Induced pluripotent stem cells (iPSCs) are artificial stem cells that have been reprogrammed to a state of embryonic stem-cells by being forced to express factors and genes significant for retaining the defining embryonic stem cells properties. Direct reprogramming enable pluripotent stem cell lines from any somatic tissues as well as mammalian species to avoid the ethical issues that are associated with embryonic stem cells. Even though direct programming is technically simple, it is a technically slow and inefficient process because it is affected by different variables that impact its reproducibility, efficiency as well as quality of resulting iPSCs. Reprogramming of iPS cells can be categorized into two classes.
The first class involves exogenous genetic material integration and the other one does not involve genetic modification of donor cells. The adult cells are genetically induced to return to iPSCs through utilization of four significant factors of transcription that include Oct ¾, c-Myc, Klf4 and Sox2 ( Galkowska, Wojewodzka & Olszewski, 2016 ). The use of the integrative reprogramming techniques produces heterogeneous iPSC lines which hinder comparative analysis between lines. This problem has been solved by the use of Cre-detectable vectors. The other technique that is used to reprogram the iPSC is non-integrative reprogramming systems. Non-integrative reprogramming systems such as the newly published RNA-based technique are promising in terms of the high efficiency it achieves. Even though it is appealing, the high dosages of reprogramming factors result from direct messenger RNA delivery.
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As much as the combination of these is the most conventional way of generating the induced pluripotent stem cells, each of these factors can be replaced different related transcription factors such as small molecules, miRNAs or non-related genes like lineage specifiers. The reprogramming gene source can be produced from different origins including keratinocytes, neuronal progenitor cells, kidneys as well as adrenal glands. The two types of cells fusion can convert particular cell types from one form to another. In most cases, the reprogramming of the iPS cell technology relies on the cell lines sources. Pluripotent stem cells are promising in the regenerative medicine field because they can propagate endlessly and give rise to every other cell type in the body. Relying on the type of the donor cell, reprogramming can be achieved with different kinetics and efficiencies. The differences are contributed by variations in the endogenous levels of reprogramming factors, intrinsic epigenetic states and differentiation status. The various factors foster reprogramming, including genes that are expressed in early development, factors that influence cell proliferation or microRNAs.
There are various differences between induced pluripotent and embryonic stem cells. As much as they are different from each other, the two stem cells hold significant promise for medical applications and biomedical studies. To start with, embryotic stem cells are types of pluripotent stem cells that are obtained from the extensive inner cell of the pre-implantation embryos and present a critical tool for regenerative medicine and further serve as embryonic development models in vitro. They can segment themselves continuously in vitro while retaining the ability to produce all adult organism cell types. The distinct appearance of embryonic stem cells is made up of a series of transcriptional and epigenetic factors. The ESCs epigenetic status features are an open chromatin structure with DNA modification profiles and characteristic histone. In most cases, somatic cells obtain the embryonic stem cells through nuclear programming.
The three techniques that are involved include cell fusion, somatic cell nuclear transfer and defined transcription factors initiation which has been developed to reprogram somatic cells to pluripotency. Besides, the ESCs pluripotent state is enforced by epigenetic factors that are closely connected to the network of the pluripotency transcription factor. Resetting the somatic cells epigenetic state to ESCs is the ultimate tasks that can reprogram factors in iPSC production. On the other hand, IPS cells are produced by the somatic cells reprogramming following specific transcription factors exogenous expression such as SOX2, Oct ¾, KLF4 as well as c-Myc. The c-Myc has the ability of recreating the somatic cells into iPSCs ( King & Perrin, 2014 ). iPSCs are highly to ESCs in terms of global chromatin configuration, transcription program and chromatin modifications profiles. In terms of function, some of the iPSCs have developmental potential that resemble that of the ESCs.
Additionally, both embryonic and induced pluripotent stem cells are featured by the ability to undergo sustainable self-renewal when cultured with development factors offered by defined culture media and feeder cells. The phenotypes of pluripotent stem cells can be modulated by small bioactive molecules as well as chemical compounds that improve proliferation or direct pluripotent stem cells differentiation.
Potential therapies use stem cells to cure or prevent a disease. One of the potential therapies that use stem cells is hematopoietic stem cell transplantation (HSCT). The HSCT is utilized to cure individuals with diseases such as lymphoma and leukaemia. This is the lone extensively drilled kind of foundational microorganism treatment. Most creating cells are demolished by cytotoxic cells during chemotherapy. In any case, these specialists cannot segregate neoplastic cells from hematopoietic stem cells within the bone marrow. The inability to differentiate neoplastic cells or hematopoietic stem cells is the side effects that come from the traditional chemotherapy techniques that the stem cell attempt to reverse. In this case, the bone marrow of a healthy donor reintroduces the functional stem cells and replaces the cells that are lost in the body of the host during treatment. The transplanted cells then produce an immune response that kills the cancer cell.
Another potential therapy that uses stem cell is prochymal. Prochymal was conditionally approved in 2012 to manage the acute infections in children that do not respond to particular steroids. Nonetheless, prochymal is a stem treatment that relies upon mesenchymal undifferentiated cells got from the grown-up donor bone marrow. The MSCs are sanitized from the marrow, refined and bundled with more than 10,000 dosages acquired from a solitary donor. The FDA has additionally endorsed more than five hematopoietic undifferentiated cell items acquired from umbilical-cord blood for blood treatment and immunological sicknesses ( Müller & Lengerke, 2019 ). Likewise, the European Medicines Agency suggested limbal undifferentiated organisms in 2014 for people with intense limbal undeveloped cell lack because of eye burns.
The iPSCs has numerous advantages. The advantages of the iPSCs are that it avoid the use of human embryo, has the capability induce stem cell and is a new promises to the cellular therapy. Additionally, the iPSCs has the possibility of studying several diseases such as cancer. Even though the iPSCs has numerous advantages, it also has disadvantages. The main advantage of using iPSCs is that they are associated with cancer. More particularly, the DNA of retroviruses is inserted in the genome which triggers the gene expression that causes. The c-Myc, a gene that is utilized in reprogramming notably known as oncogene can also cause cancer. In non-dividing cell types, the reprogramming somatic cells rate to iPSCs is low. Therefore, there is need to examine the variability and quality of the reprogramming process. For instance, iPSCs always have a tendency not to completely differentiate.
The ethical concern of induced pluripotent stem cells is that they should not be utilized to create germ cells, develop human embryos or clone people. In order to conduct this, the patient in stem cell therapy should give out the consent.
References
Galkowska, H., Wojewodzka, U., & Olszewski, W. L. (2016). Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair and Regeneration , 14 (5), 558-565.
King, N. M., & Perrin, J. (2014). Ethical issues in stem cell research and therapy. Stem Cell Research & Therapy , 5 (4), 85.
Müller, R., & Lengerke, C. (2019). Patient-specific pluripotent stem cells: promises and challenges. Nature Reviews Endocrinology , 5 (4), 195.
