Stem Cells and Regenerative Medicine
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1 Q 0 Stem Cells and Regenerative Medicine Technologies and capabilities to add value to your company Differentiation HA-PPS for cartilage Parallel culture optimisation Stem Cell Therapies Fetal EPCs and MSCs STROCELL (ipsc-derived MSCs) Scaffolds Cell surface like coatings D porous scaffolds Technologies Commercial Application STROCELL (ipsc-derived MSCs) Ethical source of stem cells, scalable generic or patient specific MSC production Fetal Endothelial progenitor cells (EPCs) and Vascular disorders including ischemia and chronic wounds Hyaluronic acid pentosan polysulphate conjugate as a cartilage differentiation factor Hydrogel-based factor to stimulate repair of knee meniscus or spinal disk and for culturing assays Polymer materials that mimic key features of cell surfaces Surface coating or scaffold material to control cell differentiation, proliferation or adhesion Method for producing D porous tissue scaffolds Scaffolds for tissue regeneration or generating tissue-like in vitro screening materials High content parallel culture optimisation device Optimising cell differentiation and proliferation George Adamson - Director Commercial Engagement - Science Telephone + 0 Mobile g.adamson@uniquest.com.au Robert McLachlan - Associate Director, Commercial Engagement - Health Telephone + Mobile + r.mclachlan@uniquest.com.au
2 Technologies ipsc-derived MSCs Placental-derived stem cells for the treatment of vascular disorders Scalable generic or patient specific MSC production Proprietary closed system bioreactor expansion process Amenable to GMP production Ethical source of stem cells MSCs in clinical use are currently derived from patient or donor material. This leads to increased costs and variability in cell production, characteristics and quality. STROCELL has developed a simple one step small molecule-based process that allows the rapid and complete conversion of immortal human pluripotent stem cells into MSCs with superior proliferative, immunosuppressive and differentiation capacity. Cartilage repair Other MSC-related applications including vascular disorders and wound healing Status: STROCELL research has verified that ipsc-derived MSCs can be expanded in xeno-free media. Pure populations of fetal endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) from human term placenta Capable of forming new blood vessels in-vivo Improve leg circulation in models of ischemia Fetal EPC and MSC work synergistically A novel method of extracting multiple fetal endothelial progenitor cells (EPCs) and fetal mesenchymal stem cells (MSCs) from human term placenta. The isolated fetal EPCs are cells with self-renewal capacity capable of differentiating into blood vessels in-vivo and improving leg circulation in models of ischemia. Synergistic effects when Fetal EPCs and MSCs are combined in a wound healing animal model. Cell therapies for ischemia and wound healing Vascularisation of medical devices and implants Stem cell banking Status: Proof of concept data in animal models of ischemic disease and chronic wounds. 0 0 Cartilage differentiation factor Conjugate stimulates enhanced MSC differentiation to cartilage tissue compared to PPS alone Differentiation of MSCs does not continue beyond cartilage to become bone tissue Ready incorporation into hydrogel with or without MSCs to allow injectable delivery of a cell friendly matrix Hyaluronic acid has been conjugated to pentosan polysulphate via a straightforward linker using standard chemistry to yield an MPC differentiation factor. In vitro experiments have shown that an HA-PPS conjugate reduces proliferation of MSCs whilst enhancing chondrogenic differentiation to cartilage-like tissue without affecting cell viability. The conjugate can be incorporated in an HA-PEG hydrogel without compromising the hydrogel structure. Hydrogel-based factor to stimulate repair of knee meniscus or spinal disk Hydrogel-based factor/msc matrix to stimulate repair of knee meniscus or spinal disk Use to stimulate MSC differentiation for cell culturing assay applications 0 Q 0 P
3 TECHNOLOGY READINESS LEVEL () - Basic principles observed and reported - Technology concept &/or application formulated - Analytical & experimental critical function &/or characteristic proof of concept - Validation in lab environment - Validation in relevant environment - Prototype demonstration in relevant environment - Prototype demonstration in operational environment - Test demonstration - Routine use 0 - Product or outcome delivered to industry 0 0 Control/influence cell differentiation, proliferation or adhesion via use of functional material Present a cell with multiple different ligands or factors Materials can be used as a D scaffold or as a surface coating onto different materials Simple and robust method of preparation that controls nanostructuring features This technology involves mixing two matched polymers in a solvent in the correct ratios. Solvent removal results in a polymer surface with nanoscale protruding pillars with controllable nanoscale spacing. The pillars incorporate functional groups at their tips that can be conjugated to biofunctional species such as extracellular matrix molecules or differentiation factors. The spacing of these biological molecules attached to the pillars matches that of a cell surface. Polymer surface to control cell behaviour (differentiation, proliferation, adhesion) Material for D tissue scaffolds Coating for implanted medical devices (e.g. stents, electrodes) Coating for cellular bioassay system Scaffolds show good cell adhesion and can incorporate factors to promote differentiation or proliferation Controllable porosity allows ready diffusion to and from the evolving cellular tissue colonies Simple robust method of production that is anticipated to facilitate manufacturing regulatory approval Scaffolds can be prepared from a variety of polymer materials to allow optimal physical properties to be selected This technology involves a straightforward process of dissolving a polymer in an appropriate solvent, placing in a mould and reducing the temperature to set the mixture and then freeze drying to remove the solvent. This leaves a D porous polymer material (porosity can be controlled by polymer concentration). Factors to control differentiation or proliferation can be incorporated into the porous material. Scaffolds for tissue regeneration Preparing D tissues for in vitro screening Polymer materials that mimic key features of cell surfaces Method for producing D porous tissue scaffolds 0 Ability to test more culturing conditions and optimise desired outcome quickly Test up to 0 sets of conditions in parallel Provides ability to scan combinations of important determinants of cell line culturing including media components, paracrine signalling, immobilised agents, dynamic flow Uses small scale multi-well format to minimise use of precious materials The culture optimisation device consists of a multi-well plate layout. Factors can be immobilised within the wells to introduce variation in static components of culturing conditions. Each line of wells is connected by microfluidic channels which allow the influence of paracrine signalling an important aspect of culturing, and flow conditions to be evaluated. The microfluidic channel design also includes reservoirs for particular agents and mixers to control their combination thus providing an additional dimension of parameter variation. Optimising cell differentiation or proliferation Response of cell colonies or tissue samples to drug candidates High content parallel culture optimisation device Q 0 P
4 Capabilities Capabilities The University of Queensland World leading stem cell & regenerative medicine research The University of Queensland (UQ) has internationally renowned research capabilities in the stem cell & regenerative medicine space. This includes expertise in the differentiation and manipulation of various cell populations and functional polymer scaffolds. These research outcomes are underpinned by the ability analytical techniques to measure parameters, to build a fundamental understanding in the processes that influence the destiny of cells and the ways that these can be influenced to achieve a desired outcome. Specific area Stem cell differentiation Stem cell isolation Scaffolds & surfaces for tissues Analysis and understanding of cellular processes In-vitro disease models Example MSC differentiation to cartilage Isolation of EPCs and MSCs from placenta Polymer materials that mimic cell surfaces, readily prepared porous High content optimisation of cell culturing conditions ipsc-derived neuronal and cardiac disease models Q 0 P Q 0 P
5 Using engineering to solve problems in biology, particularly tissue engineering - Justin s work focuses on the application of engineering to problems in biology. In particular he applies a strong knowledge in engineering surfaces to the application of producing functional scaffolds and surface coatings that are optimised for tissue generation and cell culturing. Justin also has considerable activities in the development of microdevices which have been applied to optimisation of cell culturing conditions, early disease detection and analysis of cell migration. Justin has performed contract and sponsored research work for multinationals such as Mesoblast,, Rhodia, Unilever and Nestle International. Collaborates with leading universities around the world including MIT, Stanford (US), ETH, Max Planck Institute and UCL (Europe). Induced pluripotent stem cells, in vitro disease models, regenerative medicine Associate Professor Ernst Wolvetang is leading the derivation of footprint-free induced pluripotent stem cells (ipsc) in Australia, with a particular focus on neuronal and cardiac disease models. He is the inaugural director of the collaborative reprogramming network Cell Reprogramming Australia and organises the only annual Australian ipsc workshop. Associate Professor Wolvetang is a chief investigator at the Australian Research Council s Special Research Initiative in Stem Cell Science and Stem Cells Australia. Associate Professor Wolvetang serves on the editorial board of six stem cell journals; is listed inventor on four patents in stem cell research; and is a senior reprogramming scientist in Stem Cells Ltd. Fetal Mesenchymal Stem Cell Biology Professor Nicholas Fisk is Executive Dean of the Faculty of Health Sciences at the University of Queensland, and a maternal-fetal medicine specialist at the Royal Brisbane and Women's Hospital. He practices as a maternal-fetal medicine specialist / high risk obstetrician at the Royal Brisbane and Women's Hospital, and maintains a research group in UQCCR. His main research interests have been in human fetal mesenchymal stem cell biology and monochorionic multiple pregnancy, but also spanned non-invasive prenatal diagnosis, fetal nociception, caesarean section, preterm labour, obstetric ultrasound and drug development in obstetrics. A fetal-medicine subspecialist with an MBA and a PhD in fetal physiology, he has authored nearly 00 publications, and is a past President of the International Fetal Medicine and Surgery Society. Understanding important physiological and disease processes in skin biology Associate Professor Khosrotehrani is a clinician scientist interested in skin biology and regenerative medicine. He was recently appointed at the University of Queensland Centre for Clinical Research (UQCCR) and the newly established Translational Research Institute in Brisbane, Australia. Associate Professor Khosrotehrani obtained his MD from the Cochin-Port Royal School of Medicine at René Descartes University, Paris, France, specialized in Dermatology and a fellow of the Australasian College of Dermatologists. During his post-doctoral training at Tufts-New England Medical Center, Boston, USA, Associate Professor Khosrotehrani helped establish the contribution of pregnancy-associated stem cells to tissue repair by demonstrating their multipotent capacity with a specific potency towards the endothelial lineage. His research has broad applications in skin wound healing, regenerative medicine and cancer initiation and progression. Q 0 P Q 0 P
6 Capabilities Contact us Robert McLachlan Associate Director, Commercial Engagement - Health T: + M: + E: r.mclachlan@uniquest.com.au About The University of Queensland (UQ) The University of Queensland, Australia, is one of the world s premier teaching and research institutions. It is consistently ranked in the top 00 in the four leading independent global rankings. With more than,000 students and 00 staff, UQ s teaching is informed by research, and spans six faculties and eight research institutes. UQ also has more specialised fields of research well above world standard than any other Australian university, according to the 0 Excellence in Research for Australia (ERA) assessment. George Adamson Director, Commercial Engagement - Science T: + 0 M: E: g.adamson@uniquest.com.au About UniQuest UniQuest is UQ s main commercialisation company. Established in, UniQuest is one of the oldest, largest and most successful commercialisation groups in Australia. UniQuest manages an extensive intellectual property estate that has given rise to more than,000 industry partnerships, over 0 technologies licensed and more than 0 active start-up companies. UniQuest has raised more than $0 million to take UQ technologies to market, with UniQuest-licensed UQ innovations generating gross product sales of more than US$0 Contact UniQuest Level, GP South Building, Staff House Road The University of Queensland St Lucia QLD Australia 0 Telephone + 0 Q 0 P Disclaimer: The information contained in this document is for information purposes only and does not constitute, nor is it intended to constitute, the provision of financial product advice. Neither UniQuest Pty Ltd nor any of the other companies named in this document warrant that the information is accurate or complete. The information has been prepared on a reasonable endeavours basis. Investors must undertake their own due diligence and make their own assumptions on the prospects of any investment opportunity contained in this document.
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