Genomic engineering has enormous potential along basic research, drug discovery and cell therapeutics. Many existing methods for targeted gene knockout mutagenesis or integration rely on homologous recombination. The low rate of spontaneous recombination in nearly all mammalian cell types, as well as the scale of screening, effort and time required to isolate the targeted events during genome modification, have hindered progress in this field. The present review has the objective to present latest improvements of technology to develop genetic modification to a clinical grade level so it can be used in human therapy. Keywords: Genomic editing, naive pluripotent stem, patient-specific, pluripotent, stem cell/genetic therapy.
Use of animal products to culture human stem cells poses risk of pathogens and other contaminations which may render stem cells therapeutically unsuitable. Hence, it is necessary to meet the standards of good manufacturing practices, clinical-grade like and xeno-free conditions. The protocol for culturing clinical grade stem cells needs to be modified so that maximum utilization can be done for stem cell therapies. Modifications can be in the media compositions, additional growth factors, small molecule compounds, and gene manipulations of the required transcription factors or the platform in which stem cells can grow. After the clinical grade standards are met it needs the approval of FDA for use as transplantation therapies. This review provides various methods and inventions for culturing clinical grade stem cells which have been patented. Keywords: Clinical grade, cytokines, embryonic stem cells, growth factors, induced pluripotent stem cells, matrix, mesenchymal stem cells, stem cells, xeno-free.
Stem cells have the ability to self-replicate in vitro indefinitely under adequate conditions and provided that pluripotent signals are triggered exogenously. Moreover, they are able to differentiate into virtually all human cell types. This vast potential makes stem cells a powerful tool to be used in regenerative medicine and different therapeutic strategies as well as in clinical and basic research, contributing to the generation of novel therapeutic avenues to treat innumerable pathological disorders that today have no known cure. Despite increased disclosures at a high speed pace in terms of benefits, applicability and relevance of stem cell based therapies; more studies in humans are needed to advance in the establishment of safe and effective cell-based treatments. In this review we compile an overview of the latest reports and patents on stem cell accomplishments for the treatment of diseases and injuries from Patent databases as The European Patent Office, WIPO, Fresh patents and Freepatents online, as well as Pubmed references, regarding stem cell therapy. Nevertheless, the vast majority of these promising results have been established in animal models, suggesting that stem cells research must go on prior to transferring therapeutic protocols to the human being although it has much to offer to improve life quality and eliminate disability. Keywords: Cell therapies, engraftment, IPSCs, microvesicles delivered from embryonic stem cells, proliferation stimulating antibodies, stem cell size.
Gene therapy strategies have become involved in methods for the treatment of inherited or acquired diseases with the aim to correct the faulty genetic code or to modify gene expression. In order to develop safe and effective therapeutic methods for applying in humans, different nucleic acids, termed as vectors, have been engineered, as therapeutic molecules in addition to classical drugs. In this review we included an overview of recent research and patents on therapeutic nucleic acids, designed for use on safe and effective gene therapy protocols for the treatment of diseases, whose results have been obtained in animal models, and which suggests that the use of nucleic acids as therapeutics molecules holds great promise for the future of disease control or cure. Keywords: AAT deficiency, cancer, childhood cerebral adrenoleukodystrophy, gene therapy, haemophilia, inherited retinal degenerations, non-viral vector, nucleic acids, rheumatoid arthritis, viral vector.
Stem cells possess a great potential of differentiating into various types of cells. They are capable of sustaining their stemness or getting converted into cells having a more specialized function in the body. The obstacles that pose as a barrier to the therapeutic and clinical applications of stem cells are the difficulty in deriving and controlling the fate of these stem cells. With the advancement of science and technology and with better knowledge, scientists have come up with the method of reprogramming for the generation of iPSCs. Reprogramming refers to converting a differentiated cell into its embryonic state, capable of re-differentiating into other cell types. These iPSCs phenotypically as well as morphologically resemble ESCs. Induced pluripotent stem cells are of great advantage for studying the pathogenesis of disease and drug discovery. Understanding the regulation of stem cells is of great importance so as to generate a controlled stem cell fate and function. A safe, more efficient and a cost-effective approach to this is the use of small molecules for reprogramming. Small molecules are easier to handle and provide a good tool for use in in vitro and in vivo studies for the development of therapeutics. Recently, fine-tuning of various combinations and concentrations of the small molecules helps provide control over the regulation of iPSCs and the reprogramming outcomes. In this article, we review patents and discuss the recent development with respect to the use of small molecules, their control over the cell fate, the effect on regulation of the reprogramming factors and the efficiency of reprogramming. Keywords: Cell fate, induced pluripotent stem cells (iPSCs), reprogramming, reprogramming efficiency, small molecules, stem cells.
Multipotent and pluripotent Stem cells are highly clonogenic populations of cells considered the utmost promise in the field of regenerative medicine. By definition stem cells are progenitor cells capable of self-renewal and differentiation hypothetically “ad infinitum” into more specialized cells and mature tissue. Stem cells are commonly classified based on the developmental stage from which they are isolated, although this has been a source of debate amongst stem cell scientists. A commonly accepted approach classifies stem cells into three different groupings: Embryonic Stem Cells (ESCs), Umbilical Cord Stem Cells (UCBSCs) and Adult Stem Cells (ASCs), which includes stem cells from bone marrow (BM), fat tissue (FT), engineered induced pluripotent (IP) and peripheral blood (PB). The increasing emergence of evidence in support of the clinical effectiveness of stem cells has had dramatic implications in our understanding of degenerative disease progression offering the opportunity to develop novel therapeutics that specifically target and eradicate the inherent cause. This review aims to provide an overview of the recent developments in the field of multipotent and pluripotent stem cell new models and therapeutics, embodied in the form of patent documents. Therefore, we refer to a wide range of inventions, with their existing development number of patented clinical trials, which suggest stem cells specific benefits as future degenerative disease guideline uses. Keywords: Bio-material, extra-cellular matrix, multipotent stem cells, pluripotent stem cells.
El Editor Cientifico y Editor Tecnico de Maderas, Ciencia y Tecnologia agradecen a los revisores por su asistencia como arbitros en los procesos de revision por pares de la revista. La calidad de los contenidos cientificos de Maderas, Ciencia y Tecnologia depende del trabajo a conciencia de los colaboradores. Apreciamos su esfuerzo en la revision de los manuscritos y valoramos enormemente su disponibilidad para compartir su tiempo y experiencia con la Revista Maderas, Ciencia y Tecnologia. Apreciamos su evaluacion cuidadosa de los manuscritos recibidos durante 2014-2015.
Regenerative medicine seeks to restore normal architecture and function of tissues which have been damaged by disease, trauma and/or ageing. Stem cells are known to be an integral part of any regeneration process. Their isolation or generation, in vitro expansion, recruitment and transplantation to the damaged sites are being heavily pursued. Several applications of pluripotent cell derivatives have arrived at the clinical stage and are offering promising results. Stem cells themselves or their products can exert desired functions in regeneration. The source of stem cells for developing therapies is vast and developments have been made at a very fast pace during the last ten years. Pluripotent stem cells from discarded embryos or induced from postnatal tissues are at the base of these investigations as they can theoretically be permanently cultured in vitro and can be triggered to differentiate any cell in the human body. Induced or directed differentiation of these cells is still being studied and generally the process involves long manipulations and thorough selection, which prevent pluripotent cells from being useful in autologous transplants. So-called adult stem cells or stem cells isolated from postnatal individuals offer the possibility to develop autologous sources for cell therapies. Bone marrow, cord and peripheral blood, fat and oral mucosa are sources of such stem cells. In this case the drawbacks are the availability in sufficient numbers to develop the regenerative protocols and the limited applications of these cells due to their limited differentiation ability. Both pluripotent and adult stem cells are being investigated for the development of clinical trials at the moment. Pluripotent stem cells will be able to be applied widely in cell therapy when directed differentiation can be controlled to the point of producing safe and functional derived cells and tissues. The present review will focus on recent patents on directed differentiation of pluripotent stem cells to derivatives with potential therapeutic value. Keywords: Cell engraftments, directed differentiation, ectoderm, endoderm, functional differentiation, mesoderm, pluripotent derivatives.
Cancer stem cells (CSCs) are believed to cause cancer recurrence because they resist conventional therapies and restart the growth of tumor cells. CSCs has a specific biological behavior, mainly due to a deregulation of the self-renewal capacity. These cells differ in division and the cell cycle, replication capacity in DNA repair, and deregulation of signaling pathways. Collectively, these results give CSC a malignant phenotype. This review focuses on CSCs oncology patents in the years 2011-2015. Because many inventions have recently been registered in relation to stem cells, our attention focuses on cancer-utility CSCs patents. The patents selected have been analyzed based on their therapeutic usefulness in the area of cancer, and we have detected a clear increase in interest, so that the data of patent applications filed in 2014 is highly significant. Compared with the total for 2013, patents have multiplied by 8.01. On the other hand, 59.57% of all selected patents were useful in oncology in general, opening new therapeutic perspectives for identifying CSCs. We also analyzed the interests of different countries in advancing knowledge in the area of the CSCs as a therapeutic tool for tumors. Some 38% of these patents are registered in the EU, while other countries showed fewer patents in this field of pathologies. Keywords: Cancer stem cell, cancer therapy, patent classification, tumor utility patent.
Intellectual property rights are increasingly seen as critical to the survival and growth of new and emerging technologies, such as stem cell research. Breakthrough technologies are swiftly patented (i.e. WARF and Yamanaka) but not without ample obstacles. Too early in the research development and patents issued often overreach broadly and wreak havoc on any future scientific developments. In fact, the establishment and the use of human pluripotent stem cells have proven complicated and problematic. Old broad patents claiming methods that cannot not replicate are, preventing development of newer, simpler and more effective technologies. On the other hand, the European patenting situation is deemed unfair against European scientists who cannot patent their human embryonic stem cell developed methods or cells, whereas others in different countries can perfectly do so. Nonetheless, the human pluripotent stem cell area is rapidly expanding and this is increasingly reflected in the global patent landscape. This review briefly discusses the present pluripotent stem cell environment using examples of worldwide patents with an emphasis on the United States, European Union and Sweden. It continues with the latest legal challenges in the United States and Europe and follows up with remarks on the current and future developments in this area. Keywords: Global patents, human embryonic stem cells, induced pluripotent patents, regenerative medicine, stem cells, US patents.
Cosmetic and reconstructive surgery relies extensively on the complex relationship between skin, soft tissue and the underlying bone skeleton. Soft tissue loss and acquired soft tissue deficits are some of the daily challenges faced by the plastic surgeon. Fat grafting has become one of the standard lines of care that has various applications in plastic surgery treatments. The ability of adipose stem cells to rejuvenate tissues is promising for plastic surgery. Bone disorders, including infection and poor healing, pose vexing problems to the reconstructive surgeon. Vascular surgery is a technique necessary for the reconstruction of the most challenging surgical defects, and has great potential for improvement through technology. Recent patents discussed in this article demonstrate promise to dramatically improve a number of specific patient conditions. Nanoscale refinements of current techniques may offer more efficient and improved surgical and non-surgical approaches for reconstruction. Such refinements will significantly expand our capabilities for innovative reconstructive interventions, with high efficiency, specificity and minimal invasiveness. Keywords: Bone reconstruction, fat graft, nanotechnology, patent, plastic and reconstructive surgery, regenerative medicine, vascular surgery.
Human pluripotent stem cells in their characteristics of immortal self-renewal and pluripotency have gained high expectations during last fifteen years regarding their ability to cure near any human disease. Regenerative Medicine was the new term for the novel cell-based treatments, which had the possibility of curing genetic diseases as well by previous correction of endogenous mutations in patient-specific induced pluripotent stem (iPS) cells. The possibility of developing combined genetic/ stem cell therapies for at least inherited monogenic diseases, meanwhile surpassing ethical rightness to destroy otherwise non-usable human embryos, still raised even more interest in the field of translational pluripotency. Aternative sources of stem cells from adult human tissues, gave rise to the research competition between the pluripotent stem and adult stem cells. The latter surpassed ethical debates but imposed slowness on the development of the field to translational medicine: these cells were multipotent in their vast majority, not immortal, and obtaining relevant amounts for research was more difficult compared to pluripotent stem cells. Despite their advantages in terms of availability, induced pluripotent cells have been mainly obtained by means of genetic modification, which impairs safeness of the downstream therapeutic product. The present review outlines the most recent inventions related to the preparation of safe clinical-grade hIPS cells. Its main objective is to contribute a concise compilation of the advances in the reprogramming of adult cells to pluripotency, the choice of original tissues and cell types, the methods of reprogramming to pluripotency, and above all the alternatives for elimination of genetic material from the reprogramming protocol. Registered patents and related bibliography reported mostly from the past two years have been reviewed, although basic literature has been included where needed to explain recent developments. Keywords: Chemical reprogramming, genetically intact, naive pluripotent stem, patient-specific, pluripotent, reprogramming, therapy.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Reliable treatment options for this disease are limited due to complexity and multifactorial causes of motor neuron damage. Cell therapy might be a promising treatment for ALS. Numerous preclinical studies have validated the feasibility of cell therapy using various cell types and routes of administration. These cell therapy approaches largely take one of two distinct therapeutic strategies: neuroprotection or motor neuron replacement. Despite some promising results, the success of cell therapy in ALS might rely on a combinative strategy that exploits the benefits of both neuronal cell protection and replacement. Although, ongoing clinical trials provide promising results in cell therapy for treatment of ALS patients, some challenges still facing potential cell therapy development. In this review, current cell products and patent technology related to cell therapeutic strategies are discussed. A detailed discussion of this topic might offer vital insight into the future and viability of cell therapy for ALS. Keywords: ALS, cell replacement, cell therapy, clinical trials, neuroprotection, patents.
In recent years, cell-based therapies have gained great enthusiasm as a new therapeutic approach for addressing many disorders. Many researchers have shown the roles of stem cells in replacing damaged tissues and in providing extracellular factors that can promote endogenous cellular replenishment. Also, stem cells are rich source of soluble factors and microvesicles, which are released from their surfaces and thereby exerting paracrine effect. Although pluripotent stem cells are considered the cornerstone in regenerative medicine, various types of more differentiated adult stem and progenitor cells are exploited. In this review, we provide an overview about the recent advances in the field of regenerative medicine and stem cell therapies for diabetes, cardiovascular and neurodegenerative diseases, with special interest in the recent patents. Patents from WIPO, USPTO, Patent scope and European patent databases have been discussed. In conclusion, the increasing number of patents and the extensive scientific research suggests that stem cell therapies hold a promising future for the management of incurable diseases. Keywords: Brown adipose tissue, cardiovascular diseases, diabetes, heart regeneration, islet regeneration, neurodegenerative disorders, stem cell therapy.
Experimental works in the field of reconstructive plastic surgery have been especially focused in restorative procedures based on flaps and peripheral nerve regeneration. Those involving the use of VEGF gene therapy showed generated particular interest but also many significant conclusions in both fields of reconstructive surgery which are currently introducing in the operating room. Interestingly, composite tissue allotransplantation methods joined the possibility to perform anatomical and functional reconstructions, since skin, muscle or bones can be transferred together, but also the concomitant nerves, which will be responsible to produce the movements of these transplanted tissues like in facial transplantation or limb transplantation. During reconstructive surgeries involving flaps, partial or complete ischemia of tissues can be a common complication, especially after free tissue transfer. For this reason, there is always a reasonable risk of flap necrosis that can lead to the loss of the reconstructive procedure due to venous or/and arterial insufficiency. On the other hand, after nerve damage, axons distal to the nerve crush begin to degenerate. As a consequence, the functional connections between motor axons and muscles are finally damaged leading to progressive muscle atrophy. When nerve continuity is repaired, the proximal stumps of injured axons are in condition to sprout within the distal nerve stumps. Experimental studies demonstrated the utility and efficiency of growth factors in stimulating neoangiogenesis in order to improve flap survival as well as in the promotion of axonal sprouting which is an important point for nerve regeneration. Among the ones, the Vascular Endothelial Growth Factor (VEGF) has shown to be an efficient therapeutic agent in both fields. Gene therapy based on adeno-associated viruses, liposomes or nanoparticles is the accepted method to develop the new angiogenesis and nerve promotion as these carriers are able to efficiently deliver therapeutic genes to flaps and nerves. Nevertheless, there are still many obstacles to be solved like the therapeutic maintenance of VEGF production along the period of time necessary to perform the desired effects, but also the use of VEGF as a preventive factor to avoid flap failure in reconstructive procedures. This reviews describes the advances in regenerative medicine in flap and nerve surgery using VEGF gene therapy and related patents. Keywords: Adenovirus, flaps, gene therapy, liposomes, nanoparticles, nerve regeneration, peripheral nerve, reconstructive surgery, VEGF.
Myocardial infarction results in loss of cardiac muscle and deficiency in cardiac performance. Likewise, peripheral artery disease can result in critical limb ischemia leading to reduced mobility, non-healing ulcers, gangrene and amputation. Both of these common conditions diminish quality of life and enhance risk of mortality. Successful advances in treatment have led to more people surviving incidences of myocardial infarction or living with peripheral artery disease. However, the current treatments are inadequate in repairing ischemic tissue. Over the last 5 years, a vast number of patents have been submitted concerning the use of stem cells, which correlates with the exponential growth in stem cell publications. Exploiting stem cell therapy offers a real potential in replacing ischemic tissue with functional cells. In this paper, we review recent patents concerning stem cell therapy that have the potential to provide or potentiate novel treatment for ischemic cardiovascular disease. In addition, we evaluate the promise of the inventions by describing some clinical trials that are currently taking place, as well as considering how current research on ischemic cardiovascular disease may change the patent landscape in the future. Keywords: Cardiovascular, cell therapy, heart, ischemia, regenerative medicine, stem cells.
Cardiovascular diseases represent the first cause of death in industrialized countries. To date, cardiac surgery is still considered the preferential treatment especially for those patients with severe heart failure. For these reasons, over the years the number of patents and applications in the cardiothoracic surgical area has notably improved probably than any other research field, starting from heart valves, devices and stents and including today the modern tissue engineering such as 3D scaffolds, patches and tissues. In this paper, we review the last recent patents specifically relevant to cardiothoracic surgery, beyond a simple description of inventions; we have also attempted to offer a broad overview on the scientific background and to highlight issues that still need to be addressed in the next future. Keywords: Cardiothoracic-surgery, devices, scaffolds, stents, tissue engineering.
