Induced Pluripotent Stem Cells (iPSCs)—Roles in Regenerative Therapies, Disease Modelling and Drug Screening (original) (raw)
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Induced pluripotent stem cells and their use in cardiac and neural regenerative medicine
Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by Yamanaka and colleagues to induce pluripotency in somatic cells has reshaped the field of stem cell research. The complications related to the usage of pluripotent embryonic stem cells (ESCs) in human medicine, particularly ESC isolation and histoincompatibility were bypassed with induced pluripotent stem cell (iPSC) technology. The human iPSCs can be used for studying embryogenesis, disease modeling, drug testing and regenerative medicine. iPSCs can be diverted to different cell lineages using small molecules and growth factors. In this review we have focused on iPSC differentiation towards cardiac and neuronal lineages. Moreover, we deal with the use of iPSCs in regenerative medicine and modeling diseases like myocardial infarction, Timothy syndrome, dilated cardiomyopathy, Parkinson's, Alzheimer's and Huntington's disease. Despite the promising potential of iPSCs, genome contamination and low efficacy of cell reprogramming remain significant challenges.
Animal testing has shown unsatisfaction when it comes to examination of hepato-neuro-and cardiotoxicity, as well as in the development of new therapies, while use of in vitro model systems is limited by unavailability of human tissues. For this reason, use of human embryonic stem cells (hESC) as unlimited source for producing differentiated somatic progeny, represents a great medical advance. Induced pluripotent stem cells (iPSC) represent a new type of stem cells that occur by reprogramming of genomes of adult stem cells, such as dermal fibroblasts into a pluripotent state. These cells have many similarities with embryonic stem cells, and their reprogramming requests transcription factors OCT4, SOX2, and KLF4. IPSC are characterized by the ability of recovery and differentiation into different cell types such as-cells, hepatocytes, cardiomyocytes, hematopoietic cells, which opens the door to the new methods of treatment of many diseases especially in the field of personalized regenerative medicine. This paperwork contains future trends and possibilities of using iPSC's in regenerative personalized medicine, and with great certainty we can say that the discovery of the same has brought a revolutionary changes to medicine, and that these cells will soon be used not only for modeling of various diseases, but also for treating diseases and finding and testing new drugs that will help to improve the quality of life in many patients.
Induced pluripotent Stem Cells: Where we are currently?
Halo 194, 2020
Induced Pluripotent Stem Cells (iPSCs) are a type of pluripotent stem cells generated by reprogramming an adult somatic cell genome to the stage of a pluripotent stem cell in vitro by inducing a forced expression of specific transcription factors that are important for the maintenance of pluripotency. The iPSCs seem to be very similar to Embryonic Stem Cells (ESCs) in terms of morphology, cell surface markers and gene expression levels, but recent studies have demonstrated some differences between the two cell types. However, iPSCs might have potential application in regenerative medicine, transplantation, drug testing, disease modelling, and avoidance of tissue rejection and with less ethical concern than ESCs. This paper aims to present the most important characteristics of iPSCs which have therapeutic significance.
Frontiers in Cell and Developmental Biology, 2015
Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.
Induced pluripotent stem cells: A new technology to study human diseases
The International Journal of Biochemistry & Cell Biology, 2011
Induced pluripotent stem cells (iPS cells) are somatic cells that have been reprogrammed to a pluripotent state by the introduction of specific factors. They can be generated from cells of different origins such as fibroblasts, keratinocytes, hepatocytes and blood. iPS cells are similar to embryonic stem cells in several aspects such as morphology, expression of pluripotency markers and the capacity to develop teratomas; tumors containing cells of the three germ layers. As pluripotent stem cells they can be differentiated into several lineages including neuronal, cardiac and blood cells. Recently, several groups have successfully generated patient-specific iPS cells from donors suffering different disorders and differentiated them into the cell type affected by the disease. These new human cell-based models cannot only be used to study the dynamics of diseases but also as systems to screen new drugs. Moreover, iPS cells promise to be good candidates for regenerative medicine.
In‐a‐dish: Induced pluripotent stem cells as a novel model for human diseases
2013
Human pluripotent stem cells bring promise in regenerative medicine due to their selfrenewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab. ' 2012 International Society for Advancement of Cytometry Key terms induced pluripotent stem cell; disease modeling; reprogramming; neurological diseases PLURIPOTENCY Pluripotency is generally defined by the ability of a stem cell to differentiate into cell types representative of all three germ layers: ectoderm, mesoderm, and endoderm (1). Pluripotent stem cells are found in the inner cell mass of a blastocyst during embryogenesis, after the process of fertilization. It is also possible to generate a blastocyst in vitro, without going through the process of fertilization by the meeting of two gametes. In 1962, John Gurdon was the first to report the reprogramming of fully differentiated intestinal epithelial cells from Xenopus tadpoles by transferring the nucleus of the somatic cells into Xenopus oocytes and obtaining a blastocyst in vitro (2). However, it took more than 30 years until in 1996, Ian Wilmut demonstrated that a somatic cell nucleus from a mammal could similarly be reprogrammed through transfer to an enucleated oocyte (3). Despite the success of Gurdon's method, this procedure was not very efficient for generating human pluripotent stem cells. The discovery of reprogramming by somatic cell nuclear transfer, together with advances in the culture of pluripotent murine and human embryonic stem cells, has led to a further understanding of the processes of self-renewal and differentiation (4,5). Generation of Induced Pluripotent Stem Cells from Human Somatic Cells Takahashi and Yamanaka pioneered a method of inducing somatic cells back to the embryonic stage, creating embryonic (ES)-like cells. These cells are called induced pluripotent stem cells (iPSC) (4). For this purpose they used the ectopic expression of 4 transcription factors: Oct-4 (octamer-binding transcription factor 4, also known as POU5F1), Sox-2 (Sex determining region Y box-2), Klf-4 (Kruppel-like factor 4), and c-Myc (proto-oncogene c-Myc). Oct-4 is a transcription factor initially active in the oocyte and it remains active in embryos throughout the preimplantation period (6). The Oct-4 gene expression is equated with an undifferentiated phenotype in normal as well as malignant tissue (7).
Human Induced Pluripotent Stem Cells: The Past, Present, and Future
Clinical Pharmacology & Therapeutics, 2011
A major breakthrough in the past 5 years is the development of the ability to reprogram somatic cells to pluripotency. It has rejuvenated the field of stem cell research, providing regenerative medicine with new possibilities. In this paper, we discuss the progress made in the reprogramming field with focus on induction methodologies, the use of induced pluripotent stem cells (iPSCs) for drug discovery, and issues and precautions related to their use in regenerative medicine.Clinical Pharmacology & Therapeutics (2011) 89 5, 741–745. doi:10.1038/clpt.2011.37
The promise of induced pluripotent stem cells in research and therapy
Nature, 2012
The field of stem-cell biology has been catapulted forward by the startling development of reprogramming technology. The ability to restore pluripotency to somatic cells through the ectopic co-expression of reprogramming factors has created powerful new opportunities for modelling human diseases and offers hope for personalized regenerative cell therapies. While the field is racing ahead, some researchers are pausing to evaluate whether induced pluripotent stem cells are indeed the true equivalents of embryonic stem cells and whether subtle differences between these cells might affect their research applications and therapeutic potential.