Induced pluripotent stem cell technology: trends in molecular biology, from genetics to epigenetics.

Induced pluripotent stem cell (iPSC) technology, based on autologous cells' reprogramming to the embryonic state, is a new approach in regenerative medicine. Current advances in iPSC technology have opened up new avenues for multiple applications, from basic research to clinical therapy. Thus, conducting iPSC trials have attracted increasing attention and requires an extensive understanding of the molecular basis of iPSCs. Since iPSC reprogramming is based on the methods inducing the expression of specific genes involved in pluripotency states, it can be concluded that iPSC reprogramming is strongly influenced by epigenetics. In this study, we reviewed the molecular basis of reprogramming, including the reprogramming factors (OCT4, SOX2, KLF4, c-MYC, NANOG, ESRRB, LIN28 as well as their regulatory networks), applied vectors (retroviral vectors, adenoviral vectors, Sendaiviral vectors, episomal plasmids, piggyBac, simple vectors, etc.) and epigenetic modifications (miRNAs, histones and DNA methylation states) to provide a comprehensive guide for reprogramming studies.

Induced Pluripotent Stem Cell Meets Severe Combined Immunodeficiency.

Severe combined immunodeficiency (SCID) is classified as a primary immunodeficiency, which is characterized by impaired T-lymphocytes differentiation. IL2RG, IL7Ralpha, JAK3, ADA, RAG1/RAG2, and DCLE1C (Artemis) are the most defective genes in SCID. The most recent SCID therapies are based on gene therapy (GT) of hematopoietic stem cells (HSC), which are faced with many challenges. The new studies in the field of stem cells have made great progress in overcoming the challenges ahead. In 2006, Yamanaka et al. achieved "reprogramming" technology by introducing four transcription factors known as Yamanaka factors, which generate induced pluripotent stem cells (iPSC) from somatic cells. It is possible to apply iPSC-derived HSC for transplantation in patients with abnormality or loss of function in specific cells or damaged tissue, such as T-cells and NK-cells in the context of SCID. The iPSC-based HSC transplantation in SCID and other hereditary disorders needs gene correction before transplantation. Furthermore, iPSC technology has been introduced as a promising tool in cellular-molecular disease modeling and drug discovery. In this article, we review iPSC-based GT and modeling for SCID disease and novel approaches of iPSC application in SCID.

Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach.

Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.

A Review on Leukemia and iPSC Technology: Application in Novel Treatment and Future.

Leukemia is an uncontrollable growth of hematopoietic cells due to a mutation in DNA followed by cellular dysregulation and one or more chromosomal disorder that generally leads to a clonal abnormality. Theoretical and technical inability in early screening and distinguishing cancer, tumor tolerance to common treatment methods, repeated relapses of cancer after remission phase, heterogeneous chromosomal abnormality, and the side effects of current chemotherapies are some of challenges that we face with leukemia and other malignancies. Induced pluripotent stem cells (iPSC) opened a promising window to a wide range of diseases, including leukemia. Overcoming the barriers in leukemia is possible with iPSC technology. Induced hematopoietic stem cell transplantation (and gene therapy), induced cytotoxic T-lymphocytes and reprogrammed NK cells that strengthen the immune system, miRNAs, modeling approaches, and supportive cares are some aspects of the novel treatment based on iPSC technology.