• Enhancement
• Ethics
• Nanomedicine
• Nanotechnology
• Risk
• Safety
• Social justice
• Uncertainty

• Bioethics
• Biomedical Research/ethics
• Humans
• Nanomedicine/ethics
• Nanomedicine/legislation & jurisprudence
• Nanoparticles/adverse effects
• Nanoparticles/therapeutic use
• Occupational Exposure/adverse effects
• Precision Medicine/ethics
• Regenerative Medicine/ethics
• Risk Assessment
• Translational Research, Biomedical/ethics
• Uncertainty
• Workplace

• First-in-human trials
• Human embryonic stem cells
• Preclinical benchmarks
• Research ethics
• Translational research

• Benchmarking/ethics
• Benchmarking/legislation & jurisprudence
• Cell Differentiation
• Cell Lineage
• Cell Survival
• Clinical Trials as Topic/ethics
• Clinical Trials as Topic/legislation & jurisprudence
• Embryonic Stem Cells/transplantation
• Humans
• Models, Animal
• Parkinson Disease/diagnosis
• Parkinson Disease/surgery
• Patient Safety
• Phenotype
• Policy Making
• Research Design/legislation & jurisprudence
• Risk Assessment
• Stem Cell Transplantation/adverse effects
• Stem Cell Transplantation/ethics
• Stem Cell Transplantation/legislation & jurisprudence
• Stem Cell Transplantation/methods
• Translational Research, Biomedical/ethics
• Translational Research, Biomedical/legislation & jurisprudence

There are two types of human pluripotent stem cells: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), both of which launched themselves on clinical trials after having taken measures to overcome problems: Blocking rejections by immunosuppressants regarding ESCs and minimizing the risk of tumorigenicity by depleting exogenous gene components regarding iPSCs. It is generally assumed that clinical applications of human pluripotent stem cells should be limited to those cases where there are no alternative measures for treatments because of the risk in transplanting those cells to living bodies. Regarding lifestyle diseases, we have already several therapeutic options, and thus, development of human pluripotent stem cell-based therapeutics tends to be avoided. Nevertheless, human pluripotent stem cells can contribute to the development of new therapeutics in this field. As we will show, there is a case where only a short-term presence of human pluripotent stem-derived cells can exert long-term therapeutic effects even after they are rejected. In those cases, immunologically rejections of ESC- or allogenic iPSC-derived cells may produce beneficial outcomes by nullifying the risk of tumorigenesis without deterioration of therapeutic effects. Another utility of human pluripotent stem cells is the provision of an innovative tool for drug discovery that are otherwise unavailable. For example, clinical specimens of human classical brown adipocytes (BAs), which has been attracting a great deal of attention as a new target of drug discovery for the treatment of metabolic disorders, are unobtainable from living individuals due to scarcity, fragility and ethical problems. However, BA can easily be produced from human pluripotent stem cells. In this review, we will contemplate potential contribution of human pluripotent stem cells to therapeutic development for lifestyle diseases.

• Arteriostenosis
• Human embryonic stem cells
• Glucose intolerance
• Human induced pluripotent stem cells
• Brown adipose tissue

• Cell therapy
• Iron oxide
• Labeling
• Magnetic targeting
• Neural cell
• OPC
• Tracking
• Uptake

Oligodendrocyte precursor cells (OPCs) have shown high promise as a transplant population to promote regeneration in the central nervous system, specifically, for the production of myelin – the protective sheath around nerve fibers. While clinical trials for these cells have commenced in some areas, there are currently key barriers to the translation of neural cell therapies. These include the ability to (a) image transplant populations in vivo; (b) genetically engineer transplant cells to augment their repair potential; and (c) safely target cells to sites of pathology. Here, we review the evidence that magnetic nanoparticles (MNPs) are a ‘multifunctional nanoplatform’ that can aid in safely addressing these translational challenges in neural cell/OPC therapy: by facilitating real-time and post-mortem assessment of transplant cell biodistribution, and biomolecule delivery to transplant cells, as well as non-invasive ‘magnetic cell targeting’ to injury sites by application of high gradient fields. We identify key issues relating to the standardization and reporting of physicochemical and biological data in the field; we consider that it will be essential to systematically address these issues in order to fully evaluate the utility of the MNP platform for neural cell transplantation, and to develop efficacious neurocompatible particles for translational applications.

• Cell therapy
• Iron oxide
• Labeling
• Magnetic targeting
• Neural cell
• OPC
• Tracking
• Uptake

• Cell therapy
• Clinical trials
• Combinatorial therapies
• Molecular therapy
• Pathophysiology
• Spinal cord injury

Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability of occurrence, and operation dimensions needed to effectuate favorable outcomes. Early human trials transform this uncertain landscape into one where there are grounds for belief about risk and benefit for various combined operation dimensions. To accomplish this, studies set out with two aims. First, they identify a set of operation dimensions that, when combined as a package (intervention ensemble), elicits a reasonable probability of a target outcome. Second, they define the boundaries of dimension values within an intervention ensemble. This latter aim entails exposing at least some volunteers in early studies to treatments that are inactive or excessive. I provide examples that illustrate the way early human studies discover and delimit intervention ensembles, and close by offering some implications of this framework for ethics, methodology, and efficiency in clinical development of new interventions.

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and are pluripotent, retaining the ability to differentiate into all cell types in the body. As a renewable source of various types of human cells, hESCs hold great therapeutic potential. Although significant advances have been achieved in defining the conditions needed to differentiate hESCs into various types of biologically active cells, many challenges remain in the clinical development of hESC-based cell therapy, such as the immune rejection of allogeneic hESC-derived cells by recipients. Breakthroughs in the generation of induced pluripotent stem cells (iPSCs), which are reprogrammed from somatic cells with defined factors, raise the hope that autologous cells derived from patient-specific iPSCs can be transplanted without immune rejection. However, recent genomic studies have revealed epigenetic and genetic abnormalities associated with induced pluripotency, a risk of teratomas, and immunogenicity of some iPSC derivatives. These findings have raised safety concerns for iPSC-based therapy. Here, we review recent advances in understanding the genomic and functional stability of human pluripotent stem cells, current challenges to their clinical application and the progress that has been made to overcome these challenges.

• Embryonic stem cells
• cell therapy
• epigenetics
• genetic stability
• immune rejection
• induced pluripotent stem cells

• spinal cord injury
• neural progenitor
• mesenchymal stem cell
• bone marrow
• clinical trial
• cell transplantation

• Cell Transplantation/methods
• Clinical Trials as Topic/methods
• Clinical Trials as Topic/trends
• Humans
• Spinal Cord Injuries/epidemiology
• Spinal Cord Injuries/surgery

Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway.

The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process.

This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.