scholarly journals Revolution in Gene Medicine Therapy and Genome Surgery

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 575 ◽  
Author(s):  
David J. Jiang ◽  
Christine L. Xu ◽  
Stephen H. Tsang
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Viral Vectors ◽  
The Body ◽  
Inherited Disorders ◽  
Promising Alternative ◽  
Target Gene Therapy ◽  
Induced Pluripotent ◽  
Surgical Treatments

Recently, there have been revolutions in the development of both gene medicine therapy and genome surgical treatments for inherited disorders. Much of this progress has been centered on hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple adeno-associated virus (AAV) vectors. CRISPR/Cas9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. Newer CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo-derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine Food and Drug Administration (FDA) treatment trials.

scholarly journals Revolution in Gene Medicine Therapy and Genome Therapy

2018 ◽  
Author(s):  
David Jiang ◽  
Christine L. Xu ◽  
Stephen H. Tsang
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Viral Vectors ◽  
The Body ◽  
Promising Alternative ◽  
Retinal Dystrophies ◽  
Target Gene Therapy ◽  
Induced Pluripotent ◽  
Surgical Treatments

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

scholarly journals Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

2021 ◽  
Author(s):  
Aida Nourbakhsh ◽  
Brett M. Colbert ◽  
Eric Nisenbaum ◽  
Aziz El-Amraoui ◽  
Derek M. Dykxhoorn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Hearing Loss ◽  
Treatment Modalities ◽  
Versus Gene ◽  
Vitro Model ◽  
New Treatment ◽  
Induced Pluripotent ◽  
Therapy Strategies

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

scholarly journals Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 6124
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rocío Castro-Viñuelas ◽  
María Piñeiro-Ramil ◽  
Silvia Rodríguez-Fernández ◽  
Isaac Fuentes-Boquete ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Musculoskeletal Diseases ◽  
The Body ◽  
Cellular Mechanisms ◽  
Induced Pluripotent ◽  
New Strategies

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.

scholarly journals Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models

2021 ◽  
Vol 8 ◽  
Author(s):  
Crystal C. Kennedy ◽  
Erin E. Brown ◽  
Nadia O. Abutaleb ◽  
George A. Truskey
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Organ Systems ◽  
Temporal Waveform ◽  
Induced Pluripotent

The vascular endothelium is present in all organs and blood vessels, facilitates the exchange of nutrients and waste throughout different organ systems in the body, and sets the tone for healthy vessel function. Mechanosensitive in nature, the endothelium responds to the magnitude and temporal waveform of shear stress in the vessels. Endothelial dysfunction can lead to atherosclerosis and other diseases. Modeling endothelial function and dysfunction in organ systems in vitro, such as the blood–brain barrier and tissue-engineered blood vessels, requires sourcing endothelial cells (ECs) for these biomedical engineering applications. It can be difficult to source primary, easily renewable ECs that possess the function or dysfunction in question. In contrast, human pluripotent stem cells (hPSCs) can be sourced from donors of interest and renewed almost indefinitely. In this review, we highlight how knowledge of vascular EC development in vivo is used to differentiate induced pluripotent stem cells (iPSC) into ECs. We then describe how iPSC-derived ECs are being used currently in in vitro models of organ function and disease and in vivo applications.

scholarly journals Differentiation of human induced pluripotent stem cells into erythroid cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohsen Ebrahimi ◽  
Mehdi Forouzesh ◽  
Setareh Raoufi ◽  
Mohammad Ramazii ◽  
Farhoodeh Ghaedrahmati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Promising Alternative ◽  
Human Ipscs ◽  
Induced Pluripotent ◽  
Human Ipsc

AbstractDuring the last years, several strategies have been made to obtain mature erythrocytes or red blood cells (RBC) from the bone marrow or umbilical cord blood (UCB). However, UCB-derived hematopoietic stem cells (HSC) are a limited source and in vitro large-scale expansion of RBC from HSC remains problematic. One promising alternative can be human pluripotent stem cells (PSCs) that provide an unlimited source of cells. Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are self-renewing progenitors that can be differentiated to lineages of ectoderm, mesoderm, and endoderm. Several previous studies have revealed that human ESCs can differentiate into functional oxygen-carrying erythrocytes; however, the ex vivo expansion of human ESC-derived RBC is subjected to ethical concerns. Human iPSCs can be a suitable therapeutic choice for the in vitro/ex vivo manufacture of RBCs. Reprogramming of human somatic cells through the ectopic expression of the transcription factors (OCT4, SOX2, KLF4, c-MYC, LIN28, and NANOG) has provided a new avenue for disease modeling and regenerative medicine. Various techniques have been developed to generate enucleated RBCs from human iPSCs. The in vitro production of human iPSC-derived RBCs can be an alternative treatment option for patients with blood disorders. In this review, we focused on the generation of human iPSC-derived erythrocytes to present an overview of the current status and applications of this field.

scholarly journals Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage

2018 ◽  
Vol 19 (9) ◽  
pp. 2788 ◽  
Author(s):  
Guang Yang ◽  
Hyenjong Hong ◽  
April Torres ◽  
Kristen Malloy ◽  
Gourav Choudhury ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
In Vitro Models ◽  
The Body ◽  
Model Systems ◽  
Induced Pluripotent

Humans and nonhuman primates (NHP) are similar in behavior and in physiology, specifically the structure, function, and complexity of the immune system. Thus, NHP models are desirable for pathophysiology and pharmacology/toxicology studies. Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable transformative developmental, translational, or evolutionary studies in a field of inquiry currently hampered by the limited availability of research specimens. NHP-iPSCs may address specific questions that can be studied back and forth between in vitro cellular assays and in vivo experimentations, an investigational process that in most cases cannot be performed on humans because of safety and ethical issues. The use of NHP model systems and cell specific in vitro models is evolving with iPSC-based three-dimensional (3D) cell culture systems and organoids, which may offer reliable in vitro models and reduce the number of animals used in experimental research. IPSCs have the potential to give rise to defined cell types of any organ of the body. However, standards for deriving defined and validated NHP iPSCs are missing. Standards for deriving high-quality iPSC cell lines promote rigorous and replicable scientific research and likewise, validated cell lines reduce variability and discrepancies in results between laboratories. We have derived and validated NHP iPSC lines by confirming their pluripotency and propensity to differentiate into all three germ layers (ectoderm, mesoderm, and endoderm) according to standards and measurable limits for a set of marker genes. The iPSC lines were characterized for their potential to generate neural stem cells and to differentiate into dopaminergic neurons. These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a unique niche in comparative genomics to understand gene regulatory principles underlying emergence of human traits, in infectious disease pathogenesis, in vaccine development, and in immunological barriers in regenerative medicine.

Regenerative Medicine: Which Cells?

2021 ◽  
Author(s):  
Raymond Ardaillou
Keyword(s):  
Stem Cells ◽  
Mass Production ◽  
Genetic Diseases ◽  
The Body ◽  
Major Step ◽  
Hematopoietic Stem ◽  
Blastocyst Complementation ◽  
Cell Organization ◽  
Induced Pluripotent

Stem cells used in therapy include mainly hematopoietic stem cells (HSC) to treat aplasias, leukemias and hematological genetic diseases, and mesenchymal stem cells (MSC) produced in small quantities by the bone marrow, but also other tissues, to treat cardiac and cutaneous diseases thanks to their secretory properties of growth factors. A major step was taken with the use of embryonic (ESC) or induced pluripotent stem cells (iPS). The former are used, after isolation and differentiation, either in rare therapeutic purposes or for the in vitro screening of drugs. iPS are produced from adult cells after reprogramming and differentiation and utilized for the treatment of various diseases in autologous or allogeneic form, the second condition allowing only mass production. New lines of research are now in progress including the creation of organoids that are templates of many organs of the body and allow the process of cell organization and its perturbations to be analyzed. Creation of post-meiosis gametes (23 chromosomes) from iPS or ESC is intended to treat serious genetic diseases. Creation of human chimera by interspecies blastocyst complementation has also been studied in view of organ transplantation. It is only allowed for the implantation of human cells in animal blastocysts and prohibited for the reverse. Implantation in uterus of the modified embryos is prohibited by the French law.

Mesenchymal Stem Cells: A New Generation of Therapeutic Agents as Vehicles in Gene Therapy

2020 ◽  
Vol 20 (4) ◽  
pp. 269-284
Author(s):  
Mahmoud Gharbavi ◽  
Ali Sharafi ◽  
Saeed Ghanbarzadeh
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Therapeutic Agents ◽  
Targeted Gene Delivery ◽  
The Status

In recent years, mesenchymal stem cells (MSCs) as a new tool for therapeutic gene delivery in clinics have attracted much attention. Their advantages cover longer lifespan, better isolation, and higher transfection efficiency and proliferation rate. MSCs are the preferred approach for cell-based therapies because of their in vitro self-renewal capacity, migrating especially to tumor tissues, as well as anti-inflammatory and immunomodulatory properties. Therefore, they have considerable efficiency in genetic engineering for future clinical applications in cancer gene therapy and other diseases. For improving therapeutic efficiency, targeted therapy of cancers can be achieved through the sustained release of therapeutic agents and functional gene expression induction to the intended tissues. The development of a new vector in gene therapy can improve the durability of a transgene expression. Also, the safety of the vector, if administered systemically, may resolve several problems, such as durability of expression and the host immune response. Currently, MSCs are prominent candidates as cell vehicles for both preclinical and clinical trials due to the secretion of therapeutic agents in several cancers. In the present study, we discuss the status of gene therapy in both viral and non-viral vectors along with their limitations. Throughout this study, the use of several nano-carriers for gene therapy is also investigated. Finally, we critically discuss the promising advantages of MSCs in targeted gene delivery, tumor inhibition and their utilization as the gene carriers in clinical situations.

scholarly journals Potential Clinical Applications for Human Pluripotent Stem Cell-Derived Blood Components

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Erin A. Kimbrel ◽  
Shi-Jiang Lu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Large Scale ◽  
Embryonic Stem ◽  
Adult Stem Cell ◽  
Cell Types ◽  
The Body ◽  
Blood Components ◽  
Induced Pluripotent

The ability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to divide indefinitely without losing pluripotency and to theoretically differentiate into any cell type in the body makes them highly attractive cell sources for large scale regenerative medicine purposes. The current use of adult stem cell-derived products in hematologic intervention sets an important precedent and provides a guide for developing hESC/iPSC based therapies for the blood system. In this review, we highlight biological functions of mature cells of the blood, clinical conditions requiring the transfusion or stimulation of these cells, and the potential for hESC/iPSC-derivatives to serve as functional replacements. Many researchers have already been able to differentiate hESCs and/or iPSCs into specific mature blood cell types. For example, hESC-derived red blood cells and platelets are functional in tasks such as oxygen delivery and blood clotting, respectively and may be able to serve as substitutes for their donor-derived counterparts in emergencies. hESC-derived dendritic cells are functional in antigen-presentation and may be used as off-the-shelf vaccine therapies to stimulate antigen-specific immune responses against cancer cells. However,in vitrodifferentiation systems used to generate these cells will need further optimization before hESC/iPSC-derived blood components can be used clinically.

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