Patient and public perspectives on cell and gene therapies: a systematic review.

Cell and gene therapies offer opportunities for treating disease with potential to restore function, and cure disease. However, they are not without risk and pose complex logistical, economic, ethical and social challenges for health systems. Here we report our systematic review of the current evidence on patient and public knowledge and perspectives of cell and gene therapies, to inform future research, education and awareness raising activities. We screened 10,735 titles and abstracts, and evaluated the full texts of 151 publications. The final selection was 35 publications. Four themes were generated from the narrative synthesis of the study findings namely: (1) Knowledge and understanding of cell and gene therapies, (2) Acceptance of cell and gene therapies (3) Understanding of risk and benefits of therapy, and (4) Information needs and current sources of information. As potential funders or future recipients, it is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the debate. This review highlights the need for appropriate patient and public education on the various aspects of cell and gene therapies. High quality studies exploring patient and public opinions and experiences of cell and gene therapy are required. Patient and public perceptions of these therapies, alongside evidence of clinical and cost-effectiveness, will be central to their uptake and use.

Ethics and Policy for Bioprinting.

3D bioprinting involves engineering live cells into a 3D structure, using a 3D printer to print cells, often together with a compatible 3D scaffold. 3D-printed cells and tissues may be used for a range of purposes including medical research, in vitro drug testing, and in vivo transplantation. The inclusion of living cells and biomaterials in the 3D printing process raises ethical, policy, and regulatory issues at each stage of the bioprinting process that include the source of cells and materials, stability and biocompatibility of cells and materials, disposal of 3D-printed materials, intended use, and long-term effects. This chapter focuses on the ethical issues that arise from 3D bioprinting in the lab-from consideration of the source of cells and materials, ensuring their quality and safety, through to testing of bioprinted materials in animal and human trials. It also provides guidance on where to seek information concerning appropriate regulatory frameworks and guidelines, including on classification and patenting of 3D-bioprinted materials, and identifies regulatory gaps that deserve attention.

Ethical and Safety Issues of Stem Cell-Based Therapy.

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Report on Liver Cell Transplantation Using Human Fetal Liver Cells.

In an era of organ shortage, human fetuses donated after medically indicated abortion could be considered a potential liver donor for hepatic cell isolation. We investigated transplantation of fetal liver cells as a strategy to support liver functionality in end-stage liver disease. Here, we report our protocol of human fetal liver cells (hFLC) isolation in fetuses from 17 to 22 gestational weeks, and our clinical procedure of hFLC transplantation through the splenic artery.

Stepping Into and Out of the Void: Funding Dynamics of Human Embryonic Stem Cell Research in California, Sweden, and South Korea.

Nonprofit organizations and philanthropists stepped into a funding void caused by controversies over public funding of human embryonic stem cell (hESC) research. Based on interviews of 83 representatives of 53 funders, we examine the motivations and accountability structures of public agencies, corporations, fundraising dependent nonprofit organizations and philanthropic organizations that funded hESC research in three jurisdictions: California, Sweden, and South Korea. While non-traditional forms of funding are essential in the early stages of research advancement, they are unreliable for the long timeframes necessary to advance cell therapies. Such funding sources may enter the field based on high expectations, but may exit just as rapidly based on disappointing rates of progress.

Business oriented EU human cell and tissue product legislation will adversely impact Member States' health care systems.

The transplantation of conventional human cell and tissue grafts, such as heart valve replacements and skin for severely burnt patients, has saved many lives over the last decades. The late eighties saw the emergence of tissue engineering with the focus on the development of biological substitutes that restore or improve tissue function. In the nineties, at the height of the tissue engineering hype, industry incited policymakers to create a European regulatory environment, which would facilitate the emergence of a strong single market for tissue engineered products and their starting materials (human cells and tissues). In this paper we analyze the elaboration process of this new European Union (EU) human cell and tissue product regulatory regime-i.e. the EU Cell and Tissue Directives (EUCTDs) and the Advanced Therapy Medicinal Product (ATMP) Regulation and evaluate its impact on Member States' health care systems. We demonstrate that the successful lobbying on key areas of regulatory and policy processes by industry, in congruence with Europe's risk aversion and urge to promote growth and jobs, led to excessively business oriented legislation. Expensive industry oriented requirements were introduced and contentious social and ethical issues were excluded. We found indications that this new EU safety and health legislation will adversely impact Member States' health care systems; since 30 December 2012 (the end of the ATMP transitional period) there is a clear threat to the sustainability of some lifesaving and established ATMPs that were provided by public health institutions and small and medium-sized enterprises under the frame of the EUCTDs. In the light of the current economic crisis it is not clear how social security systems will cope with the inflation of costs associated with this new regulatory regime and how priorities will be set with regard to reimbursement decisions. We argue that the ATMP Regulation should urgently be revised to focus on delivering affordable therapies to all who are in need of them and this without necessarily going to the market. The most rapid and elegant way to achieve this would be for the European Commission to publish an interpretative document on "placing on the market of ATMPs," which keeps tailor-made and niche ATMPs outside of the scope of the medicinal product regulation.

Is iPS cell the panacea?

In 2006, it was reported that transgenic expression of merely four defined transcription factors (c-Myc, Klf4, Oct4, and Sox2) is sufficient to reprogram somatic cells to a pluripotent state. The resulting induced pluripotent stem (iPS) cells ignited intense interest in the field of life science for their promising applications in basic biology, drug development, and transplantation. However, the underlying problems of iPS cells seem to be ignored. This review shed light on the problems pertaining iPS cells, including the elusive origin, risk of tumorgenesis, and its relationship with natural selection.

Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.