Current Stem Cell Research & Therapy - Volume 10, Issue 3, 2015

Pluripotent stem cells (PSCs) derived from somatic cells represent a powerful experimental tool for investigating the molecular mechanisms underlying the disease phenotype; with prospects to advance medical therapies. They also have significant potential as a renewable source of autologous cells for cellular therapy. Various approaches for PSC derivation from somatic cells have been reported in the literature. The method used for reprogramming is particularly relevant as it may affect the characteristics and quality of PSCs. This review will present an overview of the basic strategies and methods for reprogramming to pluripotency. These strategies will be briefly discussed in the context of how the mechanism of reprogramming could influence PSC characteristics with respect to safety and quality. Aspects of the reprogramming approach that can influence PSC properties, such as culture conditions and donor cell source, are also discussed.

Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic stem cells (ESCs), but circumvent most of the ethical issues surrounding ESCs. The use of iPSCs to treat liver diseases is gaining increasing interest. Recent studies show these iPSCs can be differentiated into the hepatic lineage and provide an accurate model for liver diseases, drug screening and drug toxicity testing. Recently, the potential application of iPSC-derived hepatocytes to be used in cell-based therapies has been explored as a novel strategy to treat human liver disease. However, the successful use of these iPSC-derived hepatocytes hinges on overcoming the inherent problems of using iPSC in cell-based therapies. Given these problems are addressed in the future, these iPSC derived hepatocytes provide a limitless supply of cells that could be used to treat liver diseases not only in screening and toxicity testing but also in cell-based therapies.

The development of induced pluripotent stem cells (iPSCs) has shown a great potential in disease modeling, drug screening, organ reconstruction and cancer therapy. Hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC), particularly in Western countries. However, HCV infection has never been fully understood because the culprit virus only preferably infects human and chimpanzee. Hepatocyte-like cells derived from human iPSCs have been reported to be susceptible to infection with HCV and may serve as an appropriate model for HCV infection. Recently, the field of HCV research has been revolutionized by the finding that pigtail macaque (Macaca nemestrina) hepatic cells derived from iPSCs support the entire HCV life cycle, and pigtail macaques may serve as a suitable, clinically relevant model for the study of HCV infection. Moreover, the technologies generating vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro have also been established. These findings will play a very important role in understanding the mechanism of HCV infection and therapy for HCV related HCC.

Induced pluripotent stem cells (iPSCs) technology provides unique possibilities for human disease modeling and novel therapeutic approach in regenerative medicine. By applying this technology, it is possible to establish highfidelity human disease models from biopsy samples of different individuals with various genetic backgrounds. This may provide a better understanding of patient-specific pathophysiological processes of a wide variety of diseases. Stem cell-derived intestinal epithelia and human intestinal organoids (HIOs) generated in vitro, for example, can faciliate drug screening and modeling of inflammation-associated gastrointestinal diseases. In this review, we highlight novel achievements of generating disease-related iPSCs and discuss their potential applications in the modeling of gastrointestinal disorders. The critical influencing factors, main limitations and possible improvements in the process of iPSCs-based disease modeling are also discussed.

Inflammatory bowel diseases (IBDs) are chronic and involve the gastrointestinal tract; the two primary IBDs are ulcerative colitis and Crohn’s disease. Existing treatments for IBD include control of active inflammation and regulation of immune disorders, and commonly used drugs include salicylates, corticosteroids, and immunosuppressants. At the same time, an in-depth study of IBD pathogenesis promoted the acceptance of bioimmunotherapy by increasing numbers of people. However, long-term use of these drugs can cause adverse reactions that are difficult for patients to overcome, with limited efficacy for critically ill patients. Recent studies have found that stem cell transplantation is a new and effective therapy and IBD treatment, particularly for refractory cases. Stem cells, especially induced pluripotent stem cells (iPSCs), can differentiate into functional intestinal epithelia and their use avoids ethical issues arising from embryonic stem cells, providing a new kind of seed cell for alternative treatments for IBD. This paper reviews iPSCs as a potential new treatment for IBDs in order to provide an experimental and clinical reference.

It has been demonstrated that mouse and human somatic cells can be reprogrammed into an embryonic stem cell-like state by introducing combinations of the transcription factors. The generation of such induced pluripotent stem cells (iPSCs) has enabled the derivation of disease-specific pluripotent cells which opens up new avenues of disease modeling and provides valuable experimental platforms. Moreover, technologies for creating humanized animal models by human iPSCs will be available as well, which will increase the utility of humanized mice for research. Emerging evidences suggest, however, that immunogenicity of iPSCs seems to be a vital and controversial issue surrounding potential of iPSCs. Recent studies on induced multipotent progenitor cells (iMPCs) extend the applications of iPSC technology and provide promising candidates for disease modeling. In this review, we introduce a wide range of applications of iPSCs in disease modeling and discuss the immune response on the use of iPSCs as well as a promising alternative for future directions of disease modeling.

Connections between inflammation and cancer are a rapidly developing field. Some gastrointestinal tract cancers arise from infection, chronic irritation, and ensuing inflammation. Cellular effectors and mediators are important constituents of the tumor microenvironment, including neoplastic, stromal, and migratory hematopoietic cells. Complex interaction between these cells in the tumor microenvironment regulates tumor growth, progression, metastasis, and angiogenesis. Tumor-associated macrophages represent the major inflammatory cell population in tumors, which orchestrate various aspects of cancer. Cytokines and chemokines are major mediators of communication between cells in the tumor microenvironment. The concept of oncogene builds up an inflammatory pre-neoplastic microenvironment has emerged in the last few years. On the other hand, the development of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research. However, there are still some debates about iPSCs which should be answered by science.

Gastrointestinal motility disorders affect millions of people worldwide, resulting in significant morbidity and mortality. Current treatments for these disorders are inadequate and often provide little to no relief for patients. As a result, gastrointestinal motility disorders produce substantial long-term social and economic burdens in both developed and developing countries. These limited treatment options arise largely from our relatively poor understanding of the molecular etiology for the majority of gastrointestinal motility disorders. In turn, this is due to our limited access to normal or diseased human gut tissue for use in research. In particular while the interstitial cells of Cajal (ICC) are known to be important for gastrointestinal motility, little is known of how these cells function or how they are involved in disease initiation and progression. The advent of human pluripotent stem cell technology offers an opportunity to generate large amounts of human tissue for both research and clinical applications. The application of this technology to gastrointestinal motility disorders is currently only in its infancy and as yet no studies have described ICC production from human pluripotent cells. By considering the present understanding of the anatomical, cellular and molecular basis of gut motility with particular emphasis on ICC, this review provides a clear framework for the application of human pluripotent stem cell technology to answer fundamental questions of ICC involvement in gut motility.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by the progressive photoreceptors and pigment epithelial cells dysfunction. It is the most common retinal degeneration, responsible for loss of vision of most people worldwide. Until now its exact pathogenesis and etiology are not clear. So far there is no approved therapy. New approaches for RP therapy include cell transplantation, gene therapy, cytokine therapy, nutrition therapy, and hyperbaric oxygen therapy. Such therapies for retinal degenerative diseases are limited in their efficacy. This paper reviews the relevant documents, especially recent researches, and reviews advances in the treatment of RP.

Stem cell therapy for patients with diabetes is an area of great interest to both scientists and clinicians. Human umbilical cord blood cells (HUCBCs) are being increasingly used as a source of stem cells for cell-based therapy for diabetes because these cells can differentiate into pancreatic islet β-cells. Administration of HUCBCs has been shown to lower blood glucose levels in diabetic animal models. The use of autologous HUCBC transfusion in type 1 diabetic children has not shown any benefit. However, “Stem Cell Educator” therapy has shown promise in long term lowering of blood glucose levels in both type 1 and type 2 diabetic patients. In this review, we will briefly discuss recent advances in HUCBC therapy in the treatment of diabetes and some of its complications.

Despite the numerous recent advances made in conventional anticancer therapies, metastasis and recurrence still remain the major problems in cancer management. The current treatment modalities kill the bulk of the tumor, leaving cancer stem cells behind and therefore, the agents specifically targeting this cancer initiating cell population may have important clinical implications. In this review article, the data about the inhibitory action of flavonoids, both natural as well as their synthetic derivatives, on the self-renewal capacity and survival of cancer stem cells of different origins are compiled and analyzed. These data indicate that several plant secondary metabolites, including soy isoflavone genistein, green tea catechins and a widely distributed flavonol quercetin, have the potential to suppress the stemness markers and properties, traits of the epithelial-to-mesenchymal transition and migratory characteristics, being also able to sensitize these cells to the standard chemotherapeutic drugs. These polyphenolic compounds act through multiple signal transduction pathways, providing thus the maximal therapeutic response and offering some promise to be included in the future cancer treatment schemes in combination with the conventional therapies. Such approach may give an important contribution to the shift of cancer management from palliative to curative mode, likely leading to the disease-free survival. Thus, flavonoids can serve as attractive candidates for novel anticancer agents by eliminating the roots of cancer.