Innovation In Regenerative Medicine Research Articles

Immune-Epithelial Cross Talk in Regeneration and Repair.

The epithelial tissues that line our body, such as the skin and gut, have remarkable regenerative prowess and continually renew throughout our lifetimes. Owing to their barrier function, these tissues have also evolved sophisticated repair mechanisms to swiftly heal and limit the penetration of harmful agents following injury. Researchers now appreciate that epithelial regeneration and repair are not autonomous processes but rely on a dynamic cross talk with immunity. A wealth of clinical and experimental data point to the functional coupling of reparative and inflammatory responses as two sides of the same coin. Here we bring to the fore the immunological signals that underlie homeostatic epithelial regeneration and restitution following damage. We review our current understanding of how immune cells contribute to distinct phases of repair. When unchecked, immune-mediated repair programs are co-opted to fuel epithelial pathologies such as cancer, psoriasis, and inflammatory bowel diseases. Thus, understanding the reparative functions of immunity may advance therapeutic innovation in regenerative medicine and epithelial inflammatory diseases.

Prácticas disruptivas en la medicina regenerativa y la terapia celular: de la heteronormatividad de laboratorio a la emergencia de nuevas exclusiones bioeconómicas

Innovations in regenerative medicine and cell therapy have made possible multiple breakings in the laws and paradigms that determined the beginnings of 20th century biology. The destabilisation of categories and heteronormative dichotomies that demarcated this science made possible the irruption of studies that separated genetic research from sex. Even so, the current implementation of these techno-scientific developments produce other types of exclusion mechanisms we will analyse from a bio-economic point of view: from the reinforcement of the conditions of vulnerability of women donors, to the support of therapeutic promises that semiotically disconnect the contexts of uncertainty of these technologies or the implementation of a performative understanding of health in terms of individual consumption.

Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines.

Simple SummaryOsteoarthritis (OA) is the most common form of arthritis across the world. Most of the existing drugs for OA treat the symptoms of pain and inflammation. There are no drugs that can dure the disease. There are a number of new treatments for OA including cell therapy and gene therapy. This articles outlines the concept behind TissueGene-C, a new biological drug for OA. This new treatment includes cartilage cells mixed with a genetically modified cell line called GP2-293, which is effectively a “drug factory”, over-producing the growth factors that are important for cartilage regeneration and changing the environment inside joints. The mixture is injected into the affected knee joint. These cells are designed to be short-lived and cannot reproduce. Therefore, after they have done their job, they die and are cleared by immune cells. This is a new and modern approach to treating OA and TissueGene-C is the prototype cell therapy for OA. In the future, it is entirely possible to combine different clones of genetically engineered cells like GP2-293 that have been designed to over-produce a growth factor or biological drug with cells from the cartilage endplate of the intervertebral disc to treat degeneration in the spine.This review article focuses on the current state-of-the-art cellular and molecular biotechnology for the over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). Transfected protein packaging cell lines such as GP-293 cells may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage regeneration. However, when irradiated with gamma or x-rays, these cells lose their capacity for replication, which makes them safe for use as a live cell component of intra-articular injections. This innovation is already here, in the form of TissueGene-C, a new biological drug that consists of normal allogeneic primary chondrocytes combined with transduced GP2-293 cells that overexpress the growth factor transforming growth factor β1 (TGF-β1). TissueGene-C has revolutionized the concept of cell therapy, allowing drug companies to develop live cells as biological drug delivery systems for direct intra-articular injection of growth factors whose half-lives are in the order of minutes. Therefore, in this paper, we discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging eukaryotic cell lines are superior to prokaryotic bacterial expression systems and are likely to have a significant impact on the development of new humanized biological growth factor therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA, especially when injected directly into the joint.

Imagining the future of cell therapies: clinical trials, innovation and the intersection of clinical-academic and commercial visions

This paper examines the role of clinical trials in regenerative medicine innovation, exploring how trials have contributed to translational challenges in the field. Using data from an ethnographic study of UK cell therapy trials I interrogate the institutional framework for clinical trials and the identity-making of trialists. This analysis uncovers a disconnect between a commercially-aligned regulatory framework and a clinical-academic identity apparent in the majority of current trialling activity. These different pathways appear to represent two distinct sociotechnical imaginaries for cell therapies; one which reflects the assumptions of commercial innovation and prioritizes economic success, and another which embodies the cultural expectations of academia and emphasizes the importance of clinical care. These two imaginaries operate in synergy to some extent but there are significant tensions between them. How and to what extent these tensions are reconciled is likely to determine both the long-term success and the future shape of the field.

Three-dimensional printing biotechnology for the regeneration of the tooth and tooth-supporting tissues.

The tooth and its supporting tissues are organized with complex three-dimensional (3D) architecture, including the dental pulp with a blood supply and nerve tissues, complex multilayer periodontium, and highly aligned periodontal ligament (PDL). Mimicking such 3D complexity and the multicellular interactions naturally existing in dental structures represents great challenges in dental regeneration. Attempts to construct the complex system of the tooth and tooth-supporting apparatus (i.e., the PDL, alveolar bone, and cementum) have made certain progress owing to 3D printing biotechnology. Recent advances have enabled the 3D printing of biocompatible materials, seed cells, and supporting components into complex 3D functional living tissue. Furthermore, 3D bioprinting is driving major innovations in regenerative medicine, giving the field of regenerative dentistry a boost. The fabrication of scaffolds via 3D printing is already being performed extensively at the laboratory bench and in clinical trials; however, printing living cells and matrix materials together to produce tissue constructs by 3D bioprinting remains limited to the regeneration of dental pulp and the tooth germ. This review summarizes the application of scaffolds for cell seeding and biofabricated tissues via 3D printing and bioprinting, respectively, in the tooth and its supporting tissues. Additionally, the key advantages and prospects of 3D bioprinting in regenerative dentistry are highlighted, providing new ideas for dental regeneration.

AlcheMeat—how the future of animal production rests with biochemistry

Innovations in regenerative medicine, stem cell biology, tissue engineering, and biopharmaceutical production are responsible for saving countless lives and completely transforming healthcare. But what if this research could be applied to more than individual medical treatments? New applications within these fields could further address public safety concerns, global malnourishment, environmental issues, and animal abuse. In fact, these types of studies could lead to prevention of many of the diseases they initially set out to treat! Foci within these areas, such as telomerase expression, cell differentiation, induced pluripotency, three-dimensional tissue formation, recombinant protein production and CRISPR, are now being used for something entirely different — making meat.

Regenerative medicine in India: trends and challenges in innovation and regulation.

The government of India has heavily promoted research and development in regenerative medicine together with domestic innovation and business development initiatives. Together, these promise a revolution in healthcare and public empowerment in India. Several national and transnational linkages have emerged to develop innovative capacity, most prominently in stem cell and cord blood banking, as well as in gene therapy, tissue engineering, biomaterials and 3D printing. However, challenges remain of achieving regulatory oversight, viable outputs and equitable impacts. Governance of private cord blood banking, nanomaterials and 3D bioprinting requires more attention. A robust social contract is also needed in healthcare more generally, so that participation in research and innovation in regenerative medicine is backed up by treatments widely accessible to all.

Can harmonized regulation overcome intra-European differences? Insights from a European Phase III stem cell trial.

Harmonized regulation of research with human stem cells in Europe has shaped innovation in regenerative medicine. Findings from a Phase III academic clinical trial of an autologous cell procedure illustrate the obstacles that a multinational trial faces. A typology of the obstacles encountered, may help other teams embarking upon trials. The findings throw light on the situation of clinician-scientists in clinical innovation, as the expertise to run scientific trials is very complex. The innovation route of clinical translation takes insufficient account of the interdependencies between multiple social and cultural factors from outside the laboratory and the clinic. For ethical reasons, however, academic and business routes to stem cell treatments ought to be enabled by the regulators. Suggestions arise, how academics can prepare for trials, that academic research needs better institutional support and that new models of medical innovation may need to be developed for regenerative medicine.

Promissory identities: Sociotechnical representations & innovation in regenerative medicine

The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of ‘technology identity’ and ‘development space’ to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a ‘point-of-care’ cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways.

Looking to the future following 10 years of induced pluripotent stem cell technologies.

The development of induced pluripotent stem cells (iPSCs) has fundamentally changed our view on developmental cell-fate determination and led to a cascade of technological innovations in regenerative medicine. Here we provide an overview of the progress in the field over the past decade, as well as our perspective on future directions and clinical implications of iPSC technology.

Dental Applications of Natural-Origin Polymers in Hard and Soft Tissue Engineering.

Clinical advances in the treatment of dentoalveolar defects continue to evolve with the introduction of new innovations in regenerative medicine and tissue bioengineering. Recent developments in tissue engineering are aimed at safely and effectively regenerating a damaged or necrotic area by replenishing its cells and increasing surrounding gene expression. Various techniques have successfully given rise to porous scaffolds being used by clinicians to treat the defect and initiate the repair process. Tissue reconstruction using bioengineered scaffolds is advantageous over traditional autografting, since it prevents the instigation of pain and donor site morbidity while ultimately creating both the environment and machinery needed to induce cell proliferation, migration, and reattachment within the affected area. This review article aims to describe and review the available literature regarding the regenerative capacity of natural polymers used for the treatment of dentoalveolar defects. The repair mechanisms, advantages of protein and polysaccharide derivatives, and the potential of stem cell therapy are discussed.

Enamel: a unique self-assembling in mineral world

Enamel is a unique tissue in vertebrates, acellular, formed on a labile scaffolding matrix and hypermineralized. The ameloblasts are epithelial cells in charge of amelogenesis. They secrete a number of matrix proteins degraded by enzymes during enamel mineralization. This ordered cellular and extracellular events imply that any genetic or environmental perturbation will produce indelible and recognizable defects. The specificity of defects will indicate the affected cellular process. Thus, depending on the specificity of alterations, the teratogenic event can be retrospectively established. Advances in the field allow to use enamel defects as diagnostic tools for molecular disorders. The multifunctionality of enamel peptides is presently identified from their chemical roles in mineralization to cell signaling, constituting a source of concrete innovations in regenerative medicine.

The Netherlands advancing to the forefront of regenerative medicine.

The country, and especially Limburg, the most southern province, is making major leaps forward in the commercialization of regenerative medicine. Chemelot Campus, a major business park, is making a massive commitment with the creation of "Regeneration Street"; 50,000 m² of world leading research, development, manufacturing and innovation in regenerative medicine.

The Pharmacology of Regenerative Medicine

Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

Pursuing endogenous high-tech innovation in developing countries: A look at regenerative medicine innovation in Brazil, China and India

Few studies in developing countries have examined innovation in an emerging field such as regenerative medicine (RM). Here, we compare case studies of the RM sectors in Brazil, China and India to help understand RM innovation from a systemic perspective. Innovation in developing countries is usually described as a process of reverse engineering carried out by firms, but we argue that this description is not well suited to innovation in an emerging field such as RM. We show here that innovation in new emerging fields can occur in developing countries by diverse processes not yet discussed in the literature. We introduce the main types of actors in RM innovation, look at the interactions between users and producers, and discuss the advantages and challenges of innovating in RM that are faced by the emerging economies. We find that RM innovation in these countries is demand-driven and occurs under conditions unique to countries with lower-resources. We also find that firms play a smaller role in RM innovation at this stage, showing the importance of considering wider innovation actors in the study of novel innovation dynamics.

Recent Innovations in Medical and Surgical Retina.

To highlight recent innovations in the medical and surgical treatment of retinal disease. Retrospective literature review. The peer-reviewed, published (during 2012) English literature was searched using the Medline database. Articles deemed relevant were selected and highlighted. A number of important innovations in the treatment of retinal disease have occurred during the past year. We review developments in regenerative medicine (e.g., retinal prosthesis, optogenetics, cell-based therapy), diagnostics (e.g., swept source optical coherence tomography [OCT], intraoperative OCT, multimodal imaging), surgical innovations (e.g., chemical vitreolysis with ocriplasmin, 27-gauge vitrectomy), and pharmacological therapy of retinal vascular disease (e.g., use of ranibizumab and aflibercept in the treatment of macular edema associated with diabetic retinopathy and retinal vein occlusion). Many important innovations in regenerative medicine, diagnostic and surgical instrumentation, and pharmacological therapy for retinal vascular disease have occurred during the past year. In view of the number of agents in early phase clinical trials (e.g., treatments for dry age-related macular degeneration) as well as technologies under development (e.g., microrobots for vitreous surgery), this trend will continue.

Editor's Notes

Editor's Notes

The Role of Social Scientists in Accelerating Innovation in Regenerative Medicine

AbstractThe expertise of social scientists is vital in the field of regenerative medicine. By providing a comprehensive framework to include both technology and market conditions, as well as considering social, economic, and ethical values, they can inform policy decisions and influence the rate and direction of progress in new medical research. This paper deals with four potential conditions to which social science should pay special attention and assess: market conditions, technological opportunities, mechanisms of appropriability, and risk regulation of products and practices. The interplay of these factors must be understood as providing the right environment for this paradigm to progress. More empirical evidence is necessary to validate these factors in their international context, and this assigns a pivotal role to these experts.

Regenerative Medicine and New Labour life science policy: rhetorics of success, narratives of sustainability and survival

Advances in stem cell science and tissue engineering are being turned into applications and products through a novel medical paradigm known as regenerative medicine. This paper begins by examining the vulnerabilities and risks encountered by the regenerative medicine industry during a pivotal moment in its scientific infancy: the 2000s. Under the auspices of New Labour, British medical scientists and life science innovation firms associated with regenerative medicine, received demonstrative rhetorical pledges of support, aligned with the publication of a number of government initiated reports presaged by Bioscience 2015: Improving National Health, Increasing National Wealth. The Department of Health and the Department of Trade and Industry (and its successors) held industry consultations to determine the best means by which innovative bioscience cultures might be promoted and sustained in Britain. Bioscience 2015 encapsulates the first chapter of this sustainability narrative. By 2009, the tone of this storyline had changed to one of survivability. In the second part of the paper, we explore the ministerial interpretation of the ‘bioscience discussion cycle’ that embodies this narrative of expectation, using a computer-aided content analysis programme. Our analysis notes that the ministerial interpretation of these reports has continued to place key emphasis upon the distinctive and exceptional characteristics of the life science industries, such as their ability to perpetuate innovations in regenerative medicine and the optimism this portends – even though many of the economic expectations associated with this industry have remained unfulfilled.

Regenerative Medicine in Brazil: Small but Innovative

Although Brazil has received attention for conducting one of the world's largest stem cell clinical trials for heart disease, little has been published regarding Brazil's regenerative medicine (RM) sector. Here we present a comprehensive case study of RM in Brazil, including analysis of the current activity, the main motivations for engaging in RM and the remaining challenges to development in this field. Our case study is primarily based on semi-structured interviews with experts on RM in Brazil, including researchers, policymakers, clinicians, representatives of firms and regulators. Driven by domestic health needs and strategic government support, Brazil is producing innovative RM research, particularly for clinical research in cardiology, orthopedics, diabetes and neurology. We describe the main RM research currently taking place in Brazil, as well as some of the economic, regulatory and policy events that have created a favorable environment for RM development. Brazilian RM researchers need to overcome several formidable challenges to research: research funding is inconsistent, importation of materials is costly and slow, and weak linkages between universities, hospitals and industry impede translational research. Although Brazil's contribution to the RM sector is small, its niche emphasis on clinical applications may become of global importance, particularly if Brazil manages to address the challenges currently impinging on RM innovation.