobiology of psychiatric disorders is to test the utility of the findings in the diagnostic process, which may establish such findings as biomarkers. Therefore the development of new concepts for disease modeling in the field of psychiatry and the creation of relevant humanized in vitro models as a base for downstream research is of a high need. Brain organoids generated from iPSC recapitulate the dynamics of neurogenesis, cellular variety, and intercellular communication which are affected in neurodevelopmental psychiatric disorders such as autism. They have the ability to recreate the right complexity of the brain. On the cellular, protein and gene expression level, organoids demonstrate a high similarity to the neurodevelopment in vivo and can, therefore, recapitulate early stages of the neurogenesis. Brain organoids represent a new tool for high throughput screening of chemical compounds and move forward the development of individualized drug treatment. Finally, the same platform could be used in these individuals, who are at high risk for the development of psychiatric disorders and elucidate the etiology, based on risk factor genes.
Orianne Domenge
University of Lyon, France
Title: Chitosan physical hydrogels for the regeneration of infarcted myocardium
Biography:
Orianne Domenge has completed her Engineering degree in Chemistry and Process Engineering from CPE Lyon (Higher School of Chemistry, Physics and Electronics) and a Specialization in Biochemistry. She is currently pursuing her PhD in Biomaterials in IMP laboratory (Polymer Materials Engineering) and is working on the development of bio-functionalized polysaccharide patches in order to improve myocardial function after infarction.
Abstract:
Myocardial infarction occurs as a consequence of an obstruction of blood vessels supplying the heart (coronary arteries). This leads to the death of myocardial cells (cardiomyocytes). The damaged tissue does not repair spontaneously and scar tissue is formed instead, as the mature contracting cardiac cells have limited capacity to proliferate. The objective of this project is to develop bio-functionalized hydrogel patches that will allow regeneration and functional recovery of the cardiac muscle after myocardial infarction. The strategy is to associate polysaccharide-based hydrogels and trophic factors (proteins), so as to develop cardiac patches capable of inducing beneficial effects for tissue regeneration. More precisely, chitosan physical hydrogels were performed by a NaOH induced-gelation process. Thus, bio functionalized patches were produced varying in composition (polysaccharide concentration, degree of acetylation of chitosan, etc.) and characterized, in particular in terms of mechanical properties, as in the final application, gels will be sutured on the injured tissue. Cardiomyocytes were cultured in vitro on hydrogels to assess the effect of patch composition on the survival and proliferation of cells. Chitosan hydrogel patches were also tested in vivo using a rat model of myocardial infarction. Our results illustrate the beneficial effect of optimized chitosan hydrogel patches in the regeneration and functional recovery of the cardiac tissue after infarction.
Amod Kulkarni
University of Veterinary Medicine and Pharmacy in Kosice, Slovakia
Title: Mapping of binding sites on NadA protein of Neisseria meningitidis and blocking its interaction with human brain microvascular endothelial cells
Biography:
Nisseria meningitidis casing cererospinal meningitis utilizes several of its membrane proteins to interact with human Brain Microvascular Endothelial Cells (BMECs). Nisseria adhesin A -NadA an outer membrane protein has been recognized to mediate adhesion of bacteria and evokes strong bactericidal antibodies when used as vaccine candidate. In the present study, binding pockets of NadA (domains) interacting with the receptors of BMECs were mapped using mass spectrometry. In brief, binding of BMECs proteins and recombinant NadA (rNadA) expressed in E. coli M15 cells was determined by western blotting. On membrane tryptic digestion (partial) was performed and the non-interacting rNadA fragments were washed to retain BMEC protein-rNadA peptide complex. Further, mild striping was performed on the complex to isolate the domains of rNadA from BMEC proteins. MALDI-TOF/MS was employed to identify the amino acid sequences of the domains. Next, synthetically produced NadA peptides (37 mer peptides) corresponding to the interacting domains of rNadA were used to capture single domain antibodies (VHH) raised against rNadA through M13K07ΔpIII hyper phage system. At least 96 VHH clones were found to have an affinity for rNadA peptide 1 and 2. Among them 20 clones were tested for blocking the interaction of rNadA with BMEC proteins. However, only two clones of VHH binding to globular domain of rNadA and one clone of VHH binding to coiled coil region were able to block the interaction of rNadA with hBMEC proteins.
Abstract:
Amod Kulkarni has completed his PhD in Biosciences from Nord University, Bodo, Norway and has been a Postdoctoral Researcher at the Laboratory of Biomedical Microbiology and Immunology, UVLF, Kosice, Slovakia since April 2018. He has published his research in 15 papers in reputed journals and has been an active Researcher in the field of host-pathogen interactions.