Variability in supply, paucity of donors and cellular instability under in vitro conditions have limited the application of primary human hepatocytes (PHHs) to hepatotoxicity testing. Therefore, alternative sources have been sought for functional liver cells. Many of the earlier in vitro hepatotoxicity studies were carried out using hepatoma-derived cell lines. These cell lines have overcome some of the limitations of PHHs with regard to phenotypic stability and availability; however, they suffer from their own inherent limitations, such as the lack of drug-metabolizing functionality, which renders them inadequate for situations where toxic metabolite formation of the parent drug occurs. In the last decade we have witnessed a burgeoning interest of the research community in using hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) as in vitro hepatotoxicity models. HLCs offer the perspective of a defined and renewable supply of functional hepatocytes; more importantly, HLCs maintain their original donor genotype and afford donor diversity, thus opening new avenues to patient-specific toxicity testing. In this review, we first introduce various in vitro hepatotoxicity models, then focus on HLCs and their application in hepatotoxicity studies, and finally offer some perspectives on future developments of the field.

More research is being conducted on myocardial cell treatments utilizing stem cell lines that can develop into cardiomyocytes. All of the forms of cardiac illnesses have shown to be quite amenable to treatments using embryonic (ESCs) and induced pluripotent stem cells (iPSCs). In the present study, we reviewed the differentiation of these cell types into cardiomyocytes from an epigenetic standpoint. We also provided a miRNA network that is devoted to the epigenetic commitment of stem cells toward cardiomyocyte cells and related diseases, such as congenital heart defects, comprehensively. Histone acetylation, methylation, DNA alterations, N6-methyladenosine (m6a) RNA methylation, and cardiac mitochondrial mutations are explored as potential tools for precise stem cell differentiation.

A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.

Vision represents one of the main senses for humans to interact with their environment. Our sight relies on the presence of fully functional light sensitive cells - rod and cone photoreceptors - allowing us to see under dim (rods) and bright (cones) light conditions. Photoreceptor degeneration is one of the major causes for vision impairment in industrialized countries and it is highly predominant in the population above the age of 50. Thus, with the continuous increase in life expectancy it will make retinal degeneration reach an epidemic proportion. To date, there is no cure established for photoreceptor loss, but several therapeutic approaches, spanning from neuroprotection, pharmacological drugs, gene therapy, retinal prosthesis, and cell (RPE or photoreceptor) transplantation, have been developed over the last decade with some already introduced in clinical trials. In this review, we focus on current developments in photoreceptor transplantation strategies, its major breakthroughs, current limitations and the next challenges to translate such cell-based approaches toward clinical application.

The successful generation of the first iPSCs about ten years ago has provided deeper insight into previously unknown disease mechanisms and therapeutic opportunities for many diseases. In particular, iPSCs are becoming an important tool in advancing modeling and therapeutic intervention for Alzheimer\'s disease. In this manuscript, we assess the research climate surrounding the application of iPSCs to familial and sporadic Alzheimer\'s disease, including the generation and isolation of individualized neural stem cells, the introduction of neural stem cell transplants using iPSCs, and an estimation of the potential use of iPSCs as research models for Alzheimer\'s treatments and therapies. The clinical application of stem cells in the treatment of Alzheimer\'s disease appears promising, but much of the recent experimentation has been conducted using animal models or embryonic stem cells. As induced pluripotent stem cell research advances, iPSCs will likely provide investigators with a more applicable tool to progress advances in research and treatment for Alzheimer\'s and other neurodegenerative diseases.

Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.

Stem cells have the remarkable potential to develop into many different cell types, essentially without limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer\'s disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic \"somatic\" or \"adult\" stem cells. Recent breakthrough make it possible to convert or \"reprogram\" specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly discuss the recent progresses in this area.

Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the exogenous expression of defined transcription factors. iPSCs share the defining features of embryonic stem cells (ESCs) in that they are able to self renew indefinitely and maintain the potential to develop into all cell types of the body. These cells have key advantages over ESCs in that they are autologous to the donor cells and can be generated from individuals at any age. iPSCs also circumvent ethical and political issues surrounding the destruction of embryos that is necessary in the isolation of ESCs. This review briefly describes the advent of iPSC technology and the concepts of nuclear reprogramming, and discusses the potential application of this powerful biological tool in both surgical research and regenerative medicine.

Cellular reprogramming can offer valuable insight into disease mechanism and has the potential to provide novel tools for regenerative medicine. Yet it remains an inefficient and often incomplete process. However, experiments show that almost all somatic cells eventually give rise to the pluripotent state, albeit at different latencies, as long as expression of reprogramming transcription factors is maintained. Furthermore, it appears that specific subpopulations of cells can be identified that show enhanced propensities to be reprogrammed to the pluripotent state. It has been proposed that an initial stochastic process is responsible for this initial priming that is followed by a deterministic process that directs the primed cells into the pluripotent state. Here, we propose a population shift view of cellular reprogramming, which explains these observations and reconciles the stochastic and deterministic nature of this process. According to this view, a small population of cells, whose states are closer to the pluripotent state and reside in pre-existing energetically favorable trajectories, will be initially selected for reprogramming. Moreover, by maintaining ectopic expression of reprogramming factors, other cells enter these pathways as a result of transcriptional and epigenetic stochastic variations. Consequently, increasing numbers of cells reach the pluripotent state, and the cell population distribution shifts toward this state. Importantly, additional perturbations can change the epigenetic landscape, allowing cells more access to the reprogramming trajectories, thereby increasing reprogramming efficiency. Knowledge of the initial cellular subpopulations and pathways of states that lead to the final cellular state should allow us to design alternative perturbation strategies to improve reprogramming efficiency and fidelity.

Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases.