Industry Update: Latest developments in stem cell research and regenerative medicine

Abstract

Regenerative MedicineVol. 6, No. 1 News & ViewsFree AccessIndustry Update: Latest developments in stem cell research and regenerative medicineDusko IlicDusko IlicEmbryonic Stem Cell Laboratories, Guy’s Assisted Conception Unit, Division of Women’s Health, King’s College London, UK. Search for more papers by this authorEmail the corresponding author at dusko.ilic@kcl.ac.ukPublished Online:22 Dec 2010https://doi.org/10.2217/rme.10.94AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Business Development▪ Collaborations, partnerships & alliancesCodevelopment agreement: Cell Cure & TevaBioTime, Inc., CA, USA (www.biotimeinc.com), its subsidiary Cell Cure Neurosciences Ltd. (www.cellcureneurosciences.com), and Hadasit Bio-Holdings Ltd. (www.hbl.co.il), both based in Israel, jointly announced that Cell Cure and Teva Pharmaceutical Industries Ltd., Israel (www.tevapharm.com) have entered into an exclusive license option agreement to develop and commercialize Cell Cure’s OpRegen™ product for the treatment of age-related macular degeneration. OpRegen is a proprietary formulation of human embryonic stem cell (hESC)-derived retinal pigment epithelial cells designed by Cell Cure. The BioTime, Teva and Hadasit Bio Holdings equity investments of US$7.1 million are funding ongoing development of OpRegen by Cell Cure. Equity investments were made simultaneously with this agreement. Office of the Chief Scientist of the Ministry of Industry, Trade and Labor of the State of Israel provided an additional nondilutive funding for the development of OpRegen. Subject to the terms of the agreement, if Teva exercises its option to obtain an exclusive license to OpRegen, Teva will have responsibility for funding clinical trials from that point on, obtaining regulatory approvals and marketing the product. Cell Cure will be entitled to receive milestone payments and royalties if certain development, regulatory and commercial milestones are achieved. A portion of the milestone payments and royalties received by Cell Cure would be shared with BioTime’s subsidiary, ES Cell International Pte Ltd., and with Hadasit Bio-Holdings’ affiliate, Hadasit Medical Research Services and Development Ltd., the technology transfer arm of the Hadassah Medical Organization, which have licensed certain patents and technology used in the development of OpRegen to Cell Cure that were invented by Professor Benjamin Reubinoff and Professor Eyal Banin.Codevelopment agreement: International Stem Cell & Insight Bioventures IndiaInternational Stem Cell Corporation, CA, USA (ISCO; www.internationalstemcell.com), a biopharmaceutical company that pioneered the creation of ‘human parthenogenetic stem cells’, and Insight Bioventures India Private Ltd (IBVI; www.insightbioventures.in) have agreed on financial and structural terms for establishment of an Indian affiliate of ISCO (ISCO India). This is an important milestone in ISCO and IBVI’s goal to facilitate development and commercialization of ISCO’s stem cell-derived corneal tissue, CytoCor™, and retinal cells, CytoRet™, for treatment of blindness and severe vision impairment, as well as cell systems for drug screening in India, and establish a manufacturing base for ISCO’s Lifeline Cell Technology® brand of cell culture media for commercialization throughout Asia. IBVI is an experienced biomedical business developer that facilitated the earliest cell therapy guidelines with the regulatory agencies in India and is well connected with Indian research and clinical centers, corporations and government. IBVI has now partnered with MARG Group (www.marggroup.com), one of India’s fastest-growing infrastructure developers with interest in ports, airports, power plants, commercial spaces, special export zones and other integrated infrastructures, to form Insight-MARG Biofund. The MARG Group is the lead facilitator of Biofund, the largest of its type in India so far.Codevelopment agreement: Nanotope & Smith & NephewNanotope, Inc., IL, USA (www.nanotope.com), Arrowhead Research Corporation’s, CA, USA (www.arrowheadresearch.com) portfolio company, has entered into an agreement with UK-headquartered, global medical devices company Smith & Nephew, Inc. (http://global.smith-nephew.com) to develop a cartilage regeneration product for human healthcare markets using a subset of its proprietary regenerative medicine technology. Under the agreement, Nanotope and Smith & Nephew will work together to optimize a cartilage regeneration product based on Nanotope’s proprietary platform. Smith & Nephew will conduct and assume costs associated with preclinical tests required to support clinical trials, purchase preclinical material from Nanotope and assume all clinical trial costs. Nanotope will potentially receive up to US$26.55 million in milestone payments plus sales royalties if all milestones are met. This represents Nanotope’s first commercial transaction and is in line with its strategy to leverage larger companies’ development and distribution capabilities within individual target markets.Nanotope is building a range of products to be injected into injured tissue, or in the case of wound healing, to be applied topically. Upon injection, the products form a substrate that actively directs surviving cells to regrow damaged tissue. The technical basis underlying this is a customizable chemical matrix, or gel, of nanofibers that provides 3D bioactive scaffolding in which cells and tissues may grow and differentiate. Two primary features of the gel are its customizable bioactivity and controlled gelation. These features result from engineered small individual molecules that self-assemble into nanofibers under physiological conditions.Collaboration agreement: AstraZeneca & University College LondonUK-based AstraZeneca and University College London Institute of Ophthalmology (www.ucl.ac.uk/ioo/index.php) have entered into a collaboration to develop regenerative medicines for diabetic retinopathy. Diabetic retinopathy is now the most common cause of vision impairment among people of working age in western society. The majority of patients with Type 1 diabetes will develop retinopathy and approximately 20–30% will become blind. Moreover, a large number of patients with Type 2 diabetes will develop retinopathy as their underlying disease progresses. With the global epidemic of Type 2 diabetes, this predicament is set to worsen as over 438 million people are projected to suffer from diabetes and its complications by 2030. Under the terms of the 3-year agreement, AstraZeneca and scientists at the University College London Institute of Ophthalmology will collaborate to identify new therapeutic tools that can modulate the regenerative capacity of stem cells.Collaboration agreement: CellCyte Genetics & Fred HutchinsonCellCyte Genetics Corporation, WA, USA (www.cellcyte.com) has signed a beta test collaboration agreement with the Fred Hutchinson Cancer Research Center, WA, USA (www.fhcrc.org) to evaluate the effectiveness of CellCyte’s CCG-E45 Culture Chamber product as a supplement or replacement to their current methods of culturing specific cell lines. CellCyte’s CCG-E45 Culture Chamber is a cell expansion device that allows the culture of cells at high density and under precisely controlled oxygenation, providing an alternative to standard cell culture methodologies. CellCyte is seeking additional collaborative relationships with other independent clinical research laboratories to apply this technology to a wide range of cell expansion applications.Collaboration agreement: Cellectis & Kyoto UniversityCellectis (www.cellectis.com), the French genome engineering company, and the Center for iPS Cells Research and Application of Kyoto University, Japan (www.cira.kyoto-u.ac.jp/e/index.html) have started a scientific collaboration to combine Cellectis’ genome engineering technologies with induced pluripotent stem (iPS) cell technology to improve the natural characteristics of iPS cells for use as cellular tools for drug development.Collaboration agreement: Geron & University of EdinburghGeron Corporation, CA, USA (www.geron.com) has entered into a worldwide, exclusive license agreement with the University of Edinburgh, UK (www.ed.ac.uk) covering technology that allows the efficient production of chondrocytes from human pluripotent stem cells. The license gives Geron exclusive rights to the technology for therapeutic applications, and will enhance Geron’s program to develop cell replacement therapies for orthopedic indications such as osteoarthritis. Financial terms of the license agreement were not disclosed. The technology was developed as part of research collaboration between Geron and the university. UK Stem Cell Foundation, with funding from Scottish Enterprise and the Medical Research Council, also supported the research. The studies showed that injection of hESC-derived chondrocytes into the damaged knee joint cartilage of immunocompetent rats produced well-integrated cartilage with full repair of the lesion for at least 9 months. Large animal models are now being used to test the cells in human-scale lesions to further assess cartilage integration, mechanical function and durability.Collaboration agreement: Geron & University of SuffolkGeron Corporation, CA, USA (www.geron.com) will team up with the University of Suffolk (www.ucs.ac.uk) to develop a treatment for joint disease and damaged cartilage. Preclinical studies have shown that an injection of chondrocytes, derived from hESCs, into damaged knee cartilage showed full lesion repair for at least 9 months. The project will be housed at the University of Suffolk’s biotechnology division and jointly funded by Geron and the university, with the university also providing equipment and facilities. Geron will finance the direct costs of the university’s development work.Licensing agreement: RTI & AthersysRTI Biologics Inc., FL, USA (www.rtix.com), a provider of orthopedic and other biologic implants, and Athersys Inc., OH, USA (www.athersys.com), a regenerative medicine and cell therapy research and development company, announced an agreement under which Athersys will provide RTI access to its Multipotent Adult Progenitor Cell technologies. Under the agreement, RTI has licensed Athersys’ technology to isolate and preserve cells from organ and tissue donors. This will enable RTI to develop and commercialize Multipotent Adult Progenitor Cell technology-based biologic implants exclusively for certain orthopedic applications. With this license, RTI expands its capabilities for accessing the fastest growing segment of the bone graft substitutes market, while Athersys extends the application of its robust stem cell technology platform to an important segment of the orthopedic market.Licensing agreement: ThermoGenesis & BioParadoxThermoGenesis Corp., CA, USA (www.thermogenesis.com), a supplier of innovative products and services that process and store adult stem cells, has entered into a license and distribution agreement for its Res-Q™ 60 BMC (Res-Q) System with BioParadox, Inc., a newly formed regenerative medicine company focusing on point-of-care cardiovascular therapies. Under the agreement, ThermoGenesis is granting BioParadox exclusive worldwide rights for use of the Res-Q technology to automate the preparation of platelet-rich plasma from peripheral blood, subject to BioParadox meeting certain milestones, including initiation and completion of clinical trials to support claims and maintain the rights. Res-Q is a point-of-care system designed for the preparation of cell concentrates. The device, in its current configuration, is used to process stem cells from bone marrow aspirate. With a minor modification, the device design also produces platelet-rich plasma from peripheral blood. ThermoGenesis has filed a 510(k) with the US FDA (www.fda.gov) seeking market clearance for use of the Res-Q System technology in the preparation of platelet-rich plasma from peripheral blood.Manufacturing agreement: Stemedica & AnC BioStemedica International, S.A., CA, USA (www.stemedica.com), a wholly-owned subsidiary of Stemedica Cell Technologies, Inc., announced the signing of an agreement to form a joint venture with AnC Bio, a Korean manufacturer of stem cell-based products (www.ancbio.com). The new venture, Stemedica AnC, will manufacture stem cells developed by Stemedica for the treatment of ischemic stroke and other degenerative disorders. The initial manufacturing capacity of this alliance will produce enough products to meet the company’s 5-year revenue projections, with an expansion capacity to manufacture multiple stem cell products to meet the anticipated long-term growth of the international market for stem cells. A board of directors representing both Stemedica and AnC Bio will oversee the joint venture. Planning for operations is expected to begin by the end of the year.AnC Bio Group is a Korean Corporation with three operating divisions: the cell therapy division, which includes a state-of-the-art cell culture current good manufacturing practice facility; the artificial organs division, which designs, manufactures and distributes artificial human organs such as kidney dialysis and artificial combined heart and lung machines; and the vaccine division, which develops, manufactures and distributes various kinds of cell culture-based vaccines including those for influenza, avian, Alzheimer’s and anthrax.Partnering agreement: Vitro & HemogenixVitro Diagnostics, Inc., dba Vitro Biopharma, CO, USA (www.vitrobiopharma.com) signed an amendment to its contract to jointly manufacture and distribute stem cell analysis tools with HemoGenix, Inc., CO, USA (www.hemogenix.com), a firm known for its HALO® analysis platform for stem cells. The previous agreement with HemoGenix led to the launch of LUMENESC-Hu™ and LumiSTEM™ assays for high-performance analysis of certain types of adult stem cells. The new amendment expands the original agreement to include development of stem cell culture media and high-performance toxicity assays to provide new cell-based tools for drug discovery and development. The partners also agreed to align their respective quality programs to assure consistency. An initial target of the expanded alliance is the development of a highly sensitive test for liver toxicity combining Vitro’s VITROGROW™ cell culture medium, human hepatocytes and the industry-adopted bioluminescent readout system that has been developed and perfected by HemoGenix. The resultant product is anticipated to provide state-of-the-art testing for detecting liver toxicity and drug-induced liver injury, which are major obstacles in the development of safe drugs and biologics. The partners plan immediate validation studies followed by a series of unique bioluminescent-based products incorporating highly sensitive hepatocellular viability measurements together with detection of indicative biomarkers to support safe and effective new drugs and biologics.Marketing agreement: Cytori & GE HealthcareCytori Therapeutics Inc., CA, USA (www.cytori.com) extended the term and modified the focus of a distribution deal with UK-based GE Healthcare (www.gehealthcare.com). The deal currently gives GE Healthcare rights to sell Cytori technology in select European research markets and the USA. In turn, Cytori has coexclusive sales rights in the research markets while retaining primary rights to sell into all clinical markets. The agreement has been extended through to the end of 2011. In Europe, GE Healthcare and Cytori now share coexclusive Celution™ System and StemSource® sales rights to hospitals for research and banking, and GE Healthcare will have nonexclusive rights for cosmetic and reconstructive surgery. The company’s StemSource products are used to extract, freeze and apply adult stem cells taken from fat tissue. In North America, GE Healthcare and Cytori share coexclusive StemSource sales rights for research and cell banking, and in Thailand, the companies share coexclusive Celution System and StemSource sales rights for research, and cosmetic and reconstructive surgery.Partnership agreement: Cellular Dynamics International & ACEACellular Dynamics International, WI, USA (www.cellulardynamics.com) announced partnership with ACEA Biosciences, CA, USA (www.aceabio.com) to bring early and accurate prediction of potential cardiotoxic side effects to the drug discovery process. The partnership combines Cellular Dynamics’ iPS cell-derived iCell™ Cardiomyocytes, with the xCELLigence RT-CA™ microplate biosensor platform. The xCELLigence System is developed by ACEA and Roche Applied Science, headquartered in Germany (www.roche-applied-science.com), and marketed by Roche. Cellular Dynamics has supplied purified human iCell Cardiomyocytes to ACEA for evaluation experiments, in which the xCELLigence RT-CA Cardio System was used to measure the effects of cardiac compounds with known electrophysiological and/or biochemical actions on the cells as well as drugs withdrawn from the market due to cardiac liability. The evaluation has been successfully completed, and the platform is in external beta testing at several pharmaceutical and academic institutions and will soon be made commercially available. iCell Cardiomyocytes, officially launched in December 2009, are the first commercial product developed from human iPS cells, and are gaining wide acceptance in industrial and academic research programs. iCell Cardiomyocytes beat spontaneously in vitro, and exhibit the electrophysiological and biochemical properties of normal human heart cells, thereby creating significant advances over current cardiac cell models. By providing a relevant human model, this cellular tool is designed to aid basic research and drug discovery by enabling more precise drug targeting and greater compound efficacy, as well as increased predictability of toxicity screens. As iCell Cardiomyocytes are an in vitro-based test system, they can be utilized early in the development pipeline to weed out ineffective and potentially toxic compounds prior to significant time and resource investment.Partnership agreement: Fate & BDFate Therapeutics, Inc., CA, USA (www.fatetherapeutics.com) has forged a collaboration and license agreement with BD, NJ, USA (www.bd.com), a global medical technology company, through its BD Biosciences segment, for the joint development and worldwide commercialization of iPS cell tools and technologies for drug discovery and development. Under the 3-year collaboration, Fate and BD will endeavor to codevelop certain stem cell products using Fate’s iPS cell technology platform, and BD will commercialize these stem cell products on a worldwide basis. The goal of the collaboration is to provide life science researchers and the pharmaceutical community with reliable access to advanced iPS cell tools and technologies for use in human disease research, drug discovery and development, and the manufacture of cell-based therapies.▪ Launching new products & servicesCook MedicalCook Medical, IN, USA (www.cookmedical.com), the world’s largest privately held manufacturer of medical devices, is providing plastic surgeons treating post-mastectomy patients access to breakthrough treatment options with Biodesign® Tissue Generation Matrix and Biodesign® Nipple Reconstruction Cylinder. Designed to signal the body to encourage tissue remodeling, the Biodesign grafts strike a critical balance of strength and flexibility that achieve aesthetically pleasing results. Both products leverage the proven Biodesign technology platform which has, to date, been used in more than 1 million patient treatments across nine procedural areas in 96 countries.Biodesign is a non-crosslinked, nondermis-based biologic graft that remodels into new patient tissue and is pliable yet long-lasting. Unlike many dermis-based grafts often used to reconstruct the breast, Biodesign is carefully processed to maintain its signaling and remodeling capability. Alternatively, acellular dermal matrices contain high amounts of elastin, which can remain in the patient’s body and stretch unpredictably. Biodesign avoids leaving behind meaningful amounts of elastin, providing lasting shape and support.The Biodesign Tissue Generation Matrix helps to rebuild the breast by signaling the body to generate new tissue. Engineered to maintain a precise balance of strength and flexibility, Biodesign maintains a natural feel before, during and after the tissue generation process. The material can be used across breast procedures including breast reconstruction, breast revision and mastopexy. Biodesign gives surgeons a way to restore a desirable aesthetic without leaving a permanent material behind.The Biodesign Nipple Reconstruction Cylinder is a first-of-its-kind product, providing a scaffold for re-establishing a nipple projection, historically viewed as a challenge for nipple reconstruction procedures. The nipple reconstruction cylinder gives a natural thickness and feel to projections giving physicians the ability to comprehensively complete the reconstruction process.FujifilmJapanese Fujifilm Corporation (www.fujifilm.com) introduced the ASTALIFT series of skincare products to the Chinese market in September 2010. The ASTALIFT series have earned high-user acclaim in Japan among women eager to maintain youthful skin. As part of its effort to expand the healthcare business, Fujifilm will initiate worldwide introduction of skincare products in which Fujifilm applies its proprietary technologies. Fujifilm’s ASTALIFT series is a comprehensive anti-aging skincare brand, developed by using its broad spectrum of core technologies accumulated over many years of research and development of photosensitive materials. These distinctive technologies include the findings of its collagen research, anti-oxidization technology and nanotechnology. Containing skin-replenishing collagen and astaxanthin, an increasingly popular skin-conditioning agent nearly 1000-times more powerful than coenzyme Q10, the products have received overwhelming support from women who seek to maintain the beauty of natural youthful skin since the launch in 2007.GE Healthcare & GeronUK-based GE Healthcare (www.gehealthcare.com) and Geron Corporation, CA, USA (www.geron.com) have launched a new human cellular assay product for use in drug discovery and toxicity screening, developed under a license and alliance agreement between the two companies. This commercially available product contains human cardiomyocytes and can be used to test the potential cardiac toxicity of candidate drug compounds in development. Assessing the effects of a drug candidate on heart function is an important and universal step in drug development. Cardiac side effects are a common reason for termination of late-stage clinical trials or for drugs to be withdrawn from the market. More accurate and earlier predictors of cardiac toxicities would contribute to reduced drug development costs and minimize patient exposure to potentially harmful compounds. The cardiomyocytes for toxicity screening available from GE Healthcare are derived from NIH-approved hESCs. This technology platform allows for the production of well-characterized master cell banks from which a continuous supply of human cardiomyocytes can be manufactured without the use of genetic modification. The GE Healthcare cell product has biochemical and electrophysiological properties analogous to normal cardiomyocytes present in the human body. Comparative studies conducted by ChanTest, OH, USA (www.chantest.com), an acknowledged leader in ion channel screening services, have demonstrated that these cardiomyocytes show a greater sensitivity to known ion channel blockers than current animal cell-based assays, enabling more reliable and earlier assessment of potential human toxicities in the development of pharmaceutical compounds. Further information on the cardiomyocyte product is available on the GE Healthcare website (www.gelifesciences.com/stemcells).International Stem Cell CorporationInternational Stem Cell Corporation, CA, USA (ISCO; www.internationalstemcell.com) announced that its wholly-owned subsidiary, Lifeline Skin Care, Inc., in partnership with an experienced drug licensed manufacturer of cosmetic products, successfully manufactured its first scaled-up lots of stem cell-based skin creams, confirming that these unique products can be made in larger batch quantities and continue to meet Lifeline’s high-quality standards. This marks an important milestone in proving that two new technologies, the derivation of human parthenogenetic stem cells, and the packaging and delivery of critical anti-aging ingredients (including those derived from stem cells), can be scaled-up to a level of production suitable to meet commercial levels of demand. Lifeline Skin Care’s product development scientists have combined human parthenogenetic stem cell technology with the latest discoveries in skin rejuvenation to create its unique day and night skin care creams. ISCO’s scientists were the first to intentionally create human parthenogenetic stem cells from unfertilized human eggs, thus avoiding the ethical concerns of harming a viable human embryo. ISCO’s therapeutic research team discovered that such cells had qualities that made them suitable for skin care products, thus leading to the formation of ISCO’s wholly-owned subsidiary, Lifeline Skin Care. Valuable assistance from ISCO’s other wholly-owned subsidiary, Lifeline Cell Technology, allowed the rapid transition and scale-up of a research-based discovery into a quality-controlled commercial product.ReproCELLHeadquartered in Yokohama, Japan, ReproCELL (www.reprocell.net) was known for manufacturing iPS cell-derived cardiomyocytes for drug toxicity testing and as the world’s first drug discovery support business provider founded on iPS cells. The prospective new offering of neuronal cells is the second line of services to be introduced by the company, and is a considerable expansion of their scope of business. ReproCELL will be the first in the world to offer iPS cell-derived neuronal cells and, more specifically, will provide dopaminergic neurons, motor neurons and cerebral nerves.Sigma-AldrichSigma Life Science, the innovative biological products and research services business of Sigma-Aldrich Corporation, MO, USA (www.sigmaaldrich.com), entered into the genetically modified cell market by announcing the global release of a pioneering range of engineered mammalian cell lines. This new product range combines Sigma’s proprietary CompoZr® zinc finger nuclease (ZFN) technology with the company’s extensive experience in gene silencing to offer innovative tools for drug discovery, compound screening and fundamental research applications. This new range of products includes immortalized cell lines for a broad spectrum of applications, each precisely engineered to help scientists answer specific biological questions. By exploiting the revolutionary genomic editing capabilities of ZFNs, Sigma’s scientists can rapidly manufacture stable cell lines with precise, well-characterized genetic manipulations. The program will use ZFNs to incorporate and develop cell lines with a variety of cellular markers expected to aid in compound screening studies and biochemical pathway analysis, as well as specific isogenic lines designed to advance colorectal and breast cancer research. In addition, Sigma offers a custom cell line engineering service, creating bespoke cell lines to perfectly match a researcher’s application. More information about Sigma Life Science’s cell line products is available at www.wherebiobegins.com/biocells.▪ AdvancementsAmericord RegistryAmericord Registry, NY, USA (www.americordregistry.com) announced its breakthrough placenta stem cell preservation process, the first of its kind, as a new and significantly more effective alternative to private cord blood stem cell banking. The new process, called Cord Plus, preserves up to ten-times more stem cells from the placenta than is found on average in a unit of cord blood, which contains only enough stem cells to treat a patient weighing less than 30 kg. As a result of this breakthrough, doctors may soon be able to cure substantially more people of sickle cell anemia, leukemia and other life-threatening blood disorders.AuxogynChoosing embryos for in vitro fertilization is fraught with uncertainty. The process has only a 35% success rate, and transferring more than one embryo to increase the odds of successful implantation increases a woman’s chances of having multiple births or requiring a selective abortion. By analyzing time-lapse videos of fertilized eggs as they develop, a team of researchers from the Stanford University School of Medicine, CA, USA (www.stanford.edu) has identified three specific milestones that eggs must reach in order to form a blastocyst, a critical stage [1]. The team created an algorithm for monitoring the embryos’ progress, and says this algorithm can predict which will develop to a blastocyst and which will die with 93% certainty. The technique could be used to enhance decision-making in the clinic, which currently relies on subjective evaluation of an embryo’s quality. Kleiner Perkins Caufield & Byers (www.kpcb.com), TPG Biotechnology (www.tpgbiotech.com) and Merck Serono Ventures (www.merckserono.com/en/index.html) funded and launched a spin-off company Auxogyn, CA, USA (www.auxogyn.com).Beta-ProBeta-Pro LLC, VA, USA (www.betaprolabs.com) has expanded its operations to accommodate increasing demands from pharmaceutical drug discovery and research institutes in the US$2 billion hepatocyte market. Beta-Pro’s new laboratory is designated as a good laboratory practice facility and is now fully operational. The company has moved its snap-frozen cell b