The successful derivation of human embryonic stem cell (hESC) lines from the in vitro fertilization (IVF) leftover embryos little over a decade ago is considered as one of the major breakthroughs of the 20th century life sciences. The hESCs, derived from the inner cell mass (ICM) or epiblast of human blastocyst, are genetically stable with unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of a large supply of human disease-targeted human somatic cells that are restricted to the lineage in need of repair. Therefore, they have been regarded as an ideal source to provide an unlimited supply of large-scale well-characterized human specialized cell types for cell-based therapies to resolve some worldwide major health problems, such as neurodegenerative diseases, paralysis, diabetes, and heart diseases. Most recently, the IVF pioneer Robert Edwards was awarded last year’s Nobel Prize in physiology or medicine. The Noble prize recognition to the IVF techniques comes to light that a small portion of the millions of excess embryos currently stored in the IVF clinics worldwide, which are otherwise destined for destruction, could potentially be an unlimited source to deliver in the future a whole range of therapeutic treatments for tissue and function restoration in patients with life-threatening diseases and injuries.
US patents directed to human stem cell technologies have generated intense interest as well as controversy. Many patents relating to stem cell technology have faced reexamination, litigation, or both. The US Patent and Trademark Office (USPTO) recently upheld three Wisconsin Alumni Research Foundation (WARF) stem cell patents on the breadth, anticipation, and obviousness of the claims after reexamination requested by a third-party challenger in 2006. These WARF patents involve claims on hESCs as well as certain processes used to make such cells as divisional applications originated from primate embryonic stem cell patents. These WARF patents with extremely broad claims have casted a shadow over the commercialization of these cells as therapeutics in the US’ biotechnology market so far. While the controversies related to hESC patents in the US center on scientific and economic issues, in Europe, the patentability of hESCs has been met with fierce moral opposition. The European Patent Office (EPO) has refused to grant hESC patents based on its interpretation of the “European Directive on the Legal Protection of Biotechnological Inventions”, which holds unpatentable inventions concerning products of human stem cell cultures that can only be obtained by the use, involving their destruction, of human embryos. The EPO regards patents on hESCs as illegal because they are patents on a human body or human body part, offend human dignity, or involve commercial or industrial uses of embryos. However, in spite of controversy surrounding the ownership of hESCs, the number of patent applications related to hESCs is growing rapidly in the last 5 years. It will be of importance to fulfilling the therapeutic promise of hESCs that the hESC patents are placed in the context of the biotechnology and health industry and granted on inventions downstream in the value chain of regenerative medicine. To date, the USPTO has granted 92 hESC-related patents on the process for isolating, culturing, purifying, manipulating, or differentiating hESCs.
The hESC, derived from the inner cell mass or epiblast of the blastocyst, offers both a model system for human development and a potentially unlimited source of graft material for cell-based therapies. The pluripotence of hESCs implies such cells’ tremendous potential for tissue and function restoration, whereas it has vacated a practical approach to generate a large supply of uniform replacement cells from hESCs for treating diseases. How to channel the wide differentiation potential of human pluripotent cells efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation of their therapeutic potential. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ-layer differentiation, which yields mixed populations of cell types that may reside in three embryonic germ layers and often makes desired differentiation not only inefficient, but uncontrollable and unreliable as well. Following transplantation, these hESC-derived grafts tend to display not only a low efficiency in generating the desired cell types necessary for reconstruction of the damaged structure, but also phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity. In view of growing interest in the use of human pluripotent cells, teratoma formation and the emergence of inappropriate cell types have become a constant concern following transplantation. Developing more practical approaches that permit to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype is vital to harnessing the power of hESC biology for safe and effective clinical translation.
Standard stem cell differentiation protocols involve cultivation in 2-dimensional (2D) settings, whereas in vivo organogenesis requires a 3D setting to provide the spatial and temporal controls of cell differentiation necessary for the formation of functional tissues. The traditional methods of 2D culture presently employed in the field often result in unpredictable stem cell function and behavior in vivo following transplantation. Developing strategies of complex 3D models of human embryogenesis and organogenesis will provide a powerful tool that enables more rigorous experimentation under conditions that are tightly regulated and authentically representing the in vivo spatial and temporal patterns. It will go beyond “flat biology” to increase the biological complexity of human-based in vitro models and assays to mimic the in vivo human organ systems and functions. Although ethical debate about the patentability of hESCs and policy makers on Funding issues are still lagging behind the scientific developments, in the case of many life-threatening diseases, supporting such research is crucial to driving the advance of medicine to provide optimal regeneration and reconstruction treatment options for the damaged or lost functional tissues and organs that have been lacking. For more information about this topic, please visit Dr. Parsons’ most recent review article “Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells” via the open access link at http://www.benthamscience.com/rpgm/openaccessplus.htm.
US patents directed to human stem cell technologies have generated intense interest as well as controversy. Many patents relating to stem cell technology have faced reexamination, litigation, or both. The US Patent and Trademark Office (USPTO) recently upheld three Wisconsin Alumni Research Foundation (WARF) stem cell patents on the breadth, anticipation, and obviousness of the claims after reexamination requested by a third-party challenger in 2006. These WARF patents involve claims on hESCs as well as certain processes used to make such cells as divisional applications originated from primate embryonic stem cell patents. These WARF patents with extremely broad claims have casted a shadow over the commercialization of these cells as therapeutics in the US’ biotechnology market so far. While the controversies related to hESC patents in the US center on scientific and economic issues, in Europe, the patentability of hESCs has been met with fierce moral opposition. The European Patent Office (EPO) has refused to grant hESC patents based on its interpretation of the “European Directive on the Legal Protection of Biotechnological Inventions”, which holds unpatentable inventions concerning products of human stem cell cultures that can only be obtained by the use, involving their destruction, of human embryos. The EPO regards patents on hESCs as illegal because they are patents on a human body or human body part, offend human dignity, or involve commercial or industrial uses of embryos. However, in spite of controversy surrounding the ownership of hESCs, the number of patent applications related to hESCs is growing rapidly in the last 5 years. It will be of importance to fulfilling the therapeutic promise of hESCs that the hESC patents are placed in the context of the biotechnology and health industry and granted on inventions downstream in the value chain of regenerative medicine. To date, the USPTO has granted 92 hESC-related patents on the process for isolating, culturing, purifying, manipulating, or differentiating hESCs.
The hESC, derived from the inner cell mass or epiblast of the blastocyst, offers both a model system for human development and a potentially unlimited source of graft material for cell-based therapies. The pluripotence of hESCs implies such cells’ tremendous potential for tissue and function restoration, whereas it has vacated a practical approach to generate a large supply of uniform replacement cells from hESCs for treating diseases. How to channel the wide differentiation potential of human pluripotent cells efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation of their therapeutic potential. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ-layer differentiation, which yields mixed populations of cell types that may reside in three embryonic germ layers and often makes desired differentiation not only inefficient, but uncontrollable and unreliable as well. Following transplantation, these hESC-derived grafts tend to display not only a low efficiency in generating the desired cell types necessary for reconstruction of the damaged structure, but also phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity. In view of growing interest in the use of human pluripotent cells, teratoma formation and the emergence of inappropriate cell types have become a constant concern following transplantation. Developing more practical approaches that permit to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype is vital to harnessing the power of hESC biology for safe and effective clinical translation.
Standard stem cell differentiation protocols involve cultivation in 2-dimensional (2D) settings, whereas in vivo organogenesis requires a 3D setting to provide the spatial and temporal controls of cell differentiation necessary for the formation of functional tissues. The traditional methods of 2D culture presently employed in the field often result in unpredictable stem cell function and behavior in vivo following transplantation. Developing strategies of complex 3D models of human embryogenesis and organogenesis will provide a powerful tool that enables more rigorous experimentation under conditions that are tightly regulated and authentically representing the in vivo spatial and temporal patterns. It will go beyond “flat biology” to increase the biological complexity of human-based in vitro models and assays to mimic the in vivo human organ systems and functions. Although ethical debate about the patentability of hESCs and policy makers on Funding issues are still lagging behind the scientific developments, in the case of many life-threatening diseases, supporting such research is crucial to driving the advance of medicine to provide optimal regeneration and reconstruction treatment options for the damaged or lost functional tissues and organs that have been lacking. For more information about this topic, please visit Dr. Parsons’ most recent review article “Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells” via the open access link at http://www.benthamscience.com/rpgm/openaccessplus.htm.
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