Day :
- Adult Stem Cells | Bio Materials and Tissue Engineering | Stem Cell Niche | Stem Cell Biotechnology
Session Introduction
Todd K. Malan
Brigham Young University, USA
Title: Novel point of care, automated, and closed system for processing Stromal Vascular fraction either with or without Collagenase
Biography:
Todd Malan is considered one of the true pioneers of fat derived stem cell therapies in the USA. In October of 2009, Dr. Malan was the first U.S. physician to utilize adipose or fat derived stem cells for soft tissue reconstruction. He has described his techniques and experience as an author in two medical textbooks as well as having presented at dozens of stem cell conferences worldwide. Dr. Malan has been pivotal in developing safe protocols for stem cell harvesting and deployment for regenerative medicine and has trained hundreds of physicians worldwide in the safe and effective use of adipose derived stem cells. Dr. Malan began to seek out ways to utilize adipose stem cells for regenerative applications after a close family member was diagnosed with multiple sclerosis (MS). Dr. Malan now divides his practice time into cosmetic stem cell procedures and regenerative medicine research for patients with chronic disease and degenerative disorders
Abstract:
Stromal Vascular Fraction (SVF) is a component of lipoaspirate that can serve as a rich source of multipotent elements with phenotypic and gene expression profiles similar to human Mesenchymal stem cells (hMSCs) and Pericytes. SVF enriched fat grafts have demonstrated improved survival as compared to native fat as well as significant wound and scar healing properties. Currently a reliable, automated, and entirely closed point of care system for SVF processing technique does not exist. Here, we present the Q-Graft device from Human Med AG. The Q-Graft is an entirely closed and sterile point of care automated SVF processing device that can be used either with or without collagenase digestion. Adipose tissue is harvested directly into the device which is placed within the sterile OR field. The device then automates the incubation, filtration, washing, and suspension of the SVF pellet. We will present pre-clinical data gathered in our testing of the Q-Graft device to identify the cellular characterization of SVF product, growth kinetics and self-renewal assay, differentiation potential, ability to maintain sterility, and measures of residual collagenase. Comparisons will also be made in using the device either with or without collagenase.An evaluation as to the feasibility of direct point of care use of the Q-Graft device as an alternative to currently available manual and automated processing techniques will also be discussed.
Desiree Cox
Founder and CEO of Desiree Cox, UK
Title: New paradigm regulatory paradigms for cellular therapy and regenerative medicine
Biography:
Desiree Cox is Rhodes Scholar, educated at McGill University, Oxford University and Cambridge University. She has rightly earned her place as a Thought-Leader in healthcare and education and is highly respected health consultant internationally. Her focus is on health innovation, the regulatory aspects of the global stem cell and regenerative medicine, and medical tourism. Dr. Cox has 20+ years in the healthcare field with an impressive career and a rare and unique range of skills and capacities gained from a career that has spanned clinical medicine, academia, research and development, regulatory sciences, health and social enterprise. She has worked in the UK, US, Canada and The Bahamas. Her experience in healthcare consulting includes consulting for biotech companies and major pharmaceutical companies including Amgen, GSK, and Novartis on pipeline therapeutic products and medical devices. Since 2015 she has been spearheading health innovation in The Bahamas and the development of the stem cell and regenerative industry in The Bahamas. She is the Founder and CEO of The HEALinc Health Innovation Incubator (www.thehealinc.com). She is also a Singularity University Social Impact Fellow and Ambassador/License-holder of the recently launched SingularityU Nassau Chapter fostering the use of accelerating/exponential technologies
Abstract:
Great successes in the prevention and treatment of a multitude of diseases have been achieved through the use of pharmacological drugs that target cellular receptors to alter human physiology. Breakthroughs in science of cell therapy and regenerative medicines have led to tremendously promising novel therapies that will likely change the paradigm of medicine and health for decades to come. However, unlike therapies commonly used today, these novel regenerative medicine therapeutics including stem cells and gene editing will likely permanently alter tissue structure and function. Consequently, the likely permanence of regenerative medicine therapeutics combined with the growing number of patients who choose to receive medical therapy outside of their home country (medical tourism) and increased accessibility of regenerative medicines for patients is ushering in a new era of challenges for bioethics and regulatory sciences.We need a new paradigm for collaboration involving all aspects of the production, manufacture, research and clinical application of gene and cellular therapies. In this presentation, we will discuss several paradigms and approaches for the design, development and implementation of a more collaborative, modern, holistic global regulatory framework. We will focus on the case study of the regulatory framework in The Bahamas as an example of an ethical model for evaluating, monitoring safety and efficacy of advanced cellular therapies. We argue that there is a need for more inclusive perspectives, broader adoptions, and swifter, more efficient implementation strategies in the interest of furthering an improved educational bedrock and advancing the field. Our hypothesis and analysis suggests that a more integrative and unified regulatory landscape will likely require a multi-disciplinary approach that leverages advances in accelerating technologies and systems-thinking in order to capture and share clinical outcomes across many different geographies and regulatory jurisdictions. It will also require us to draw on diverse experiences and ethical models in order to overcome bureaucracy and make promising gene and cellular therapies more widely accessible and cost-effective
José Manuel Baena
BRECA Health Care and REGEMAT 3D, Spain
Title: 3D printing technologies applied to Medicine and Regenerative Medicine
Biography:
José Manuel Baena, research associate "Advanced therapies: differentiation, regeneration and cancer" IBIMER,CIBM, Universidad de Granada Founder of BRECA Health Care, pioneer in 3D printed custom made implants for orthopedic surgery, and REGEMAT 3D, the first Spanish bioprinting company. Expert in innovation, business development and internationalization, lecturer in some business schools, he is passionate about biomedicine and technology. In his free time he is also researcher at the Biopathology and Regenerative Medicine Institute (IBIMER). -MSc. José Manuel Baena, Global biotech entrepreneur, research associate at the Advanced therapies: differentiation, regeneration and cancer group of the UGR. Holds a degree in Industrial Engineering from the Polytechnic University of Valencia (Spain) and a Postgraduate Degree in Mechanical Engineering from TU Braunschweig (Germany). Jose Manuel is working in biomedical engineering since 2008, after attending a postgraduate course on Biomechanical Engineering at the University of Buenos Aires (Argentina). He is also MSc in Motorsport Engineering from Oxford Brookes University, UK and a PhD candidate in Biomedicine (expected 2016). His career in R&D project management and Executive Management will provide the knowledge necessary for proper implementation and development
Abstract:
Traditional manufacturing techniques are based on the subtraction of material from a raw block or on modifying the shape by means of an external power source and shaping it using a mold.3D printing (3DP), AM, rapid manufacturing….are based on the principle of adding material layer by layer allowing the manufacture of complex external and internal shapes with a mesh structure (scaffold. Craniosynostosis is a condition in which one or more craneal sutures close prematurely, impeding the normal development of the brain and changing the normal bone grow pattern. As a result patient that suffer from this condition have large bone defects.Our mission is to develop innovative solutions in the area of bioprinting and regenerative medicine towards the clinical application of this amazing technology, aiming at improving people´s quality of lifePrint 3D multi component parts with different materials with a customized external shape and an internal mesh structure that mimic human living tissues.
Walter Bini
Universidad de Zaragoza-UAE
Title: Degenerative disc disease: up-front considerations regarding lumbar mesenchymal cells
Biography:
Walter Bini has completed his Diploma at Westminster School, Simsbury Conn. USA andPost-graduate degree at Universidad de Zaragoza, Facultad de Medicina, Zaragoza-Spain. In 2014, he was the Middle East Chairman of ISLASS. He was Head of Neurosurgery at Sheikh Khalifa General Hospital, UAQ-UAE from 2014- 2016. Currently, he is Consultant Neurosurgeon in Orthopedic department, spine section of Lanzo Hospital COF, Lanzo d’Intelvi in Italy and also Visiting Consultant Neurosurgeon in Orthopedic department at Healthpoint Hospital, UAE
Abstract:
Treatment with mesenchyme adipose tissue derived stem cells Lumbar degenerative disc disease poses an on-going challenge as far as treatment options and alternatives, especially when considering younger patients. Over 80% of the adult population presents with one or more episodes of on-going-progressive low-back pain .The primary cause is associated with degeneration of the intervertebral disc and which is triggered by a decrease of the nucleus pulpous cell population, as evidenced in histological studies. Definitely, in the presence of a "black disc" without profusion and neurological compromise, microsurgery or even fusion surgery should not be contemplated. Numerous percutaneous techniques have been propagated as proper way to treat this condition throughout the literature in the past years. They have been primarily focused on the treatment of the pain generated by the involved disc and the subsequent segmental insufficiency, without addressing the degeneration of the disc and for this have had limited success and remain as pain management tools. Some significant trials in the past ( i.e. Chondrocyte transplantation trial ) and the increasing recent research and achievements with more biological strategies as far as tissue regeneration , have motivated the development of a new treatment concept initially applicable to the lumbar spine which will be presented and discussed.Advancements have led to a significant improvement in the understanding of the cell environment and tissue transplantation at a molecular, cellular and immunobiological level. Adipose tissue has already become a central source of clinical and research work involving adipose tissue derived progenitor cells. Endothelial and mesenchyme stem cells derived from adipose tissue are being considered and used in an array of clinical conditions and seem to have clear therapeutic benefits for many disease conditions including those affecting bone, cartilage and muscle . The use of an accessible source with abundant cells which have a high potential for regeneration clearly is superior in comparison to the chondrocyte option for the lumbar disc. Mesenchymal cells have a high self-renewal capacity and a potential for multi lineage differentiation. For this , adipose tissue derived MSCs ( ADMSCs) are optimal candidates for tissue regeneration and can be obtained from the patient in a one-step procedure-treatment
Michele Zocchi
University of Turin- Italy
Title: A New global platform for regenerative technologies
Biography:
Michele Zocchi graduated in Turin in 1976. He lived for over ten years abroad, first in the United States and then in France to obtain specialties in maxillofacial surgery and in plastic and aesthetic surgery. He has worked and works as an in-house doctor and as a researcher in the most prestigious institutions worldwide, mainly in Brazil, Spain, France and the United States. Today the prof. Zocchi is recognized among the pioneers and among the most authoritative professional figures in the world in the field of body contouring surgery, of the physio-pathology of adipose tissue and of tissue regeneration. Since 1988, with his return to Italy, he has focused his professional interest especially in the field of lipoplasty and liposculpture, providing a fundamental contribution to the research and development of new methodologies and new surgical protocols, inventing and refining the related instruments. Among others, ultrasound lipoplasty , bicompartmental lipostructuring of the breast and the production of adult mesenchyme stem cells from adipose tissue aimed at tissue regeneration stand out . In his career, prof. Zocchi has carried out more than ten thousand surgical operations, while at the same time conducting an intensive congress and teaching activity in university institutes and educational programs. He has been speaker and guest of honor in over 400 international congresses in more than 40 countries. He is the author of over 150 books, monographs and publications on the most prestigious international journals in the sector. He is an effective or honorary member of more than 20 international surgical societies and professional associations. He holds the position of scientific director, responsible coordinator and teacher in charge of the permanent training program (PFP) of the Italian Society of Plastic, Reconstructive and Aesthetic Surgery. He is National Delegate for Italy of Espras (European Confederation of National Plastic Surgery Societies). He is fluent in Italian, English, French, Spanish and Portuguese
Abstract:
Remix is a global international platform finalized to identify, analyze and select cutting edge technologies in each specific field of Regenerative Medicine and Surgery for merging with the most efficient Protocols and Guide Lines tailored for every clinical need and every anatomic district. The main concept behind this new philosophy is that a "Custom Made Regenerative Mixture" (REMIX stands for Regenerative Mixture) containing multiple components is way more effective in inducing and supporting regenerative processes than a single component implant. In the REMIX protocols we find Perycites and Cells Precursors from the freshly insulated A.T. Stromal Vascular Factor, Growing Factors from Blood Derivates (not simple PRP but PRGF or PL) and some other specific and a specific Bio Catalyzers, including Bioactive Proteins, Amino Acids and Vitamins.The rational sustaining the use of Bio Catalyzers is that whenever it is desirable to naturally stimulate and accelerate the process of cell’s recruitment toward some specific cellular lines or to better support the cell’s intake in the recipient site it is possible to add to the Regenerative Mixture some specific or aspecific components acting as Bio Catalyzers. The most valuable Bio Catalyzers are: Bioactive Proteins (BP), Amino Acids (AA) and Vitamins (VIT)
Helen Wheadon
University of Glasgow –UK
Title: The Role of bone marrow morphogenic signals in sustaining chronic myeloid leukaemia
Biography:
Helen completed her PhD in 1997 at University College London. Her career then consisted of postdoctoral studies at the University of Bath, an MRC fellowship, followed by a tenured position at the University of Ulster. She is currently a senior lecturer at the University of Glasgow with expertise in stem cell signal transduction specialising in leukaemia research. She is also Associate Dean of Post-graduate Research within the College of Medical, Veterinary and Life Sciences at the University of Glasgow. She has published more than 25 papers in reputed journals and regularly reviews papers, grants and serves on editorial boards. She is active in promoting public understanding of stem cells and Bioethics surrounding the use of stem cells and animal models in science
Abstract:
Chronic myeloid leukaemia (CML) results from a genetic change in a haemopoietic stem cell (HSC), leading to a hierarchical clonal stem cell disease, with the expanding leukaemic stem cell (LSC) population sustaining the malignancy within the bone marrow (BM) niche. The cells express the constitutively active tyrosine kinase BCR-ABL, which causes rapid cell division and leukaemia. Therapy involves tyrosine kinase inhibitor (TKI), which effectively inhibits BCR-ABL, thereby controlling CML. However, TKI doesn’t eliminate the LSC population; therefore patients are not cured and require life-long therapy. This phenomenon of disease persistence under therapy, suggests BCR-ABL-independent mechanisms are being exploited to sustain the survival of LSC. Increasing evidence suggests that the BM microenvironment plays a pivotal role in the initiation and progression of the leukaemia. Of particular interest are the morphogens, growth factors implicated in embryogenesis, developmental haemopoiesis and homeostasis. Microarray analysis, comparing chronic phase (CP), accelerated phase (AP) and blast crisis phase (BP) CML LSCs and progenitor populations to normal HSCs and progenitors, indicated that the Notch, Wnt, TGFbeta superfamily and Hedgehog (Hh) pathway are highly deregulated in CML. To investigate this further, we profiled mesenchymal stem cells (MSCs) from normal donors and CML, CP (n=12), myeloid BP (n=11), and lymphoid BP (n=5) stem and progenitor populations, for gene components of Wnt, Notch, Hedgehog, and BMP pathways. Data indicates that self-renewal pathways were highly deregulated between CP and BP with statistically significant upregulation in Wnt components in myeloid BP compared to CP. Targeting the pathways using small molecule inhibitors indicate that the BMP, Hh and Notch pathways are viable therapeutic targets in combination with TKI and that Wnt upregulation is preventing Notch activation in myeloid BP-CML. These findings highlight the complexity of self-renewal pathway interaction especially in progressive disease.
Ivana Haunerová
State Institute for Drug Control, Czech Republic
Title: Stem cell based medicinal products from a regulatory view
Biography:
Ivana Haunerová is a Quality Assessor for biotech and advanced therapy medicinal products in the State Institute for Drug Control in the Czech Republic. She has completed her graduation in Biochemistry at the Institute of Chemical Technology, Prague. Since 2009, she is a Member of the Committee for Advanced Therapies at EMA
Abstract:
Stem cell based advanced therapy medicinal products offer big hope for patients that currently have no alternative efficient therapy. The patients are even willing to travel outside the EU for stem cell based treatments. However, there are considerable potential risks linked to the usage of this type of products. Therefore, it is a legal and regulatory challenge to establish rules that enable rapid development of safe and effective medicinal products. New regulatory procedures have been introduced in the EU to support and accelerate the development of medicinal products. Currently, there is a high number of stem cell based medicinal products in the clinical phase of development. However, till now only two of them gained an approval of the centralized marketing authorization application. The development of stem cell based products requires very good strategy planning via using a risk-based approach based on multidisciplinary evaluation. Additional aspects such as future logistic activities with respect to the potential market or technical possibilities should be considered. Especially for academia which is involved in this field it can be an enormous load and therefore the awareness of potential pitfalls and the knowledge of regulatory procedures (such as scientific advices, certification, PRIME and others) that could facilitate a development is essential.
Pedro Morouço
Polytechnic Institute of Leiria, Portugal
Title: Four-dimensional bio printing: stimuli-responsive mechanisms for regenerative medicine
Biography:
Pedro Morouço is a very enthusiastic and provoking early-career researcher. Currently, is the Head of R&D Bio fabrication Group at the Centre for Rapid and Sustainable Product Development – Polytechnic Institute of Leiria, Portugal. He is the Principal Investigator of “2bio4cartilage – Integrated intervention program for prevention and treatment of cartilage lesions”, and his research activity focuses, mostly, on products and processes engineering, aiming to bringing the gap between the lab and in vivo applications. In the last years, he has been invited to collaborate in several national and international projects, he has co-edited books, authored and co-authored more than 200 scientific works, is member of the scientific committees in various conferences, member of the Advisory Board on TERM for Cambridge Scholars Publishing, and editorial member and reviewer of various journals. Finally, Pedro is aware of the role of science for society awareness. Thus, he developed skills to be able to reach wider audiences (2 awards in the National Science Communications Contests and representative of Portugal in an international event, Winner of The Publishing Method competition by the American Journal Experts, 2017, was distinguished with the New Investigator Award 2014 and Hans Gros Emerging Researcher Award 2017 from ISBS, Prestigious Award 2017 by the Leiria City-hall and named one of the Personalities for 2017 by the regional press
Abstract:
Three-dimensional (3D) bio printing emerged has a highly versatile technology able to produce customized structures. The ability to produce those structures in a layer-by- layer fashion allowed a precise control over geometry, morphology and pore interconnectivity. However, those 3D structures may not be the most suitable approach for the clinical requirements. Indeed, four-dimensional (4D) bio printing seems to promise a technology with the ability to induce planned changes at the structures, bridging the gap between the laboratorial constructs and the native human tissues. In summary, 4D bio printing main goal is to develop biological 3D structures, which are suitable to change their properties (e.g. stiffness, shape, volume) when triggered by a pre-defined stimulus (e.g. electricity, ionic force, light, magnetic field, pH and temperature). If on one hand it is important to develop and design new materials and processes, on the other hand making those materials biocompatible is also crucial. The audience will be dared to think further on the applications of this technology. How will the stimulus be provided? By who? And on which conditions, are some of the topics which will be addressed
Bianca Marchetti
University of Catania Medical School, Italy.
Title: Therapeutic potential for somatic neural stem cell (nsc) grafts in the restoration of midbrain dopaminergic neuronal function in the aged parkinsonian brain
Biography:
Bianca Marchetti has completed her PhD in 1987 from Laval University, Quebec, Canada, and postdoctoral studies from McGill University. She is full Professor of Pharmacology at the University of Catania, Medical School and directs the Laboratory of Neuropharmacology at the OASI Scientific Institute for Research and Care (IRCCS) on Mental retardation and Brain Aging of Troina (EN), Italy. She has published more than 100 papers in reputed journals and has been serving as an editorial board member of neuroscientific journals..
Abstract:
Parkinson’s disease (PD) is the most prevalent central nervous system (CNS) movement disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons of the substantia nigra pars compacta (SNpc). The causes and mechanisms leading to mDA neuron demise in sporadic PD remain poorly understood, but current evidence indicates that they depend on a complex interaction of genetic susceptibility, environmental factors and, most importantly, aging and inflammation. Particularly, reactive astrocytes (Ras) are key players in the response to PD injury and inflammation, via Wnt/β-catenin signalling, regulating both helpful and harmful responses. Because aging is the chief risk factor for PD development, we focused on the aged male midbrain microenvironment to address the ability of neural stem progenitor cells (NSCs) to activate intrinsic cues that may instruct midbrain astrocytes to implement mDA neurorepair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced long-lasting DA neurotoxicity. Here, we discuss our recent data showing that subventricular zone (SVZ)-derived adult NSCs transplanted in the aged MPTP-injured SNpc promote a remarkable time-dependent endogenous nigrostriatal DA neurorestoration. Although multiple modes of reciprocal interactions between exogenous NSCs and the pathological host milieu may underlie the functional improvement observed, our data suggest that NSCs and astrocyte-derived factors, especially Wnt1, might play a major role acting at different levels to rejuvenate the host microenvironment and promote mDA neurorepair/regeneration. In light of the emerging picture implicating deregulated Wnt/β-catenin signalling in PD, our findings predict a novel perspective on harnessing Wnt/β-catenin signalling with functionally plastic NSC grafts as a novel therapeutic strategy for PD
Pradeep .V. Mahajan
StemRx Bioscience Solutions Pvt. Ltd., India
Title: Biological plastics: future revolution in medicine
Biography:
Mahajan completed his post-graduation in General Surgery from Marathwada University, Maharashtra and went on to pursue Diploma in Urology at the University of Vienna, Austria. In a career changing move, after three decades of being a successful general and uro-surgeon, he started his brainchild-StemRx Bioscience Solutions Pvt. Ltd. in the year 2011. This was to focus on in-depth research in the field of Regenerative Medicine and Cell Based Therapy which he believes is the solution to address the limitations of conventional therapeutic modalities. To this effect, he underwent and continues to undergo intensive training in the field at both national and international levels. He has devised personalized treatment protocols in cell based therapy for more than 75 health conditions. Dr. Mahajan is a Life member and Joint Secretary of The Stem Cell Society of India as well as Vice President of Anti-Aging Foundation, Delhi and Scientific National Advisor, Indian Stem Cell Study Group. He has been appointed as Hon. Associate Professor of Regenerative Medicine and Cell Based Therapy at Dr. R N Cooper Hospital, Mumbai and Faculty for MD Transfusion Medicine at KEM Hospital, Mumbai. Dr. Mahajan’s academic collaborations include those with the Maharashtra University of Health Sciences and ITM University.
Abstract:
The term ‘plastic’ is often associated with synthetic materials that can be molded or shaped and can be used to improve appearance or function of materials. Even in medicine, synthetic plastics are being used in fabrication of disposable delivery devices, scaffolds, artificial organs etc. Nonetheless, most plastics are considered non-biodegradable and non-living thereby lacking interaction with local and systemic environment. This raises questions regarding their safety and efficacy in the long term. Currently, the new keyword in medicine is ‘Biological Plastics’ that are evolving at a rapid rate and aim to find solutions to address limitations of conventional medicine. ‘Biological Plastics’ are those that exist in the human body; namely cells, growth factors, scaffolds and their products including cytokines, chemokines and matrices. Of these various agents that are capable of repair, regeneration and rejuvenation of organs and tissues of the body, the most promising are Mesenchyme Stem Cells (MSC) which may be called ‘The Living Drug’ molecule. There is a paradigm shift in the way diseases are now being viewed owing to enhanced knowledge of these molecules. The possible therapeutic applications of cell based therapy are limitless and it is now important to involve interdisciplinary sciences in order to enhance efficacy of these biological plastics. With the advent of MSCs and knowledge about their plasticity, various classical dogmas have been challenged. Through this presentation, the aim is to explain the properties of these ‘Biological Plastics’ and their applications in myriad of health conditions
Frank J.T. Staal
Leiden University Medical Center -Netherlands
Title: Stem cell based gene therapy for Recombinase deficient-SCID
Biography:
Frank Staal’s research is centred around the differentiation of blood-forming stem cells (hematopoietic stem cells, HSCs) to the major disease fighting white blood cells The research of Frank J.T. Staal focuses on molecular regulation of immature T lymphocyte development and hematopoietic stem cell biology. Besides basic aspects of transcriptional regulation and cell signalling in mouse and human, this knowledge is applied to diagnosis and gene therapy applications of primary human immunodeficiencies as well as to abnormal lymphoid development in acute lymphoblastic leukemias. Translational research leading to novel diagnostic and therapeutic tools is an integral part of his research activities
Abstract:
Recombinase-activating gene (RAG) deficient SCID patients lack B and T lymphocytes due to the inability to rearrange immunoglobulin and T-cell receptor genes. The two RAG genes are acting as a required dimer to initiate gene recombination. Gene therapy is a valid treatment alternative for RAG-SCID patients, who lack a suitable bone marrow donor, but developing such therapy for RAG1/2 has proven challenging.Hence, we tested clinically relevant lentiviral SIN vectors with different internal promoters (UCOE, PGK, MND, and UCOE-MND) driving codon optimized versions of the RAG1 or RAG2 genes to ensure optimal expression. We used Rag1-/- or Rag2-/-mice as a preclinical model for RAG-SCID to assess the efficacy of the various vectors at low vector copy number. In parallel, the-conditioning regimen in these mice was optimized using busulfan instead of commonly used total body irradiation.We observed that B and T cell reconstitution directly correlated with RAG1 and RAG2 expression. Mice receiving low Rag1/2 expression showed poor immune reconstitution; however high Rag1/2 expression resulted in a lymphocyte reconstitution comparable to mice receiving wild type stem cells. Efficiency and safety of our clinical RAG1 lentivirus batch was assessed in Rag1-/- mice model showing that functional restoration of RAG1-deficiency can be achieved with clinically acceptable vectors. Additionally, RAG1-SCID patient CD34+ cells transduced with our clinical RAG1 vector and transplanted into NSG mice led to fully restored human B and T cell development. Together with favourable safety data, these results substantiate a clinical trial for RAG1 SCID which is planned for late 2018.
- Mesenchyme Stem Cells| Regenerative Medicine | Stem Cell Therapy| Stem Cell Technologies
Session Introduction
Robert J. Hariri
Celularity Inc, USA
Title: Decellularized human placenta for tissue and tissue and organ regeneration
Biography:
The Founder and CEO of Celularity, Inc., Dr. Hariri is a surgeon, biomedical scientist and highly successful serial entrepreneur in two technology sectors: biomedicine and aerospace. The former Chairman, Founder, and Chief Executive Officer of Celgene Cellular Therapeutics, one of the world’s largest human cellular therapeutics companies, Dr. Hariri has pioneered the use of stem cells to treat a range of life threatening diseases and has made transformative contributions in the field of tissue engineering. He co-founded Human Longevity, Inc, the world’s largest gene sequencing operation with genomics legend, J. Craig Venter and Xprize founder Peter Diamandis and serves as Vice Chairman. Dr. Hariri has over 150 issued and pending patents, has authored over 100 published chapters, articles and abstracts and is most recognized for his discovery of pluripotent stem cells from the placenta and as a member of the team which discovered TNF (tumor necrosis factor). Dr. Hariri was recipient of the Thomas Alva Edison Award in 2007 and 2011, The Fred J. Epstein Lifetime Achievement Award and has received numerous other honors for his many contributions to biomedicine and aviation
Abstract:
Recellularization of organ derived decellularized native and functional vasculatures with stem cells or tissue specific cells have been regarded as a viable approach to engineer organ to overcome donor shortage in organ transplantations. Human placenta is a large viable organ with abundant vasculatures and variety of hematopoietic stem cells and non-hemapotietic stem cells. To take advantage of this easily obtainable resource, we explore the feasibility of using human placenta’s vasculature as a suitable source for tissue and organoid engineering. We developed a proprietary method of sequential detergent based perfusion process to decellularize an entire human placenta as well as single placenta cotyledons. We demonstrated that the decellularized placenta or single cotyledon maintain efficient circulation and are able to conduct fluid and distribute cells, indicating that the vasculature system remained intact and functional after decellularization. The decellularized human placental vasculature scaffold (DHPVS) were shown to support in vitro proliferation and function of cells derived from multiple tissues including human placental adherent cells (PDAC®), primary hepatocytes, thyroid tissue epithelial cells, insulin producing cells and endothelial cells for 3 weeks. PDAC® grown on DHPVS demonstrated enhanced adipogenic differentiation comparing with 2-D culture when exposed to adipogenic induction culture medium. Furthermore, PDAC® transduced with Luciferase grown on DHPVS were shown to maintain viability for 4 weeks after subcutaneously implanted in mice. These in vitro and in vivo data provide evidences that decellularized human placenta vasculature can support cell growth and differentiation and can be used as a scaffold platform for tissue and organ engineering
Lucie Bacakova
Czech Academy of Sciences, Czech Republic
Title: Adult stem cells in bone and vascular tissue engineering – a review
Biography:
Lucie Bacakova, MD, PhD, Assoc. Prof. has graduated from the Faculty of General Medicine, Charles University, Prague, Czechoslovakia in 1984. She has completed her Ph.D at the age of 32 years from the Czechoslovak Academy of Sciences, and became Associated Professor at the 2nd Medical Faculty, Charles University. Since 2005, she is the Head of the Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences. She is a specialist for studies on the interaction of differentiated and stem cells with various biomaterials, and for vascular, bone and skin tissue engineering. She has published more than 160 papers in reputed journals.
Abstract:
Adult stem cells, i.e. stem cells derived from various tissues of the adult organism, are promising for cell therapy and tissue engineering. These cells overcome the ethical and legal issues associated with the use of human embryonic and fetal stem cells, and also enable the use of autologous stem cells for the implantation into patients. Human bone marrow mesenchyme stem cells (bmMSCs) have been widely used and even applied in numerous clinical trials, e.g. for treatment of critical limb ischemia during diabetes [1], lower limb long bone nonunion [2] or neurological diseases [3]. Recently, another promising source of mesenchyme stem cells emerged, namely adipose tissue. In comparison with the bmMSCs, the adipose tissue-derived stem cells (ASCs) are available in larger quantities and by less invasive approaches, such as liposuction. Although ASCs were discovered relatively recently, in 2002 [4], they have been relatively widely clinically applied in human patients, particularly for reconstructive, corrective, aesthetic and cosmetic purposes [4, 5]. In our studies, we attempted to differentiate human ASCs, isolated from lipoaspirates obtained by liposuction, towards osteoblasts (Ob) and vascular smooth muscle cells (VSMCs). For differentiation towards Ob, the ASCs were seeded on chitosan/glucan/hydroxyapatite and cultivated in an osteogenic medium supplemented with ascorbic acid, β-glycerophosphate and dexamethasone. In comparison with commercially available human bmMSCs, the ASCs produced similar amounts of type I collagen and Runx2, i.e. early markers of osteogenic differentiation, but lower levels of osteocalcin, a late marker of osteogenic differentiation [6]. For differentiation towards VSMCs, the ASCs were cultivated in a medium supplemented with transforming growth factor-ß1 and bone morphogenic protein-4. This medium induced the appearance of alpha-actin, calponin and myosin heavy chain, i.e. an early, intermediate and late marker of VSMC differentiation, respectively, in ASCs, and the amount and intensity of fluorescence of these markers were further enhanced by cultivation in a lab-made pressure-generating dynamic cell culture system. Thus, ASCs appears to be more suitable for vasular tissue engineering than for bone tissue engineering.
Mohammad Hasan Sheikhha
Shahid Sadoughi University of Medical Sciences, Iran
Title: Mitochondrial DNA deletions and telomere shortening during multiple passages of dental pulp stem cells (DPSCs), periapical follicle stem cells and human foreskin fibroblast cell line
Biography:
Mohammad Hasan Sheikhha has completed his PhD in 2002 from Manchester University, UK. He is the president of International Campus, Shahid Sadoughi University of Medical Scienecs, Yazd, Iran. He is workind as professor of medical genetics and has published more than 100 papers in reputed journals and has been serving as an editorial board member of International Journal of Reproductive Biomedicine
Abstract:
Limited resources for adult stem cells necessitate there in vitro culture prior to clinical use. Investigating mitochondrial DNA (mtDNA) and telomere shortening has proved to be important indications of stem cell validity. This study was designed to investigate these indicators in multiple passages of three adult stem cell lines which were produced in our stem cell laboratory.In this study, Dental Pulp Stem Cells (DPSCs), Periapical Follicle Stem Cells (PAFSCs) and Human Foreskin Fibroblast (HFF) cell lines were expanded for 20 passages. After 1, 5, 10, 15 and 20 passages, expanded cells were harvested and DNA was extracted for further studies. Common mtDNA mutation was detected by multiplex PCR and telomere shortening was tested by Southern blot analysis. The common deletion was not detected in any of the stem cells or cell lines after several passages. In addition, Southern blot analysis indicated that the mean difference of telomere length between first and last passage was 0.25 kb in DPSC, 0.1 kb in PAFSC and 0.32 kb in HFF which indicates that the mean telomere length in various passages of the samples showed insignificant changes.Absence of mtDNA mutations in adult stem cell lines indicates good mitochondrial function even after 20 passages. In addition, absence of telomere shortening indicates stem cells validity after multiple passages. It is hoped this information could pave the way for using in vitro expansion of adult stem cells for future clinical applications.
Sameh K Sadek
University of Alexandria, Egypt
Title: Platelet glycoprotein iib/iiia polymorphism and its role in recurrent early pregnancy loss
Biography:
Sameh k sadek is Associates Professor in university of Alexandria and hé is member of Clinical pathology Department, Faculty of Médicine, and Alexandria University. He completed his PHD on infertility pregnancy and he is Assistant Professor in Gynaecology department in Alexandria. He has done nearly 25 publications and went to many summits as guest speaker.
Abstract:
Recurrent pregnancy loss (RPL) is one of the Most frustrating and difficult areas in reproductive medicine because the etiologic is often unknown and there are few evidence-based diagnostic and treatment strategies. RPL is defined as two or more failed clinical pregnancies as documented by ultrasonography or histopathology examination.(2) Approximately 15 percent of pregnant women experience sporadic loss of a clinically recognized pregnancy. Just 2 percent of pregnant women experience two consecutive pregnancy losses and only 0.4 to 1 percent have three consecutive pregnancy losses. Couples who have had a pregnancy loss have two major concerns: the cause and the risk of recurrence. Unfortunately, the cause of RPL can be determined in only 50 percent of patients. General etiological categories of RPL include anatomic, immunological, genetic, endocrine, thrombophilia, and environmental factors. Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis.(5,6) A significant proportion of the population has a detectable abnormality in blood, but most of these only develop thrombosis in the presence of an additional risk factor. The human glycoprotein (GP)IIb/IIIa is one of the best characterized receptors present on the surface of platelets.(7) GPIIb/IIIa belongs to the large family of adhesion molecules called integrins, which share a common heterodimeric structure. The primary function of GPIIb/IIIa is to aid platelet aggregation.(8) Nearly 20 years ago, Savage et al. demonstrated that the GPIIb/IIIa on the membrane of nonactivated platelets serves as a specific receptor for surfacebound fibrinogen(9) but, after platelet activation(10) this receptor acquires the ability to interact with other adhesive proteins, such as vitronectin, fibronectin and von Willebrand factor