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Overview | Speakers | Venue | Sponsors | Poster Submissions


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Day 1 Day 2
Day 1 - Monday, April 25, 2016
7:00 Registration & Continental Breakfast
Keynote Presentation
Moderator: Robert Halliwell, University of the Pacific
8:00 iPS Cell Technology and Disease Research
Rudolf Jaenisch

Founding Member, Whitehead Institute Professor of Biology
Massachusetts Institute of Technology
  The development of the iPS cell technology has revolutionized our ability to study human diseases in defined in vitro cell culture systems. A major problem of using iPS cells for this “disease in the dish” approach is the choice of control cells because the unpredictable variability between different iPS / ES cells to differentiate into a given lineage. Recently developed efficient gene editing methods such as the CRISPR/Cas system allow the creation of genetically defined models of monogenic as well as polygenic human disorders.

1. State of pluripotency: Mouse ES and iPS cells appear to represent a naive state of pluripotency corresponding to the inner cell mass (ICM), whereas human ES or iPS cells represent the “primed” state corresponding to mouse EpiSCs. A major question is whether the naive state exists in the human system. We have, using an unbiased screening approach, generated ES cells that display a transcriptome similar to the human cleavage embryo.

2. Disease modeling and iPS cells: A major incentive of the iPS cell system is to model human diseases in the Petri dish. However, a serious concern is whether a 2D in vitro system can faithfully model complex human diseases. We are, therefore, using a 3D organoid system to study human brain development and CNS disorders. Ultimately, human diseases need to be studied under in vivo conditions. To this end we are establishing various approaches to generate mouse – human chimeras.

3. Parkinson’s disease (PD): A major effort of the lab is devoted to study Parkinson’s disease (PD). We have generated isogenic pairs of iPS and ES cells that differ exclusively at the A53T or E46K mutation of the synuclein gene, both dominant point mutations that cause early onset of PD. However, the great majority of PD is polygenic with many loci that contribute to disease risk as identified in GWA studies. Most of these risk loci identified in GWA studies are localized to regulatory regions (as opposed to coding sequences), but these studies remain largely descriptive providing little or no mechanistic insight. Using CRISPR/Cas gene editing we have generated isogenic neurons that differ at specific GWAS SNPs in an effort to molecularly define the effect of risk alleles on down stream gene expression and cellular phenotype.
I. Cells for Therapeutic Development, Disease Modeling, & Drug Discovery.
Moderator: Robert Halliwell, University of the Pacific
8:45 Evaluating Human Stem Cell-derived Neurons for Neuropharmacology & Neurotoxicology Studies
Robert F. Halliwell
Professor, School of Pharmacy
University of the Pacific
  Important progress has been made identifying different sources of human stem cells but characterization of the somatic cells derived from them is still at an early stage. Our lab is investigating several sources of adult (somatic) stem, induced pluripotent stem (iPS) and embryonic stem (ES) cells to differentiate into functional human neurons. We are using single cell patch-clamp electrophysiology, immunocytochemistry and flow cytometry. This presentation will describe some of the neuropharmacological and neurophysiological properties of neurons derived from iPS and somatic stem cells. I will also describe some of our recent data addressing the value of these different human stem cells in vitro to predict developmental neurotoxicity that occurs in vivo.
9:10 Therapeutic Development and Disease Modeling Creation Utilizing Body-on-a-chip Systems Derived from Human Stem Cells
James Hickman

Professor, NanoScience Technology Center
University of Central Florida
Chief Scientist, Hesperos
  One of the primary limitations in drug discovery and toxicology research is the lack of good model systems between the single cell level and animal or human systems. This is especially true for neurodegenerative diseases such as ALS, Alzheimer’s, and spinal cord injury. In addition, with the banning of animals for toxicology testing in many industries body-on-a-chip systems to replace animals with human mimics is essential for product development and safety testing. Our research focus is on the establishment of functional in vitro systems to address this deficit where we seek to create organs and subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac and hepatocyte subsystems. The idea is to integrate microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. A complete cardiac system that reproduces the two main determinants of organ function, electrical activity and force, will be presented. A functional 2-organ system that comprises the components of the neuromuscular junction will also be described as well as its ability to evaluate therapeutics for diseased systems. A 4-organ system, where multi-organ toxicity is evaluated will also be discussed. All systems will be in a serum-free, defined medium and the 4-organ will be on a reconfigurable pumpless platform that lowers cost dramatically. The results of five workshops held at NIH to explore what is needed for validation and qualification of these systems will also be presented.
9:35 Are We Ready for Next Gen Approaches in Drug Discovery, Cell and Gene Therapy?
Devyn Smith
Head, Strategy for Pharmatherapeutics, Worldwide R&D
  Science is advancing at a rapid pace with new discoveries in gene editing, cell and gene based therapies occurring all the time. These new discoveries have the potential to impact our approaches to drug discovery as well as create new therapeutic approaches to treating disease. How much is hype vs reality?
10:00 Morning Networking Break
10:45 Genetically Engineered Stem Cells for Treating Spinal Cord Gliomas: A Neurobiology-based Approach
Yang (Ted) Teng

Associate Professor of Neurosurgery, Harvard University
Principal Investigator, The Brigham and Women's Hospital
Director, Division of SCI Research, VA Boston Healthcare System
  Current clinical regimen of surgery, chemotherapy and radiation shows very limited efficacy for spinal cord gliomas. To overcome this challenge, we, by C6 implantation of G55 tumor cells, established the first model of spinal cord glioma that manifested both somatomotosensory and autonomic dysfunctions. Human neural stem cells (hNSCs) engineered to express either cytosine deaminase (F3.CD) or CD-thymidine kinase (F3.CD-TK), kill cancer cells locally via tumor tracking and converting nontoxic 5-fluorocytosine (5-FC) and 5-FC+ganciclovir (GCV) into 5-fluorouracil (5-FU) and 5-FU+GCV-triphosphate, respectively, to trigger DNA fragmentation and apoptosis. Using in vitro assays we determined that F3.CD-TK treatment had stronger oncolytic effect relative to F3.CD. We next transplanted DiI-labeled F3.CD-TK, F3.CD, or F3.CD-TK debris close to C6 tumor mass 1 week post G55 injection (n=6/group), followed by 5-FC (500 mg/kg/5 ml/day) and GCV (25 mg/kg/1 ml/day) intraperitoneal administrations (x 5 days). Evaluation of autonomic parameters (i.e., respiratory function, blood pressure, and body temperature) and hindlimb locomotion was performed. All rats showed pathophysiological signs typical for cervical spinal glioma. Compared to controls, rats treated with F3.CD-TK plus 5-FC and GCV demonstrated significantly increased survival that was defined by retention of hindlimb stepping ability (P<0.05; ANOVA). The treatment also significantly mitigated respiratory and arterial blood pressure abnormalities. Analytical assays revealed that F3.CD-TK extensively infiltrated C6 tumor mass and after prodrug dosing, markedly impeded glioma growth, resulting in a topology of tumor microstructure that favored sparing of neural functions. Our data suggests that engineered hNSCs may be used under neurobiological principles to treat spinal cord gliomas.

1. Learn clinically relevant modeling of spinal cord gliomas;
2. Understand stem cell biology-based treatment of gliomas;
3. Be informed by a neurobiology-based approach to treating spinal cord tumors;
4. Discuss the importance of applying multimodal approaches in translational research;
5. Catch a tangible translational opportunity to developing a clinical therapy to treat high grade spinal cord gliomas
11:10 Total Quality Approach to Cell Therapy Production
Kevin Murray
Director, Sales & Marketing

  Total quality recognizes that for best cell potency, cells need full time optimization of all critical cell parameters (O2, CO2, RH & T). Total quality recognizes that all typical negative side effects of machines on cells (particles, heat, vibration, etc.) must be neutralized to make automation compatible with a cell optimized ecosystem and those machines must be protected from dust, aerosols, and corrosion. Total quality recognizes that each entire cell production line (all manual and automated steps) must be protected from microbial contamination by full time, absolute aseptic conditions. Total quality recognizes that all personnel must be fully protected from cells harboring virus, vectors, prions and other pathogens. Total quality recognizes that scaling up and out must be efficient. Total quality recognizes that cost efficiency is fundamental quality attribute, critical for commercial success. The Xvivo System is a comprehensive, modular, total quality platform for cell therapy production.
II. Advances in Adult & Pluripotent Stem Cell Research & Technology.
Moderator: Robert Halliwell, University of the Pacific
11:35 Human Neural Stem Cell for the Treatment of CNS Disorder
Ian Massey

President & Chief Executive Officer
Stem Cells Inc.

  Clinical Translation of Neural Stem Cell Transplantation: Emerging safety and preliminary efficacy with Human Central Nervous System Stem Cells, HuCNS-SC®

There are few effective therapies for diseases that impair normal function of the brain, spinal cord and eye. Human neural stem cell transplantation represents a potential new and innovative medical therapy which offers the prospect to treat a wide spectrum of human conditions. Human Central Nervous System Stem Cells (HuCNS-SC®) are a purified and expanded composition of adult human neural stem cells and the results of transplantation in disease specific animal models have demonstrated consistent biological properties and impact on the underlying pathophysiology. Preclinical studies have demonstrated durable cell engraftment and in vivo protection of host cells and/or improvements in functional deficits. These preclinical studies have provided critical proof-of-concept for approaches targeting neuroprotection and neural replacement in the human setting. Clinical development with HuCNS-SC transplantation has evolved to cover a spectrum of conditions and anatomic regions of the central nervous system. Each clinical study was supported by published preclinical research with relevant animal models and authorized by the U.S. FDA and other regulatory agencies. To date, clinical trial experience with HuCNS-SC has been acquired in four distinct human disorders; a fatal lysosomal storage disease, Neuronal Ceroid Lipofuscinoses (NCL); a fatal dysmyelination disorder, Pelizaeus-Merzbacher disease (PMD); traumatic spinal cord injury (SCI); and, advanced dry, age-related macular degeneration (AMD). The current clinical experience has demonstrated safety, feasibility, and tolerability of HuCNS-SC transplantation. In addition, the emerging preliminary efficacy data have revealed signs of biological activity that have supported advancing into multicenter Phase II proof-of-concept studies for SCI and AMD. The latest outcomes from these initial trials and a clinical summary covering all four indications will be presented.
12:00 Recent Findings from Academic Labs
Brock Reeve
Executive Director
Harvard Stem Cell Institute
  This talk will highlight some of the new work coming out of labs in the HSCI network and review options for bringing them to the clinic and the market.
12:25 Lunch Provided by GTCbio
1:30 World First Clinical Research Using iPS Cell and Its Path for Global Approval
Hardy T S Kagimoto
President & Chief Executive Officer
Healios K.K (RIKEN Venture)
  Dr. Kagimoto will be presenting on the unique challenges faced when trying to initiate clinical trials using iPSC for a wide variety of diseases including age related macular degeneration, congenital metabolic liver diseases and other pathological fields using Organ Bud technology. The presentation will focus on the corporate strategy necessary to bring cell based therapy as the de-facto-standard technology to overcome various regulatory hurdles at a global level.
III. Frontiers in Tissue Engineering.
Moderator: Keith Murphy, Organovo 
1:55 An Academic Model for Translation of Tissue Engineered Technology: How They Facilitate the Development of Therapies for Unmet Clinical Needs
Julie G. Allickson

Director, Translational Research
Wake Forest Institute for Regenerative Medicine
2:20 Advances in Accurate Modeling of Human Biology in Tissue Engineered Organ Systems
Keith Murphy
Chief Executive Officer
  The field of tissue engineering has evolved towards better and better approximations of native function over time. Recent advancements in 3D bioprinting using the proprietary NovoGen Bioprinting platform have yielded important results. This presentation will review the underlying mechanisms of 3D bioprinting and why they can lead to dramatic improvements in the replication of native function. Recent advances will be shown, along with data demonstrating significant overlap between native function and the function of tissues developed through 3D bioprinting. The applications of such tissues in both the development of novel medicines and in a clinical translational setting will also be described.
2:45 The Role of Expanded Multicellular Therapy in Repair and Regeneration of Ischemic Tissue
Ross Tubo
Chief Scentific Officer
  A variety of bone marrow derived cell therapies have been utilized to treat ischemic tissue damage and promote more balanced tissue repair under inflammatory conditions. Ixmyelocel-T, is an autologous, culture expanded, bone marrow-derived multicellular therapy, that contains MSCs and M2-like macrophages, as well as many of the CD45+ cells found in the bone marrow. MSC and M2-macrophages have been shown to exhibit properties useful for angiogenesis and modulation of tissue repair in response to ischemia. The contributions of MSC and M2-like macrophages to ischemic tissue repair will be discussed.
3:10 Afternoon Networking Break
IV. Immunotherapy - Revolution in Disease Treatments.
Moderator: Keith Murphy, Organovo 
3:40 Gene Modified Cell Therapies: Personalized Versus off the Shelf
Sicco Popma
Scientific Director, Gene Modified Cell Therapies
Janssen R&D
  Recent breakthroughs in gene editing technologies created opportunities to redirect immune cells to destroy cancer cells. Human T cells engineered to express chimeric antigen receptors (CAR) have shown to reduce tumors and thus demonstrated initial clinical proof of concept. These positive and promising clinical results ignited a race among biotechnology and pharmaceutical companies to commercialize gene modified cell therapies. This presentation will review and compare two different approaches to develop engineered cell therapies; personalized versus off-the shelf.
Short Oral Presentations.
Moderator: Keith Murphy, Organovo 
4:05 Expression of Proangiogenic Factors and Cutaneous Regeneration Potential of Hematopoietic Stem Cells (HSCs) as well as Mesenchymal Stem Cells in Skin Burn: A Comparative Study
Heba M Saad Eldien
Professor in Department of Histology & Cell Biology, Faculty of Medicine
Assiut University, Egypt
  In the last two decades, there has been a tremendous increase in the understanding of stem cell biology, including the field of cutaneous stem cells. Extensive stem cell research and potential clinical applications have provided new perspectives in the use of stem cells in the treatment of human skin disorders such as severe burns and wounds. However, questions regarding whether patients with a burn will accommodate stem cell therapy and what the benefit of stem cell therapy in burn wound healing may be still need to be answered. Stem cell research for skin regeneration following burns may have important clinical significance. In recent years there seems to be an unbounded interest adult stem cell: it includes include mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), concerning mesenchymal stem cells (MSCs). This is mainly attributed to their exciting characteristics including long-term ex vivo proliferation, multilineage potential and immunomodulatory properties. In this regard MSCs emerge as attractive candidates for various therapeutic applications. MSCs were originally isolated from the bone marrow (BM) and this population is still considered as the gold standard for MSC applications. Nevertheless the BM has several limitations. Thus, there is accumulating interest in identifying alternative sources for MSCs. To this end MSCs obtained from the adipose tissue have gained much attention over the last years since they can be easily isolated, without any ethical concerns. Human umbilical cord blood is a rich source of hemopoietic stem cells for clinical application and may be one of the largest sources of stem cells. Haematopoietic stem cell transplantation are capable of differentiating into skin. During this project we are trying to determine differential effect of Mesenchymal stem cells in comparison to CD34 in wound healing and Skin Regeneration MSC presence was established by quantitative and qualitative immunophenotyping of cells and using FITC attached to MSC phenotypic markers (CD271, CD73, CD90 and Haematopoietic antibodies (CD34 and CD45) were used as negative control. Isolation of CD34+ Cells from Cord Blood HLA-B2704 and HLADQB1-0201 genes were used to identify human MSCs to assess survival and propagation after transplantation Relative mRNA expression of Ang-1/2, CD31 and VEGF genes was analyzed using qRT-PCR. we summarize the main characteristics of stem cells in general and present the most recent knowledge in our understanding of these cells. We also address the difference in tissue regeneration potentials after using mesenchymal as well Haematopoietic stem cell transplantation in the aspect of stem cell biology.
4:20 Cardiac Atrial Appendage Stem Cells Engraft and Differentiate into Cardiomyocytes in Vivo: a New Tool for Cardiac Repair after MI
Yanick Fanton
Experimental Hematology – Physiology Group
Hasselt University, Belgium
  Recently, a new cardiac stem cell population was identified, called the cardiac atrial appendage stem cell (CASC). The safety and efficacy of autologous CASC transplantation in a minipig MI model was examined here together with assessment of possible tumorigenic potential for CASCs. CASCs were isolated from right atrial appendages of Göttingen minipigs based on a high aldehyde dehydrogenase activity and labeled with green fluorescent protein (GFP). After cell expansion, MI was induced by a 2h snare ligation of the left anterior descending coronary artery. Upon reperfusion, CASCs were trans-endocardially injected under NOGA guidance (MI-CASC, n=10). Non-transplanted pigs (MI, n=8) received sham treatment. Left ventricular (LV) function was assessed by 3D electromechanical mapping (EMM) and cardiac MRI. LV dilatation was observed in MI pigs at two months (2M), while in the MI-CASC group volumes remained stable. Global LV ejection fraction and regional wall thickening in border areas were better preserved in the MI-CASC compared to the MI animals. EMM showed decreased viability and wall motion in the LV for both groups POST-MI, whereas at 2M these parameters only improved in the MI-CASC. qPCR against the GFP gene revealed a high CASC cell retention of 19%. This was accompanied by cardiomyogenic differentiation in 98±1% of the transplanted CASCs, shown by a sarcomeric expression of cardiac troponin T and I. Second harmonic generation microscopy confirmed the formation of mature sarcomeres in CASC-derived cardiomyocytes. Moreover, functional integration was demonstrated by expression of the gap junction protein Cx43 between CASCs aligned with surviving cardiomyocytes, which was confirmed by the absence of cardiac arrhythmias. Possible tumorigenic properties of CASCs, isolated from human atrial appendages, were explored in immunocompromised mice. On million CASCs dissolved in Matrigel were injected in Foxn1nu mice. After 6 months none of the mice developed subcutaneous tumors, while all mice injected with a UM-SCC tumor cell line had to be sacrificed with large subcutaneous tumors after 2-3 weeks (n=10 for each group). This demonstrates that CASCS do not show any tumorigenic potential. In conclusion, CASCs preserve cardiac function by extensive engraftment and cardiomyogenic differentiation. Furthermore, this study provides a first proof of the safety of CASC therapy. CASCs thus seem very promising for myocardial repair after MI.
4:35 An Assessment of the Factors Affecting the Commercialization of Cellular Based Therapeutics

David Pettitt
University of Oxford
  Cellular based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics - offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular based therapeutics from “bench to bedside” remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell based therapy domain. Key electronic databases were searched and manuscripts subjected to pre-defined inclusion and exclusion criteria. Two independent reviewers examined the retrieved publications, and performed data extraction. 3374 unique publications were identified. 138 of these qualified for full assessment and subsequent data extraction. A number of key themes were identified, enabling examination of current challenges and opportunities facing cell therapy development, including manufacturing, regulatory, reimbursement, ethical and clinical adoption issues. In addition to an up-to-date analysis of the current landscape, we discuss a number of pragmatic solutions to facilitate future development and translation.
4:50 Day 1 Concludes
Day 1 Day 2
Day 2 - Tuesday, April 26, 2016
7:00 Registration & Continental Breakfast
Plenary Session: Stem Cell Research in the Diabetes Space..
Moderator: Kevin A. D'Amour, Viacyte
8:00 Biologic Replacement and Regenerative Medicine Strategies for Diabetes
Camillo Ricordi
Stacy Joy Goodman Professor of Surgery
Distinguished Professor of Medicine & Biomedical Engineering
University of Miami
  Strategies aimed at restoring beta cell mass generally fall under either Replacement (islet transplantation and stem cell differentiation), Reprogramming (from non-insulin-producing cells) or Regeneration (replication and induction from endogenous precursors/stem cells).

Objectives of cellular therapies and regenerative medicine strategies for treatment of DM are to reverse the disease condition and prevent the development of the severe chronic complications that can affect most organ systems in a large proportion of patients over time.

A multicenter Phase III trial of transplantation of adult pancreatic islet has been recently completed and is moving towards a Biological License Application (BLA) in the USA, while novel strategies to engineer an intra-abdominal mini-endocrine pancreas are currently tested in pilot clinical trials.

In T1DM, the additional challenge of the underlying autoimmune condition imposes consideration of strategies that would restore self-tolerance or abrogate the effects of autoimmunity, so that the immune system can no longer destroy the new insulin producing cells introduced either by regenerating, reprogramming or replacement (e.g., transplantation of pancreatic islets or stem cell derived insulin producing cells). Abrogation of autoimmunity or its effects could be achieved by either tolerance induction strategies or immune protection (e.g., engineered microenvironment or selective permeability physical barriers like those introduced by micro-, conformal- or nano-encapsulation). Any therapeutic strategy, to be considered must avoid side effects such as those associated with life-long immunosuppression, which now limits the indications of adult islet transplantation to the most severe cases of T1DM. There is a broad consensus on the idea that stem cells will eventually replace adult pancreatic islets in the future. However, the jury is still out regarding the candidate cell type/s and approach that will ultimately succeed. Current differentiation methods for adult stem cells span from signal-driven approaches, to genetic manipulation and even strategies of in-vivo maturation after systemic administration. The more suitable alternatives between replacement, reprogramming and regeneration strategies should be further developed in pre-clinical model systems and tested in pilot clinical trials, while carefully assessing safety, efficacy, cost-effectiveness and the relative potential for scale up, to offer a realistic therapeutic option for most patients affected by diabetes.
8:45 The Challenge of Stem Cells Research; Many Hurdles Remain
Bruno Doiron
Principal Investigator and Project Leader
University of Texas Health Science
Center at San Antonio
  The quest to replace insulin injection treatment has focused on two strategies: in vivo islet transplantation and in vitro nuclear reprogramming to produce differentiated beta cells. Ultimately, both strategies rely on encapsulation to implant islets or culture cells into the human body. The many hurdles involved with islet transplantation have yet to be overcome and, even if successful, the paucity of pancreatic donors limits this approach. An alternative approach has attempted to recapitulate the embryonic development of pancreatic beta cell in vitro using stem cells. However, the stem cell approach requires in vitro cell culture and still has to overcome the hurdle of encapsulation. Beyond the capsulation hurdle, there remains a lack of knowledge about the basic molecular/cellular events via which a completely undifferentiated cell can be transformed into a functioning tissues/organ which can be integrated into whole body homeostasis. Mark Twain said: “What gets us into trouble is not what we don’t know, it’s what we know for sure that just ain’t so.
9:15 Development of Stem-Cell Derived, Macroencapsulated Islet Replacement for Type 1 Diabetes
Kevin A. D'Amour
Vice President, Research
Chief Scientific Officer
  ViaCyte Inc. is a clinical stage company developing a stem cell-based islet replacement therapy for treatment of patients with diabetes. The therapy is a combination product comprised of pancreatic endoderm cells encapsulated within a retrievable delivery device, ENCAPTRA® Drug Delivery System. After implantation, encapsulated progenitor cells differentiate into glucose-responsive, insulin-secreting cells. The renewable starting material for cell product manufacturing is human embryonic stem cells that are directed to differentiate to the pancreatic endoderm cell product using scalable processes. The bio-stable delivery device is designed to fully contain cells and to protect cells from immune attack, with the goal of eliminating the need for immunosuppressant drugs.

Funding in part from California Institute for Regenerative Medicine; SP1-06513, DR1-01423, TR1-01215 and JDRF.
9:45 Combinatorial Development of Materials for Islet Transplantation
Daniel G. Anderson
Associate Professor
Massachusetts Institute of Technology
  The fibrotic reaction to implanted biomaterials is a fundamental challenge to the development of immuno-isolation devices. Here we describe our work developing new biomaterials and devices for the purposes of enabling islet transplantation. In particular we describe the development of a large library of synthetic hydrogel materials, and the characterization of their biocompatibility in vivo. Data will be presented on the nature of the immune response to these and conventional biomaterials. Several lead materials have been identified with significantly improved biocompatibility in rodents and primates. When formulated into microcapsules these materials enable functional, long-term islet transplantation in immune competent, diabetic rodents.
10:15 Morning Networking Break
Plenary Session: Regulatory Challenges in Cell Therapy.
Moderator: Alain Vertes, NxR Biotechnologies GmbHModerator:
10:45 Stem-Cell Based Product Characterization and Regulatory Science
Steven R. Bauer
Chief, Cellular & Tissue Therapies Branch
Center for Biologics Evaluation and Research (CBER)
Food and Drug Administration
  Stem cell based cellular therapies are being actively developed and hold great potential for treatment of a wide array of medical conditions. However, clinical use of stem cell-based products is novel and product characterization is challenging. In particular, identification of cell therapy product characteristics that will predict reliably the in vivo performance of cell-based therapies remains a largely unfulfilled challenge. In FDA terminology, lot release characteristics of identity, purity, and potency constitute critical quality attributes that are related to the ability of a given cell preparation to perform the desired biological function and result in the intended clinical effect. To date, optimal approaches to evaluation and selection of in-process or lot release tests that are predictive of effectiveness and safety often remain largely unknown for stem cell products. For stem-cell based clinical trial proposals submitted to FDA characterization of the cellular products often relies on the use of a small number of cell surface markers and some measures of cell product activity derived from current understanding of cells from the field of cell biology. The regulatory science question is whether or not the characteristics that are measured in product testing are indeed quality attributes and are predictive of clinical outcomes. This talk will provide a basic overview of the regulatory considerations for stem-cell based products and describe some of the regulatory science issues that arise during development such products. Then the talk will describe FDA’s MSC Consortium and our research efforts to develop strategies that will result in cell characterization methods able to predict quality, potency, and safety of MSCs, with implications for other types of stem cells and cell-based products in general.
11:30 Addressing Cell Characterization Measurement Challenges for Cell Therapy Products
Sheng Lin-Gibson
Deputy Chief
NIST, Federal Agency (National Institute of Standards and Technology)
  Cell therapy products (CTPs) are becoming commercially viable due to recent discoveries, technological advances, and increased investments. The industry must address key manufacturing challenges, including understanding and establishing Critical Quality Attributes (CQA) for candidate products. This talk will describe recent standardization efforts (including those within ISO) to define and assure CQA measurements. Defining CQAs (i.e., identity, quantity, purity/impurity, sterility, viability, stability, and biological activity or potency) for CTPs is challenging due to a lack of understanding in the mechanism of action (defining what is important to measure), dynamic and heterogeneous nature of the cell-based products (biological variability), and measurement variability. This effort includes the development of a framework for a common understanding of quality attributes for CTPs that is necessary to facilitate further discussions on how best to identify and address measurement needs and challenges. We show the importance of cell quantity measurements (i.e., cell counting methods) associated with clearly defined cell (sub)populations. We further provide the utility of this framework by breaking down the viability measurement and suggest strategies for achieving measurement assurance for cell assays.
11:55 Regulatory Science Initiative for Offering Stem Cell Therapies in Japan
Toshio Miyata
Executive Director
Health & Global Policy Institute
  With Japanese novel specialized approval system for regenerative medicine products,if the probable benefit and safety of treatments can be confirmed, adaptive licensing with condition is issued by the MHLW (Ministry of Health, Labor, and Welfare). Cardiac cell sheet for severe heart failure was first case of adaptive licensing in 2015. Dr. Masayo Takahashi conducted a first-in-human trial using iPS cells for age-related macular degeneration, a serious condition of the retina in 2014. As global competition in regenerative medicine intensifies there is clearly a need for harmonization of regulatory frameworks to support global development of regenerative projects like this. Japanese new structure for regenerative medicine promotes early patient access and provides economic impact on regenerative medicine industries.
12:20 Lunch on Your Own
1:45 Innovation Calls for Innovative Regulatory Mechanisms, Collaborations
Jiwen Zhang
Senior Director, Regulatory Affairs
Cell Therapy and Regenerative Medicine
GE Healthcare
  Stem cell technology and regenerative medicine have promised medical breakthroughs, and even cures, for patients in need. The advancement in this space is also driving new cutting edge sciences and technologies in clinical investigation, manufacturing capability, data analytics, and patient management. In order to realize the promises, and ensure patient’s access to safe and effective therapies, there is a need in global regulatory convergence and innovative regulatory mechanisms beyond the existing regulatory frameworks. With significant challenges in reducing the cost of manufacturing and ensuring quality products, regulatory mechanisms to help streamline process development and manufacturing changes are greatly desired. In addition, stake holder collaborations that are undertaken such as by Alliance for Regenerative Medicine, ILSI Health and Environmental Sciences Institute, are also critical to help advance the field.
Plenary Session: Translation to the Clinic: What's in the Pipeline?.
Moderator: Alain Vertes, NxR Biotechnologies GmbH
2:10 Receptor Targeted Encapsulated Stem Cells for Cancer: On the Road to Clinics
Khalid Shah
Associate Professor, Harvard Medical School
Director, Stem Cell Therapeutics & Imaging, Massachusetts General Hospital
  Multiple stem cell types have been shown to exhibit inherent tropism towards tumors. We have engineered different adult stem cell types to express therapeutic agents that simultaneously target multiple receptors on tumor cells and tumor associated endothelial cells and shown that these pathotropic delivery vehicles can effectively target sites of malignancy. Using our recently established invasive, recurrent and metastatic brain tumor models that mimic clinical settings, we show that that engineered human stem cells expressing novel bi-functional proteins and encapsulated in biocompatible gels target both the primary and the invasive tumor deposits and have profound anti-tumor effects. These studies demonstrate the strength of engineering different receptor targeted therapeutic stem cells and testing their efficacy in pre-clinical-therapeutic tumor models and form the basis for developing novel cell based therapies for cancer. This presentation considers the current status of stem cell-based treatments for cancer and provides a rationale for translating the most promising pre-clinical studies into the clinic.
2:35 Autologous Cell Therapies for TBI
Charles Cox Jr.
Director, Children’s Program in Regenerative Medicine
University of Texas Houston
  Our group has pursued the use of autologous bone marrow derived mononuclear cell therapy for severe traumatic brain injury (TBI) in pre-clinical, IND enabling, Phase 1 and Phase 2b clinical trials in both adults and children. The putative mechanism of action is modulation of the innate immune response to injury via microglial polarization/M1 microglial apoptosis resulting in volumetric preservation of tissue. In an attempt to mitigate against the issue of heterogeneity of initial injury in clinical trials, we have sought to use structural outcomes (volumetric preservation) as a primary outcome variable. Recent work has also led us to consider an early outcome (therapeutic intensity level or PILOT score) to be a potential primary endpoint due to the reproducible effect of blood brain barrier maintenance with cell therapy. Maintenance of the BBB reduces post-injury cerebral edema and elevations in intracranial pressure which are the primary therapeutic target in neurocritical care (Liao, et al., Peds Crit Care Med; 2015). The objectives of our presentation are: (1) Demonstrate pre-clinical POC data, (2) Review Phase 1 safety data that pointed to a structural treatment effect, (3) Update on the status of Phase 2 trials, (4) Discuss the rationale for novel endpoints in clinical trial design.
3:00 Afternoon Networking Break
3:30 Neural Progenitor Derived Exosomes
Steven Stice
D.W. Brooks Distinguished Professor, GRA Eminent Scholar
Director, Regenerative Bioscience Center
University of Georgia
   -  Exosome therapeutic mediated opportunities are expanding,
 - Human pluripotent stem cell derived neural stem cells are a unique source of exosomes. We are working specifically on neural stem cell derived exosomes.
 - ArunA has 12 years of human pluripotent stem cell derived neural stem cell high volume manufacturing experience and commercialized a human pluripotent stem cell derived product in 2006.
 - Neural cell derived exosomes can be isolated under uniform conditions
 - In vitro neural cell protection using neural cell derived exosomes will be presented
3:55 Engineering Genetic Cures: Genome Editing of Stem Cells
Edward Lanphier
President & Chief Executive Officer
Sangamo Biosciences
  Advances in human hematopoietic stem cell (hHSC) isolation, purification and re-engraftment, combined with the ability to engineer zinc finger DNA binding protein nucleases (ZFNs) that enable the targeted and permanent modification of any investigator chosen gene sequence, can create therapeutic outcomes capable of generating lifelong genetic cures. This approach is being applied in HIV (targeted disruption of the CCR5 gene in HSCs) and in beta-thalassemia and sickle cell disease (targeted disruption of BCL11A). However, the generality of the ZFN platform permits the targeted disruption and targeted gene correction of any therapeutically relevant gene, thus providing a platform for engineering genetic cures through genome editing of stem cells.
4:20 Engineering Stem Cell Therapies for Ocular Disease
Dennis Clegg

Professor, Molecular
Cellular & Developmental Biology
UCSB, Center for Stem Cell Biology & Engineering
  One promising option for the treatment of ocular disease is to develop cellular therapies using RPE and neural retinal cells derived from pluripotent stem cells. One strategy for treating dry age related macular degeneration is to implant differentiated, polarized monolayers of hESC-RPE or iPS-RPE on an extracellular matrix-based scaffold, whereby cells are provided with a supportive substrate to stimulate cell survival, differentiation and function. We describe recent efforts to develop tissue constructs to replace ocular tissue and translate them to the clinic.
4:45 Cell-delivered Gene Therapy for HIV
Geoff Symonds

Head of Scientific Affairs & Collaborations
  A cell-delivered gene therapy approach for HIV has been tested in animal models (humanized mouse and non-human primate) and is now being tested clinically. The approach involves introducing anti-HIV genes into hematopoietic stem cells and T cells to produce a population of protected blood cells. The hypothesis is that these gene-protected blood cells will have a therapeutic impact to decrease viral load and maintain CD4 T cell counts.
5:10 Late Stage MSC Product Development - A Key Time for Stem Cell Therapies
Dan Devine
Senior Vice President, Special Projects
  This presentation will provide a brief overview of late stage products being advanced by Mesoblast Limited, leveraging its leading position in the mesenchymal lineage cell therapy space. Indications include late stage heart failure, low back pain, graft versus host disease and the complications from diabetes. Lessons learned and ongoing challenges at Mesoblast, from its significant amount of experience in this space will be reviewed. Insights into cell therapy development will be discussed.
5:35 Networking Reception & Poster Session
Day 1 Day 2

stem-cell-research-regenerative-medicine Agenda