Karl-Heinz Preisegger (VivoCell Biosolutions GmbH, Langenfeld, Germany):
Regenerative Medicine is certainly one of the youngest research fields. Nevertheless a lot of hope and emphasis is involved in the scientific work associated with this field and therefore it has gradually developed to a “global research project” that is probably one of the biggest of it´s kind ever with incredible progress every year.
Many of the pioneering innovations are achieved by cooperating teams of human and veterinary medical scientist.
VivoCell (formerly EccoCell Biotechnology) is a company inspired by the principle of translational medicine. In this regard the three main focuses of the company- research, clinical applications of stem cells in veterinary medicine and cord blood banking are an ideal combination. In order to enable as many patients as possible to receive a probably life saving stem cell transplantation VivoCell is currently setting up a public allogeneic cord blood bank in addition to the already established autologous private bank.
Over the years VivoCell has also been involved in several international as well as European research projects. New experience which we continuously gain through our research involvements is directly translated into innovations regarding cell preparation and expansion as well as therapies on the veterinary medical sector and the most recent and high quality standard of stem cell storage for later use in human medicine.
Therefore we are very excited about the idea of an interdisciplinary conference and are delighted to be a conference sponsor. We are convinced that the conference will be a good platform to develop new ideas, new projects and might lead to new and inspiring research cooperation between human and veterinary medical scientists as well as with and on the industrial sector.
Richard OC Oreffo (University of Southampton | School of Medicine | DOHaD, Southampton, UK):
Skeletal stem cell based strategies for bone regeneration – Bridging the Gap
Tissue engineering strategies have sought to repair skeletal defects resulting from trauma and disease with the application of cells, typically isolated from the patients themselves, in combination with porous biomaterials or scaffolds. Advances in our understanding of skeletal stem cells and their role in bone development and repair, offer the potential to open new frontiers in bone regeneration.
Our work is centered on isolation, expansion and translational studies of skeletal populations, including enriched skeletal stem cell populations for skeletal repair using biomimetic scaffolds together with judicious selection of osteotropic growth factors to generate appropriate skeletal tissue constructs. A key objective is translational studies to examine the efficacy of skeletal populations using impaction bone grafting as an exemplar and the exciting opportunities therein to improve the quality of life of many in an increasing ageing population.
Dieter Falkenhagen (Danube University Krems, Austria):
Our presentation entitled "The Hybrid MDS (Microspheres Based Detoxification System) – A future perspective for extracorporeal cell-therapy in sepsis and liver failure" describes a new hybrid technology based on the existing combined membrane and adsorbent system MDS which is characterized by the use of microparticles being smaller than 8 µm in suspension for the adsorption of sepsis – and liver failure related substances and encapsulated hepatocytes as well as monocytes applying a new encapsulation technology preparing cell-containing capsules smaller than 100 µm in diameter.
The new hybrid-technology opens new perspectives for extracorporeal cell therapy in combination with highly efficient and biocompatible adsorption therapy in sepsis and acute liver failure.
Damien Bates (Organogenesis Inc., Canton, MA, USA):
Organogenesis is a leading regenerative medicine company based in Canton, Massachusetts. In 1998, Organogenesis became the first company to gain US Food & Drug Administration (FDA) approval for a living cell therapy product called Apligraf®. Apligraf® comprises a complex extracellular matrix and human neonatal fibroblasts and keratinocytes. This product is indicated for the treatment of venous leg ulcers and diabetic foot ulcers which are amongst the most frequently occurring chronic wounds, affecting nearly two million people every year in the United States alone. Apligraf® is designed to modify and improve the body's natural response to injury in these hard to heal patients. Apligraf® improves the rate and quality of healing in wounds previously unresponsive to treatment. While many wound therapies are designed to passively manage the wound, Apligraf® plays a more active role in stimulating the skin and oral mucosa to regenerate itself by providing cells, extracellular matrix and secreted proteins (e.g. growth factors and cytokines) to the wound directly.
Robin A. Quirk (RegenTec Ltd, Nottingham, UK):
RegenTec Ltd – Injectable Scaffolds for Bone Repair Applications
RegenTec, a spin-out from The University of Nottingham, is involved in the design and manufacture of novel materials to support the creation of functional tissue structures. RegenTec’s scaffold delivery vehicles are based on a new concept involving a minimally-invasive injectable material that solidifies within the patient to form a porous template for tissue formation. The technology can be additionally employed as a drug and cell delivery system. The company is presently developing its injectable scaffold technology into a range of clinical products for use in bone repair. RegenTec’s Injectable Bone has received a Wellcome Trust Translation Award and was also the recipient of two prestigious awards (Best Orthopaedics Business Opportunity and Overall Winner for Orthopaedic Innovation) at the 2008 Medical Futures Awards ceremony. The presentation will focus on the potential clinical applications and benefits of injectable synthetic materials, and a summary of the technology transfer and commercial development of Injectable Bone.
Stephen F. Badylak (McGowan Institute for Regenerative Medicine, Pittsburg, PA, USA):
The use of biologic scaffolds composed of extracellular matrix (ECM), particularly xenogeneic extracellular matrix, has become commonplace in virtually every clinical application ranging from cardiovascular use to central nervous system applications. The source of these biologic scaffolds is widely varied and includes tissues such as the small intestine, the urinary bladder, the dermis, and pericardium. The species from which these tissues are harvested include the pig, cow, horse, and humans. These scaffolds, when prepared appropriately, support a constructive remodeling response and appear to circumvent the default mechanism of inflammation and scarring that typify mammalian wound healing. Interestingly, the immune response to these xenogeneic scaffolds has received relatively little attention. This presentation will focus upon the host response to xenogeneic ECM scaffold materials and the role of the innate and acquired immune response in the in situ remodeling of these scaffolds. Both preclinical studies and the results of human clinical studies will be presented.
Ian Wilmut (University of Edinburgh, MRC Centre for Regenerative Medicine, Edinburgh, UK):
Stem cells and drug discovery
The Centre for Regenerative Medicine Edinburgh focuses on the use of stem cells and their derivatives in studies of inherited diseases. New techniques make it possible to produce from patients who have an inherited disease cells that are equivalent to those early in their life before the symptoms of the disease became apparent. Comparison of these with healthy cells of the same type will reveal the causes of the disease. It may then be possible to use this new understanding to devise tests to identify the first drugs that are able to prevent those changes.
In addition, human cells in the laboratory may provide important new approaches to the safety testing of new drugs. Extensive tests are required for new drugs developed for treatment of any disease. Despite this effort many compounds are withdrawn late in the assessment process because they cause unacceptable side effects in some patients. Human cells derived from stem cells may offer opportunities to identify and eliminate compounds with unacceptable side effect at an earlier stage in the process. Liver, heart and nerve cells would be particularly useful for this purpose. Recent research at the Centre has improved procedures for differentiation hepatocyte-like cells from human embryo stem cells.
The network of European regulatory authorities co-ordinated by the EMEA allows for reliable marketing authorization procedures within 27 EU member states. The EMEA has established several working groups with expertise in the field of cell-based products. These groups provide guidance during the development procedure of regenerative cell-based products. In my opinion the conference is well conceived and the topics are broadly spread. The World Conference on Regenerative Medicine 2009 reflects the broad field of regenerative medicine and the variety of possible future therapy approaches and products.
Egbert Flory (Tissue Engineering & Somatic Cell Therapies, Paul-Ehrlich-Institut, GER):
How to put human cell-based medicinal products on the European market
Progress in the fields of medicine, biology and biotechnology has resulted in the development of promising cell-based medicinal products for the prevention and treatment of diseases or dysfunctions of the human body. Cell-based medicinal products can be divided in three categories such as cell-based vaccines, immunotherapeutics and cell/tissue regenerative products. Since 2004 about 220 clinical trials for Cell-based medicinal products are ongoing in the European Union (EU), targeting indications such as cancer, diabetes, cardio-vascular diseases and neurodegenerative disorders. The regulatory framework for cell-based medicinal products include the new regulations addressing all advanced therapy medicinal products. Marketing authorisation for Cell-based medicinal products follows the Centralised Procedure and is co-ordinated by the European Medicines Agency (EMEA) based in London.
The network of European regulatory authorities co-ordinated by the EMEA allows for reliable marketing authorization procedures within 27 EU member states. The EMEA has established several working groups with expertise in the field of cell-based products. These groups provide guidance during the development procedure of regenerative cell-based products. In my opinion the conference is well conceived and the topics are broadly spread. The World Conference on Regenerative Medicine 2009 reflects the broad field of regenerative medicine and the variety of possible future therapy approaches and products.
John A. Hunt (UK Centre for Tissue Engineering (UKCTE), University of Liverpool, UK):
Directing Human Adult Stem Cell Phenotype and Differentiation using Substrate Definition
The reproducible and robust application of stem cells both in vitro and in vivo as model assay systems or cell based medical therapies requires single cells and further populations of cells to be defined and controlled in terms of their phenotype and function. There are already many different approaches and techniques published in the scientific literature that demonstrate both embryonic and human adult stem cells are receptive to triggers to control their phenotype and function and can be directed down multiple lineages; this knowledge requires translation to provide systems that can provide highly defined populations of stem cells that can maintain their directed phenotype and function when placed into complex application specific environments without the dependence on soluble molecule supplementation. Defining the environment by precisely detailing the substrate chemistry of the material cells come into contact with using dip pen nanolithography® (DPN®) is demonstrating significant breakthroughs in providing large homogeneous populations of stem cells that can be taken forward as cells to tissues populations for in vitro assays or in vivo cell therapies.
Zami Aberman (CEO of Pluristem Therapeutics Inc, Haifa, Israel):
Pluristem Therapeutics Inc
Pluristem Therapeutics Inc. is a bio-therapeutics company dedicated to the commercialization of human-placenta derived cell-therapy products for the treatment of several severe degenerative, ischemic and autoimmune disorders. The Company is developing a pipeline of products, stored ready-to-use, that are a non-controversial source, and not from embryonic stem cells. US Food & Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application to initiate a Phase I clinical trial for the treatment of Critical Limb Ischemia (CLI), the end stage of peripheral artery disease (PAD), using Pluristem’s PLX-PAD. This will be the world’s first clinical trial using PLX-PAD, Pluristem’s placenta-derived stem cells that are expanded using the Company’s proprietary 3D PluriX™ technology. In addition, Pluristem has filed an Investigational Medicinal Product Dossier (IMPD) with the Paul Ehrlich Institute (PEI) in Germany.
Pluristem is delighted to be a sponsor of the World Conference of Regenerative Medicine. The Congress offers a unique European forum in which the newest breakthroughs in topics from stem-cells to biomaterials can be discussed with representatives from academia, industry, regulatory authorities and venture capital firms.
Arnold R. Kriegstein (University of California | Dept. of Neurology, San Francisco, CA, USA):
The Dynamics of Neural Stem and Progenitor Cells in Cortical Development and Therapeutics
Recent work has identified the neural stem cells in the embryonic and adult brain and is unraveling the mechanisms by which new nerve cells are created and delivered to their correct locations. Radial glial cells, present only in the embryonic and fetal brain and long thought to simply guide embryonic nerve cells during migration, have now been identified as neuronal stem cells in the developing brain. Radial glia largely produce neurons through intermediate progenitor cells that undergo symmetric modes of cell division in the subventricular zones of the embryonic brain. These symmetric divisions increase the numbers of cells that are of a given type, for example cortical inhibitory interneurons. This two-step process of neurogenesis suggests new mechanisms for the generation of cell diversity and cell number in the developing cortex. Additionally, production of neurons through intermediate progenitor cells suggests strategies for generating large numbers of specific neurons for cell-based therapies.
Alexander Meissner (Harvard University | Dept. Stem Cell and Regenerative Biology, Cambridge, MA, USA):
Epigenomics and reprogramming
Our ability to characterize mammalian epigenomes has been markedly enhanced by technological developments in recent years. In particular, the introduction of ultra high-throughput sequencing has improved the precision, comprehensiveness and throughput of techniques for mapping chromatin and DNA methylation. I will focus on these new applications and their promise for high resolution interrogation of mammalian epigenomes in development and disease.
Jeff W.M. Bulte (Johns Hopkins University School of Medicine | Institute for Cell Engineering, Baltimore, MD, USA):
Cellular Magnetic Resonance Imaging in Regenerative Medicine
The clinical use of novel experimental stem cell therapies in regenerative medicine requires methods that monitor the biodistribution of cells in a non-invasive manner. Magnetic resonance (MR) imaging is used clinically and provides excellent soft tissue contrast. The most sensitive MR labels to date are superparamagnetic iron oxide nanoparticles or SPIOs. SPIOs are clinically approved diagnostic agents and entered the clinic for use in cell tracking in 2004. The first phase I clinical trial demonstrated the feasibility and safety of dendritic cell cancer vaccine MRI tracking in melanoma patients. As of today, 4 clinical trials on MRI cell tracking using SPIOs have been published, incl. neural stem cells in the brain of trauma patients, bone marrow stem cells in spinal cord injury, and pancreatic islet cells for type I diabetes.
We are applying MRI cell tracking to different disease models including multiple sclerosis, myelin diseases, stroke, and diabetes. and have recently developed novel semi-permeable alginate capsules that simultaneously offer immunoprotection of transplanted (stem) cells and that are visible with MRI, CT, and X-ray imaging; further work in large animal models will be highlighted.
Giulio Cossu (Stem Cell Research Institute, Milan, Italy):
Clinical Trials planned for Cell Therapy of Muscular Dystrophy
Mesoangioblasts are recently characterized progenitor cells, associated with the vasculature and able to differentiate into skeletal muscle. Normal mesoangioblasts given to dogs suffering from dystropy resulted in a partial clinical recovery of muscle function. (Sampaolesi et al. Nature 444, 574, 2006). These results show the efficacy of cell therapy in a large, immuno-competent animal and set the rationale for a future clinical trial. Based on these results a first clinical trial in humans with donor mesoangioblasts is planned for the near future.
Jeffrey Karp (Havard-MIT Division of Health Sciences and Technology, Camridge, MA, USA):
Gecko Inspired Biomedical Adhesives
Biomimicry (from bios, meaning life, and mimesis, meaning to imitate) in biomedical engineering involves innovation through imitating existing designs in nature. Dr. Karp will describe biomimetic approaches employed to create biomedical adhesives (inspired by the geckos climbing ability). Geckos attach to smooth vertical surfaces and support their weight with a single toe. The mechanism of this biological phenomenon was recently elucidated; nearly two millennia after Aristotle first reported it. Each gecko foot is covered with as many as 500,000 fine hairs, each tipped with hundreds of projections known as spatulae.
Since each spatula’s length is on the order of 200-500 nm, it is possible to mimic these adhesive regions using nano/microscale approaches.