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MSC2007 brought together more than 300 attendees from 27 countries and 127 institutions (MSC 2007 Program). This year's conference program will again bring you a diverse, global perspective on regenerative medicine and adult stem cell therapy.
MSC2009 • Program
Quick Links to daily schedule:
Monday • Tuesday • Wednesday
Program and Speakers:
Monday, August 17, 2009
12:00 p.m. Welcome to MSC 2009 by Stanton Gerson
12:15 p.m. Keynote speaker: Maria Siemionow (Cleveland Clinic) "Cellular Therapies Applied to Face Transplantation"
Face transplantation has become a clinical reality; however, as in the case of solid organ transplants, patients require lifelong immunosuppression to prevent graft rejection. New strategies for minimal immunosuppression or tolerance induction are needed in order to justify routine clinical application of composite tissue allografts (CTA) such as face transplants. We are currently testing different bone marrow and mesenchymal stem-cell-based therapies in experimental face transplant models as tolerance inducing strategies for potential future clinical applications.
1:15 p.m. Session I: Adult Multi-lineage Stem Cells
Chair: Michael Chopp (Henry Ford Hospital/Oakland University)
1:15 p.m. Arnold Caplan (CWRU) "All ADULT Mesenchymal Stem Cells are PERICYTES: The ORIGINAL Multi-Tasker"
Marrow derived adult Mesenchymal Stem Cells (MSCs) can be isolated and culture expanded. Although these cells are capable of differentiating into lineages that result in the fabrication of bone, cartilage, muscle, marrow stroma, tendon/ligament, fat and other connective tissues, MSCs have recently been shown to be intrinsically therapeutic. Such culture expanded adult/MSCs are immuno-modulatory especially in muting T-cells and, thus, allogeneic MSCs have been used to mute or cure graft-versus-host-disease and Crohn’s disease and are now being tested in certain autoimmune diseases. Furthermore, these allo-MSCs set-up a regenerative micro-environment which is anti-apoptotic, anti-scarring, mitotic for tissue intrinsic progenitors and angiogenic. These immuno and trophic activities result from the secretion of powerful bioactive molecules that, in combination, support localized regenerative event. The MSCs reside in every tissue of the body and function as perivascular cells (pericytes) until a focal injury occurs. At sites of injury the pericyte is released and functions as a MSC that provides molecular assistance in activities leading to tissue regeneration. Such assistance involves many tasks involving the immuno-protection and trophic activities provided by the MSCs.1:45 p.m. Bruno Peault (McGowan Institute) "The Vascular Wall as a Source of Stem Cells in Adult Organs"
Mesenchymal stem cells (MSC) have been extracted from multiple cultured fetal and adult organs but the identity, frequency and location, within native tissues, of these elusive stem cells have remained obscure. We now suggest that these multi-lineage progenitors originate in blood vessel walls. We have documented anatomic, molecular and developmental relationships between endothelial cells and myogenic cells within human skeletal muscle. Myoendothelial cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry, that regenerate myofibers in the immunodeficient mouse muscle ten times more effectively than customary myogenic progenitors and improve cardiac function after injection into the infarcted myocardium. Cultured myoendothelial cells proliferate, retain a normal karyotype, are not tumorigenic and survive better under oxidative stress than regular myogenic cells. Clonally derived myoendothelial cells differentiate into myogenic, osteogenic and chondrogenic cells in culture. Second, we have prospectively identified perivascular cells, principally pericytes, in multiple human organs on CD146, NG2, and PDGF-Rß expression and absence of hematopoietic, endothelial, and myogenic cell markers. Perivascular cells purified from skeletal muscle or nonmuscle tissues are myogenic in vivo and also improve cardiac anatomy and function after injection into the infarcted myocardium. Irrespective of their tissue origin, long-term cultured perivascular cells retain myogenicity; exhibit at the clonal level osteogenic, chondrogenic, and adipogenic potentials; express MSC markers; and migrate by chemotaxis. Expression of MSC markers was also detected at the surface of native perivascular cells. Thus, blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.2:15 Glauce Gaspar Gomes (Faculdade de Medicina de Ribeirão Preto, Brazil) “Proteomic Analysis of Subpopulations CD73+ Adult and Fetal Human Mesenchymal Stem Cells and Hepatic Pericytes”
2:30 Mihaela Crisan (Erasmus Stem Cell Institute for Regenerative Medicine, Netherlands) “Human Placenta is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells Throughout Development”
2:45 Ravenska Wagey (Stemcell Technologies, Inc.) “Expansion and Immunosuppressive Ability of Mesenchymal Progenitor Cells from Human Bone Marrow Cultured in a Novel Serum and Animal-Free Culture Medium”
3:00 – Break
3:15 p.m. – Session II: Pre-clinical Translational Models
Chair: Bruno Peault (McGowan Institute)
3:15 p.m. Michael Chopp (Henry Ford Hospital/Oakland University) "MSCs Promote Brain Remodeling"
MSCs enhance recovery of function when employed to treat many neurological diseases. In injured brain, such as stroke, MSCs stimulate and amplify the induction of angiogenesis, neurogenesis and synaptogenesis and white matter /axonal outgrowth. In this presentation, I will describe the coupling and interdependence among these restorative processes and how the astrocyte via the expression of vascular endothelial growth factor and the reduction of inhibitory glycoproteins orchestrates the MSC induced brain plasticity and recovery of function. In addition, a brief description of combination therapy, in which pharmacological agents prime the brain for the MSCs and thereby amplify the therapeutic effect of MSCs, will be presented.3:45 p.m. Robert Miller (Case Western Reserve University) "Cell-based Therapies for Demyelinating Diseases"
Demyelinating diseases such as Multiple Sclerosis are characterized by inflammation of the central nervous system that leads to a loss of myelin, oligodendrocyte death, axonal damage and functional deficits. Early in the disease there is extensive repair of damaged myelin and functional recovery. With continued disease activity, however the capacity for endogenous repair diminishes and functional deficits become irreversible. Current therapies are directed at reducing the inflammatory attack, however successful long term recovery will depend on promoting myelin repair. Cell based therapies are an attractive approach for the treatment of demyelinating diseases. Mesenchymal stem cells (MSCs have demonstrated immunomodulatory effects and our work suggests that they also have direct influences in neural cell development. In animal models of demyelinating disease treatment with MSCs results in long term functional benefits and enhanced myelin repair. Other stem cell populations including neural stem cells have been implicated in myelin repair and the relative merits of the different cell populations will be discussed.4:15 p.m. Jorge Siufi (University of São Paulo, Brazil) “Co-Transplantation of Bone Marrow Derived MSCs Modulates Cytokine Profile and Decreases the Incidence of GVHD in Mouse Experimental Model of Allogeneic HSCT”
4:30 p.m. Kathy Xu (Robarts Research Institute) “Schwann Cell Co-Culture Improves the Therapeutic Effect of Bone Marrow Stromal Cells on Recovery in Spinal Cord-Injured Mice”
4:45 p.m. Group discussion
5:00-6:00 p.m. – Short Talk Presentations
• Kenichi Tamama (Ohio State University) “Hypoxia Enhances Self-Renewal of Multipotential Stromal Cells Through HIF-Dependent and HIF-Independent Mechanisms”
• Shih-Chieh Hung (National Yang-Ming University) “Catechin Stimulates Osteogenesis by Enhancing PP2A Activity in Human Mesenchymal Stem Cells”
• Milla Lampinen (Finnish Red Cross) “Low Oxygen Conditions Accelerate Umbilical Cord Blood Derived Mesenchymal Stem Cell Growth With No Effect On Their Immunophenotype And Potency”
• Nelson Lizier (Instituto Butantan, Brazil) “Spontaneous Differentiation of Dental Pulp Stem Cells Towards Neural Cells”
• Hatim Hemeda (University Hospital of Essen) “Human Mesenchymal Stem Cells are Non-Hematopoietic ‘Immune-Like’ Cells that Respond to Inflammatory Signals”
• Feng Lin (Case Western Reserve University) “Complement Deficiency Impairs Immunomodulatory Capabilities of Mesenchymal Stem Cells”
• Michael Pelyak (Case Western Reserve University) “Accelerated Chondrocyte Extracellular Matrix Deposition through Dextran Sulfate Polystyrene, and Hyaluronic Acid”
• Mineo Iwata (Fred Hutchinson Cancer Research Center) “In Vivo Immunomodulation and Mobilization of Endothelial-like Cells Following Infusion of Marrow Stromal Cells (MSC)”
• Jack Milwid (MIT) “Mesenchymal Stem Cells Secreted Factors Up-Regulate IL-10 and Lead to the Reversal of Acute Renal Failure Independent of Transplantation”
• Lindolfo da Silva Meirelles (Universidade de Sao Paulo, Brazil) “Characterization of Cultured Human Adipose Tissue-Derived Pericytes”
• Ulrich Tigges (Burnham Institute for Medical Research) “Adventitial Progenitor Cells and Vasculogenesis”
6:00-9:00 p.m. – Poster Session with Heavy Hors D'oeuvres and Bar Service
7:00 a.m. – Breakfast
8:00 a.m. – Session III: Immunomodulation and Tolerance
Chair: Kenneth Cooke (University Hospitals Case Medical Center)
8:00 a.m. Alan Tyndall (University Basel) "Mesenchymal Stem Cells in the Treatment of Autoimmune Disease"
MSCs, otherwise known as multipotent mesenchymal stromal cells, are being examined for the treatment of autoimmune disease (AD) on the basis of their in vitro antiproliferative properties, efficacy in animal models, apparent low acute toxicity and the early positive anecdotal outcomes in human acute GVHD. Phase I/II clinical trials are underway in Crohn’s disease and multiple sclerosis (MS), systemic lupus erythematosus (SLE), and are being planned for systemic sclerosis (SSc), systemic vasculitis and other AD. Open issues include patient selection, disease stage and activity, MSC source and expansion and long-term safety. In particular, loss of tumour surveillance remains an open question. Multidisciplinary groups including the European League Against Rheumatism (EULAR) are collaborating to ensure maximal use of available resources to establish the place, if any, of MSC in the treatment of AD.8:30 a.m. Marc Dahlke (University of Regensburg) "Immunomodulatory abilities of MSCs"
Encouraging evidence suggests that the well-documented immunomodulatory abilities of mesenchymal stem cells might well be useful for immunomodulation therapy in the setting of solid organ transplantation. Since a variety of clinical studies making use of MSC for the treatment of blood, bone, kidney and heart disorders are underway, phase I and II studies applying MSC to patients after solid organ transplantation are just one step away. I will thoroughly review the preclinical evidence that suggests the usefulness of MSC therapy in solid organ transplant patients and suggest a possible study scenario for a phase I study applying MSC after allogeneic liver transplantation.9:00 a.m. Tracey Lodie (Genzyme) "A Look at Mesenchymal Stem Cells (MSCs) as Potential Cellular Immune Therapeutics to Treat Auto-immune Disease"
OBJECTIVE: The immunomodulatory properties of human and murine bone marrow –derived mesenchymal stem cells (MSCs) include suppression of T cell responses and reduction of key inflammatory mediators, such as IFN-gamma and TNF-alpha. We postulated that MSC mediated immune suppression may provide benefit in the treatment of spontaneous T cell-mediated autoimmune diseases, such as type 1 diabetes.
RESEARCH DESIGN AND METHODS: Allogeneic murine MSCs were administered intravenously in the non-obese diabetic (NOD) model of spontaneous diabetes, either prior to (preventative protocol) or at the time of disease onset (therapeutic protocol) in order to study the amelioration of disease.
RESULTS: Prophylactic delivery of allogeneic MSCs to pre-diabetic NOD mice delayed the onset of disease. Therapeutic treatment at the time of disease onset was effective in reversing disease, as measured by restoration of blood glucose levels to the normal range. These data suggest that MSCs are able to modulate an ongoing autoreactive immune response.
BENEFITS: MSCs can effectively alter an autoimmune response. MSCs can ameliorate ongoing diabetes. Impact of MSC Therapy on other auto-immune diseases.9:30 a.m. Tracey Bonfield (Case Western Reserve University) “Defining Mesenchymal Stem Cell Efficacy In Vivo in Asthma”
9:45 a.m. Paulette Conget (Universidad del Desarollo, Chile) “Immunomodulation Allows Beta-Pancreatic Islets Regeneration after Multipotent Mesenchymal Stromal Cells Endovenous Administration into Type 1 Diabetic Mice”
10:00 a.m. Jeffrey Auletta (Case Western Reserve University) “Human Bone Marrow-Derived Mesenchymal Stem Cells Modulate In Vivo T-cell Alloreactivity and Inflammation Following Murine Allogeneic Bone Marrow Transplantation”
10:15 a.m. Inkap Ko (Case Western Reserve University) “Targeting Mesenchymal Stem Cells to Treat Inflammatory Bowel Disease via Cell Surface Coating”
10:30 a.m. – Break
10:45 a.m. – Session IV: Trophic Pathways
Chair: Robert Deans (Athersys)
10:45 a.m. Darwin Prockop (Texas A&M) "Intravenous MSCs Form Microemboli in Lung and Improve Myocardial Infarcts in Mice by Activation to Express the Anti-Inflammatory Protein TSG-6"
Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (IV) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 X 106 hMSCs were IV infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr but < 1,000 cells appeared in 6 other tissues. The hMSCs in lung up-regulated expression of multiple genes with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, IV hMSCs but not hMSCs transduced with TSG-6 siRNA decreased inflammatory responses, reduced infarct size, and improved cardiac function. IV administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest improvements in animal models and patients after IV infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6. Supported in part by NIH grants P40 RR 17447 and P01 HL 075161.11:15 a.m. Anthony Ting (Athersys) "Adherent Stem Cells and Mechanisms of Trophic Benefit"
MultiStem, an adult bone-marrow derived stem cell, is currently being evaluated in clinical trials for the treatment of acute myocardial infarction and as an adjunct for hematopoietic stem cell transplantation for the treatment of hematological diseases. Additionally, MultiStem has been allowed by the FDA to be evaluated for the treatment of stroke. The therapeutic pathways underlying clinical benefit are primarily trophic, as limited cell persistence and maturation has been detected in pre-clinical models. Trophic pathways attributed to adherent stem cell use include neo-angiogenesis, cytoprotection, reduction in inflammatory cell extravasation, and host progenitor cell recruitment. The use of in vitro assays and cytokine array analysis demonstrate that MultiStem secrete a variety of factors involved in diverse cellular processes. These profiles are distinct when comparing MultiStem isolation and growth conditions to standard MSC cultures from identical donors. Furthermore, the repertoire of secreted factors can change in response to the cellular environment, when assayed by in vivo tissue microarrays. These analyses provide an important foundation for constructing accurate patient clinical endpoint assays.11:45 a.m. Christopher Weiss (University of Pittsburgh) “Modulating the Niche in Muscular Dystrophy Increases Host Regenerative Capacity”
12:00 p.m. Radhika Pochampally (Tulane Center for Gene Therapy) “Drosha but Not Dicer Regulates hMSCs Cell Cycle Progression Through a miRNA Independent Mechanism”
12:15 p.m. – Lunch Discussion with Stan Gerson “Experiences on the FDA Advisory Panel for Cell Tissue and Gene Therapy”
The FDA oversees new therapeutics in the area of cells, gene therapy, composite materials involving novel applications of cells and combination products through a section of the agency called the Center for Biologic Evaluation and Research [CBER]. As a member of the advisory committee, I have had the opportunity to observe the review process at public meetings and to note the complexity of both the process of serving on this governmental committee and of the interface between the need for confidentiality among sponsors seeking evaluation of new products and the interests of other commercial entities, the public advocacy groups, and the review panel. I will review the recent reviews of cord blood collections, orthopedic grafts, embryonic stem cells, and the prostate cancer cell vaccine developed by Dendrion. Some of the key issues that will be discussed include oversight by FDA of autologous blood human cells, tissues or cell/tissue products under section 361 of the PHS act – to prevent transmission of communicable disease – for homologous use, vs the broader oversight of the part of 21 CFR Part 1271. Management of reviews by different parts of the FDA for instance cancer cellular vaccine review under CBER rather than the Center for Oncologics, and the issues of safety for collection and storage of cord blood and primary or differentiated embryonic stem cells. The purpose of this presentation is to facilitate interactions with FDA and prepare those submitting BLA applications for the advisory board review process.
1:30 p.m. – Session V: Tissue Engineering Therapies
Chair: James Dennis (Case Western Reserve University)
1:30 p.m. Anthony Atala (Wake Forest University) "Regenerative Medicine: New Approaches to Healthcare"
Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the ageing population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Nuclear transfer and other sources of stem cells, such as those derived from amniotic fluid and the placenta, offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. We review recent advances that have occurred in regenerative medicine and describe applications of these new technologies that may offer novel therapies for patients with end-stage tissue and organ failure.2:00 p.m. Adam Katz (University Virginia) "Advancing Adipose-derived Therapies to the Clinic: Emerging Strategies and Commercial Considerations"
Adipose Tissue is a unique biological resource capable of providing vast amounts of matrix, bioactive factors, and a variety of cell types - including MSCs. Due to its unmatched abundance, expendability, ease of harvest, and mass donor appeal, adipose lends itself to a variety of therapeutic strategies. This presentation will highlight adipose-related clinical studies/applications that are imminent and/or currently in progress, with discussion of the regulatory, clinical and commercial considerations associated with a given strategy.2:30 p.m. Aart van Apledoorn (University of Twente, Netherlands) “Tissue Engineering Strategies for Diabetes Type I Treatment”
2:45 p.m. Irina Kerkis (Instituto Butantan, Brazil) “Corneal Reconstruction with Tissue-Engineered Cell Sheets Composed of Human Immature Dental Pulp Stem Cells”
3:00 p.m. Group discussion
3:15 p.m. – Break
3:30 p.m. – Session VI: Transplantation, Homing and Tissue Engraftment
Chair: Alan Tyndall (University Basel)
3:30 p.m. Robert Sackstein (Harvard University) "Glycosyltransferase-programmed stereosubstitution (GPS) of CD44: Using GPS to Steer MSC Trafficking"
The successful clinical implementation of stem cell-based regenerative therapeutics depends critically on the ability to deliver stem cells to sites where they are needed. CD44 is a transmembrane glycoprotein that is expressed at high levels on most stem/progenitor cells. A specialized glycoform of CD44 called “Hematopoietic Cell E-/L-selectin Ligand” (HCELL) is a potent E-selectin ligand. E-selectin is an endothelial molecule that is expressed constitutively on the luminal surface of bone marrow microvascular endothelium, and is also found on post-capillary venules at all sites of tissue injury. E-selectin receptor/ligand interactions mediate shear-resistant adhesive interactions between cells in blood flow and endothelium, the critical first step in recruitment of circulating cells to any target tissue. We have developed a platform technology called “Glycosyltransferase-Programmed Stereosubstitution” (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells. Ex vivo glycan engineering of CD44 via GPS licenses osteotropism of human MSC to the bone, where these cells differentiate into osteoblasts and produce human osteoid in a NOD/SCID xenotransplant model. GPS technology thus has profound implications in therapy of generalized bone diseases such as osteoporosis, and may also be exploited to enable other MSC-based applications in regenerative medicine, immunotherapeutics and cancer.4:00 p.m. Marc Penn (Cleveland Clinic Foundation) "Mechanisms of Stem Cell Based Cardiac Repair"
There are several lines of evidence that support the hypothesis that the temporal alignment of the SDF-1:CXCR4 axis improves myocardial repair and functional response. Our group has previously demonstrated that surviving cardiac myocytes in the infarct border zone begin to express CXCR4 36-48 h after myocardial infarction and that the level of expression increases through 96 h. Interestingly this up-regulation of cardiac myocyte CXCR4 expression occurs at a time of declining myocardial SDF-1 expression. That said, we and others have demonstrated that the sustained expression of SDF-1 following myocardial infarction leads to decreased cardiac myocyte death and improved cardiac function. Thus, the temporal alignment of SDF-1 and cardiac myocyte CXCR4 expression appears to lead to improved cardiac function. There are several indirectly lines of evidence that support the concept that stem cell therapy leads to improved tissue repair that will be discussed and will be discussed.4:30 p.m. Frank Marini (M.D. Anderson Cancer Center) "Mesenchymal Stem/Stromal Cell Migration to Tumors and Wounding Environments"
Mesenchymal stem/stromal cells (MSC) are a multipotent stem cell with the capacity to regenerate tissue at sites of injury. In the context of cancer, the tumor is synonymous with a wounded environment, secreting a number of inflammatory attractants, such as cytokines and chemokines. We and others have shown the propensity of MSC to migrate to the tumor microenvironment upon systemic injection (Studeny, Can Res2002, JNCI2004, Spaeth PLoS2009, Kidd, Stem Cells2009). Determining the inflammatory-specific migratory mechanisms of MSC will enhance the targeted delivery potential of MSC for wound intervention, and anti-tumor therapeutics or conversely can be used to block the interactions between MSC and tumors. In this regards we found that paracrine factors secreted by various adenocarcinoma cell lines including breast, ovarian, prostate, pancreatic and sarcomas elicit distinct gene expression signatures from the MSC. Based on real time RT PCR and ELISA data, we demonstrate that inflammatory mediators and their conjugate receptors on MSC respond to specific inflammatory factors released from the tumor microenvironment. Additionally, utilizing noninvasive, in vivo bioluminescent imaging we determined conditions under which MSC selectively migrate to sites of inflammation. Inflammatory insults investigated included cutaneous needle-sticks, surgical incision wounds, as well as xenogeneic and syngeneic tumors. We compared various routes of administration (IV, IP, Subcue), and observed that detection of systemically delivered MSC revealed persistent, specific co-localization with sites of tumor development and wound healing. This pattern of MSC tropism was consistent, independent of tumor type, immunocompetence, and route of MSC delivery. In this study we have identified conditions and migratory factors under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time.5:00 p.m. Jeffrey Karp (Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute) “Engineering of a Mesenchymal Stem Cell Homing Response”
5:15 p.m. David Wilson (Case Western Reserve University) “Whole Mouse Cryo-Imaging of Single Stem Cells in Cardiovascular Cell Therapy”
5:30 p.m. Group discussion
5:45 p.m. – Break
6:00 p.m. – Poster Session with Hors D'oeuvres and Bar Service
6:30 p.m. – Keynote Lecture: Linda Powers (Toucan Capital) "MSCs and Medical Tourism"
with Hors D'oeuvres and Bar Service
7:30 p.m. – Banquet Dinner
7:30 a.m. – Breakfast
8:00 a.m. – Session VII: Clinical Trials I
Chair: Kim Warren (Lonza)
8:00 a.m. Keynote Speaker: Katarina LeBlanc (Karolinska University) "Treatment of Graft versus Host Disease with MSC"
8:45 a.m. Randall Mills (Osiris) TBD
9:15 a.m. Vladimir Smirnov (National Cardiology Center, Russia) “Therapeutic Potential of Human Cord Blood Cells in Patients with Neurological and Psychiatric Disorders”
9:30 a.m. Shapour Shahgasempour (Shahid Beheshti University of Medical Sciences, Iran) “Autologous Bone Marrow-Derived Stem Cell Therapy in Patients with Burger’s Disease”
9:45 a.m. Group discussion
10:00 a.m. – Break
10:15 a.m. – Session VIII: Clinical Trials II
Chair: Stanton Gerson (Case Western Reserve University)
10:15 a.m. Kim Warren (Lonza) "Phased Process Development and Manufacturing for Clinical Trials"
This presentation will review the development steps needed to effectively move through clinical trials with a cellular product. The focus will be on scaling up the cell culture platform, efficient use of culture medium, and implementation of closed volume reduction at harvest. There will also be discussion on final containers and filling of cellular products.10:45 a.m. Eric Daniels (Cytori) "Adipose Derived Stem and Regenerative Cells for Acute Myocardial Infarction"
The pathway for a cell-based therapy product from idea to intervention is expected to be tortuous and expensive, with a roster of scientific, technical, and regulatory hurdles that must be overcome prior to use. Necessary checkpoints include characterization of the cell(s) of interest, demonstration of safety of delivering those cells and conclusive efficacy in preclinical models that approximate the clinical condition. Our focus is on the use of adipose tissue as an ideal tissue source for a stem and regenerative cell fraction that may have benefit in the setting of an acute myocardial infarction. Considerable basic and preclinical research around these cells has identified a potent angiogenic, anti-apoptotic and immunomodulatory role, which has been demonstrated in preclinical small and large animal models of acute ischemic injury. Along with the mechanistic evaluation, we have seen significant functional benefit. This body of evidence has led us to perform a double blinded, placebo controlled, multi-center feasibility trial to evaluate the safety and potential efficacy of adipose derived regenerative cells in patients post acute myocardial infarction. Enrollment in this study is complete, and we are awaiting all patients to reach the primary endpoint prior to unblinding and evaluation of functional parameters. From the standpoint of patient safety, all acute infusion related parameters have passed DSMB assessment. Taking a cell-based therapy from cell-lab to cath-lab deserves time and careful, broad investigation, including clinical testing in a controlled fashion.11:15 a.m. Greg Russotti (Celgene) "Comparison of Large-Scale Cell Culture Systems for the Commercial Manufacture of Mesenchymal Stem Cell Products"
One of the major challenges facing the cell therapy industry is the identification of suitable large-scale culture systems for commercial manufacturing. These systems will not only need to be scaleable and cost-effective, but must also be amenable to robust, reproducible processes that consistently yield a high quality product. There are currently many commercially-available culture systems from which to choose although some are not ideal and others are unproven for mesenchymal stem cell culture. Commercially-available culture systems, including various static systems, flow-through devices, and stirred vessel configurations, will be briefly reviewed and advantages and disadvantages of each discussed. Factors such as the largest feasible scale, medium requirements, complexity, scale-up challenges, monitoring and control capabilities, system impact on product quality, and capital and recurring costs will be considered. An emphasis will be placed on past experiences with these types of systems for the clinical and commercial production of established biotherapeutic products that also face the challenge of growing large quantities of anchorage-dependent mammalian cells. A thorough understanding of the existing alternatives along with evolving knowledge on the large-scale culture of mesenchymal stem cells will be essential in selecting the optimal system for one’s application and for the design of new and improved systems.11:45 a.m. Robert Mays (Athersys, Inc.) “MultiStem in Acute Stroke to Enhance Recovery Study (MASTERS): A Phase I, Dose Escalation, Placebo Controlled Clinical Trial Using MultiStem® for Treatment of Patients Suffering an Acute Ischemic Stroke”
12:00 p.m. William Prather (Pluristem Therapeutics, Inc.) “Update of Pluristem's Phase I Clinical Trial Using PLX-PAD in Critical Limb Ischemia”
12:15 p.m. Group discussion
1:00 p.m.– Closing Remarks: Arnold Caplan
Session IX: Commercializing MSC Therapy
Proudly sponsored by Invitrogen, part of Life Technologies, with boxed lunch provided to attendees in the session
1:30 p.m. - Dr. Mahendra Rao (Invitrogen, part of Life Technologies) Introduction
1:45 p.m. - Steven Bauer (FDA) "Regulatory update on MSC & Related Cell Types"
2:30 p.m. – Darwin Prockop "Running an MSC Bank"
3:15 p.m. – Break
3:30 p.m. – Lucas Chase / Eric Roos (Invitrogen, part of Life Technologies) "Xeno-free Scalable Culture of MSC"
4:15 p.m. – Robert Deans (Athersys) "Company Perspective on Cell Manufacture"
5:00 p.m. – Knut Niss (Pfizer) "Different Applications of MSCs – Screening / Therapeutic"
