Induced Pluripotent Stem Cells (I Psc) Research Papers (original) (raw)

Induced Pluripotent Stem Cells (iPSCs) are self renewable and can differentiate to different types of adult cells, which has shown great promises in the field of regenerative medicine. iPSCs are reprogrammed from human somatic cells... more

Induced Pluripotent Stem Cells (iPSCs) are self renewable and can differentiate to different types of adult cells, which has shown great promises in the field of regenerative medicine. iPSCs are reprogrammed from human somatic cells through ectopic expression of various transcription factors viz. Oct4, Sox2, Klf4, and c-Myc (OSKM). This novel technology enables derivation of patient specific cells, which possess a potential cure for many diseases. During the last decade, significant progresses have been achieved in enhancing the reprogramming efficiency, safety of iPSCs derivation, development of different delivery techniques by various research groups. Nevertheless, it is important to resolve and define the mechanism underlying the pluripotent stem cells. Major bottleneck which arises during iPSCs generation is the availability of source material (cells/tissues), difficulty to deliver transcription factors with no aberrant genetic modifications and limited reprogramming efficiency. Reprogramming may be achieved by employing different cocktails with number of different transcription factors, application of miRNA and some small molecules such as (Valproic acid, CHiR99021, Sodium butyrate, Vitamin C, Parnate etc). Similarly, various starting source materials have been demonstrated for iPSC based therapies including fibroblasts, cord blood, peripheral blood, keritinocytes, urine, etc., with their specific uses and limitations. Moreover, with the advent of many new reprogramming techniques, various direct delivery methods have been introduced such as using synthetic mRNA expressing pluripotent gene network has been shown to be an appropriate technique to deliver transcription factors and a dozen of small molecules which can replace transcription factors or enhance reprogramming efficiency. This article addresses the iPSCs technology mechanisms, progresses and current perspectives in the field.

Gene transfer into haematopoietic stem cells (HSCs) has now come to the stage where it can be recognized as a form of established therapy for patients with a certain range of genetic diseases. Primary immunodeficiency disease (PID)... more

Gene transfer into haematopoietic stem cells (HSCs) has now come to the stage where it can be recognized as a form of established therapy for patients with a certain range of genetic diseases. Primary immunodeficiency disease (PID) represents an ideal pathological target for this type of genetic medicine, that is HSC gene therapy, as exemplified well by the successful cases with adenosine-deami-nase (ADA) deficiency. Other diseases including X-linked severe combined immu-nodeficiency disease (X-SCID), chronic granulomatous disease (CGD) and Wiskott–Aldrich syndrome (WAS) have also been the targets of gene therapy, but the efficacy reportedly varies considerably. In addition, all those diseases except ADA deficiency have been demonstrated to be subject to an inherent risk of insertional leukaemogenesis as long as gene transfer accompanies genomic insertion. Researchers therefore should continue to aim for further improvement of HSC gene therapy to maximize both safety and efficacy. To achieve this aim, an ideal model system is desired, by which faithful recapitulation of the disease-related pathophysiology is feasible. Recently, a new model system possibly constituting such an ideal platform has come to reality; that is, patient-/disease-specific induced pluripotent stem cells (iPSCs). iPSCs should particularly be useful for modelling genetic disorders, because of their excellent potential to differentiate into any types of somatic cells while retaining the patient-specific genetic mutations. These model cells should allow testing various kinds of genetic manipulation and also detailed analysis of the target cells before/after differentiation , thus providing a disease-specific platform for preclinical studies to test safety and efficacy of each gene-modification procedure.

Stem cells are unspecialized cells that develop into the specialized cells that make up the different types of tissue in the human body.They are characterized by the ability to renew themselves through mitotic... more

Stem cells are unspecialized cells that develop into the specialized
cells that make up the different types of tissue in the human
body.They are characterized by the ability to renew themselves
through mitotic cell division and differentiating into a diverse range
of specialized cell types. They are vital to the development, growth,
maintenance, and repair of our brains, bones, muscles, nerves, blood,
skin, and other organs .Stem cells are found in all of us, from the
early stages of human development to the end of life. Stem cell
research holds tremendous promise for the development of novel
therapies for many serious diseases and injuries. While stem cellbased treatments have been established as a clinical standard of care
for some conditions, such as hematopoietic stem cell transplants for
leukemia and epithelial stem cell-based treatments for burns and
corneal disorders, the scope of potential stem cell-based therapies has
expanded in recent years due to advances in stem cell research. It has
been only recently that scientists have understood stem cells well
enough to consider the possibilities of growing them outside the body
for long periods of time. With that advance, rigorous experiments can
be conducted, and the possibility of manipulating these cells in such a
way that specific tissues can be grown is real.

Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both... more

Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods.

Stem cells interact with and respond to a myriad of signals emanating from their extracellular microenvironment. The ability to harness the regenerative potential of stem cells via a synthetic matrix has promising implications for... more

Stem cells interact with and respond to a myriad of signals emanating from their extracellular microenvironment. The ability to harness the regenerative potential of stem cells via a synthetic matrix has promising implications for regenerative medicine. Electrospun fibrous scaffolds can be prepared with high degree of control over their structure creating highly porous meshes of ultrafine fibers that resemble the extracellular matrix topography, and are amenable to various functional modifications targeted towards enhancing stem cell survival and proliferation, directing specific stem cell fates, or promoting tissue organization. The feasibility of using such a scaffold platform to present integrated topographical and biochemical signals that are essential to stem cell manipulation has been demonstrated. Future application of this versatile scaffold platform to human embryonic and induced pluripotent stem cells for functional tissue repair and regeneration will further expand its potential for regenerative therapies.

To provide a comprehensive source of information about the reprogramming process and induced pluripotency. The ability of stem cells to renew their own population and to differentiate into specialized cell types has always attracted... more

To provide a comprehensive source of information about the reprogramming process and induced pluripotency. The ability of stem cells to renew their own population and to differentiate into specialized cell types has always attracted researchers looking to exploit this potential for cellular replacement therapies, pharmaceutical testing and studying developmental pathways. While adult stem cell therapy has already been brought to the clinic, embryonic stem cell research has been beset with legal and ethical impediments. The conversion of human somatic cells to human induced pluripotent stem cells (hiPSCs), which are equivalent to human embryonic stem cells (hESCs), provides a system to sidestep these barriers and expedite pluripotent stem cell research for the aforementioned purposes. However, being a very recent discovery, iPSCs have yet to overcome many other obstacles and criticism to be proven safe and feasible for clinical use. This review introduces iPSC, the various methods th...

A “right to withdraw” from research participation is an important mechanism for ensuring voluntariness and respecting participant autonomy throughout a study. This right often is expressed as an absolute, dictating that a participant can... more

A “right to withdraw” from research participation is an important mechanism
for ensuring voluntariness and respecting participant autonomy throughout a study. This right
often is expressed as an absolute, dictating that a participant can withdraw from research
at any time for any reason. However, it is more challenging to define a right to withdraw
when the interactions between a researcher and participant have ended but the researcher is
continuing to use biospecimens provided by the research participant. This issue is becoming
particularly complicated as researchers are generating induced pluripotent stem cell (iPSC)
lines for a broad spectrum of research applications, banking, distribution, commercial product
development, drug screening, and preclinical testing for cell-based therapies. The generation
of iPSCs from biospecimens presents particular challenges for informed consent and the right
to withdraw as researchers develop informed consent documents and as projects undergo ethics
review. Here we consider the reasons why a participant may want to withdraw donated
biospecimens from research, especially when considering the ethical landscape of withdrawal
from iPSC research in particular. We then suggest guidance to help policy makers and ethics
review bodies evaluate the issue of withdrawal in relation to iPSC research.

Recent Progress in pluripotent stem cell biology has nourished the hope to use for brain repair stem cell based therapy. Cell reprogramming diseases models seems particularly hopeful in the field of human neurological disorders including... more

Recent Progress in pluripotent stem cell biology has nourished the hope to use for brain repair stem cell based therapy. Cell reprogramming diseases models seems particularly hopeful in the field of human neurological disorders including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, for which animal models could be not enough inclusive for describing all aspects of disease pathology. In addition, to improve specific subtype neural differentiation developments aimed at reprogramming technology have been made. Brain repair issue, recognized the induced pluripotent stem cells as the most significant space of intervention because of the high rate expansion, as a cell source in transplantation and cellular therapy. It possess attractive features, including the capacity for large-scale expansion as a cell source for neural transplantation, procedures and potential for differentiation into a range of potentially therapeutic cell types relevant for specific neurological conditions. While collecting iPSC we obtain a unique and well characterized source to clarify disease mechanisms. Such a procedure represents a human stem cell platform for discovering potential drugs as well as new opportunities for mechanistic studies. In this review, we introduce iPSC-based disease modeling to be applied in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the... more

Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the functional evaluation of the genetic alteration has been carried out by expressing the mutated proteins in in-vitro heterologous systems. While these studies have provided a wealth of functional details that have greatly enhanced the understanding of the pathological mechanisms, it has always been clear that heterologous expression of the mutant protein bears the intrinsic limitation of the lack of a proper intracellular environment and the lack of pathological remodeling. The results obtained from the application of the next generation sequencing technique to patients suffering from cardiac diseases have identified several loci, mostly in non-coding DNA regions, which still await functional analysis. The isolation and culture of human embryonic stem cells...

The pinnacle of four decades of research, induced pluripotent stem cells (iPSCs), and genome editing with the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR) now promise to take drug development and... more

The pinnacle of four decades of research, induced pluripotent stem cells (iPSCs), and genome editing with the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR) now promise to take drug development and regenerative medicine to new levels and to enable the interrogation of disease mechanisms with a hitherto unimaginable level of model fidelity. Autumn 2014 witnessed the first patient receiving iPSCs differentiated into retinal pigmented ep-ithelium to treat macular degeneration. Technologies such as 3D bioprinting may now exploit these advances to manufacture organs in a dish. As enticing as these prospects are, these technologies demand a deeper understanding, which will lead to improvements in their safety and efficacy. For example, precise and more efficient reprogramming for iPSC production is a requisite for wider clinical adoption. Improving awareness of the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) and genomic epigenetic status will contribute to the achievement of these aims. Similarly, increased efficiency, avoidance of off-target effects, and expansion of available target sequences are critical to the uptake of genome editing technology. In this review, we survey the historical development of genetic manipulation and stem cells. We explore the potential of genetic manipulation of iPSCs for in vitro disease modeling, generation of new animal models, and clinical applicability. We highlight the aspects that define CRISPR-Cas as a breakthrough technology, look at gene correction , and consider some important ethical and societal implications of this approach.

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology,... more

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

The induction of pluripotency in somatic cells is widely considered as a major breakthrough in regenerative medicine, because this approach provides the basis for individualized stem cell-based therapies. Moreover, with respect to cell... more

The induction of pluripotency in somatic cells is widely considered as a major breakthrough in regenerative medicine, because this approach provides the basis for individualized stem cell-based therapies. Moreover, with respect to cell transplantation and tissue engineering, expertise from bioengineering to transplantation medicine is now meeting basic research of stem cell biology.In this chapter, we discuss techniques, potential and possible risks of induced pluripotent stem (iPS) cells in the light of needs for patient-derived pluripotent stem cells. To this end, we compare these cells with other sources of pluripotent cells and discuss the first encouraging results of iPS cells in pharmacological research, disease modeling and cell transplantation, providing fascinating perspectives for future developments in biotechnology and regenerative medicine.