Recent Updates on Induced Pluripotent Stem Cells in Hematological Disorders

Over the past decade, enormous progress has been made in the field of induced pluripotent stem cells (iPSCs). Patients’ somatic cells such as skin fibroblasts or blood cells can be used to generate disease-specific pluripotent stem cells, which have unlimited proliferation and can differentiate into all cell types of the body. Human iPSCs offer great promises and opportunities for treatments of degenerative diseases and studying disease pathology and drug screening. So far, many iPSC-derived disease models have led to the discovery of novel pathological mechanisms as well as new drugs in the pipeline that have been tested in the iPSC-derived cells for efficacy and potential toxicities. Furthermore, recent advances in genome editing technology in combination with the iPSC technology have provided a versatile platform for studying stem cell biology and regenerative medicine. In this review, an overview of iPSCs, patient-specific iPSCs for disease modeling and drug screening, applications of iPSCs and genome editing technology in hematological disorders, remaining challenges, and future perspectives of iPSCs in hematological diseases will be discussed.

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Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

Cardiology ◽

10.1159/000381280 ◽

2015 ◽

Vol 131 (4) ◽

pp. 236-244 ◽

Cited By ~ 1

Author(s):

Hong-jie Chi ◽

Song Gao ◽

Xin-chun Yang ◽

Jun Cai ◽

Wen-shu Zhao ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Clinical Application ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Disease Diagnosis ◽

The Body ◽

Patient Specific ◽

Human Ipscs ◽

Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

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Derivation of induced pluripotent stem cells from ferret somatic cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00456.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. L671-L683

Author(s):

Jinghui Gao ◽

Sophia Petraki ◽

Xingshen Sun ◽

Leonard A. Brooks ◽

Thomas J. Lynch ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Patient Specific ◽

Preclinical Model ◽

Specific Cell ◽

Chronic Lung Diseases ◽

Human Ipscs ◽

Fetal Fibroblasts ◽

Induced Pluripotent

Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung, where ferrets provide an attractive mammalian model of both acute and chronic lung diseases, such as influenza, cystic fibrosis, A1A emphysema, and obliterative bronchiolitis, closely recapitulating disease pathogenesis, as it occurs in humans. As such, ferrets have the potential to be a valuable preclinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multilineage differentiation, and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.

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Nanomedicine-based Curcumin Approach Improved ROS Damage in Best Dystrophy-specific Induced Pluripotent Stem Cells

Cell Transplantation ◽

10.1177/0963689719860130 ◽

2019 ◽

Vol 28 (11) ◽

pp. 1345-1357 ◽

Cited By ~ 2

Author(s):

Tai-Chi Lin ◽

Yi-Ying Lin ◽

Chih-Chen Hsu ◽

Yi-Ping Yang ◽

Chang-Hao Yang ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Patient Specific ◽

Macular Dystrophy ◽

Junction Protein ◽

Induced Pluripotent

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.

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CRISPR/Cas9-mediated genome editing has demonstrated significant promise for genetic correction in autologous hematopoietic stem/progenitor cells (HSPCs) and induced pluripotent stem cells (iPSCs)

10.31219/osf.io/xk54r ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Induced Pluripotent Stem Cells ◽

Progenitor Cells ◽

Genome Editing ◽

Pluripotent Stem Cells ◽

Genetic Disorders ◽

Hematopoietic Stem ◽

Hematological Disorders ◽

Induced Pluripotent

According to current research, CRISPR/Cas9-mediated genome editing has shown enormous potential in the correction of genetic defects in autologous hematopoietic stem/progenitor cells (HSPCs) and induced pluripotent stem cells (iPSCs). Furthermore, the advancement of iPSC reprogramming technology as well as the CRISPR/Cas9 system has opened the door to new possibilities in the field of gene and cell therapy combinations. Despite the fact that there are a number of technological obstacles to overcome, CRISPR/Cas9 remains a promising therapeutic method with a great deal of potential for future gene therapy applications. Early success in treating hereditary hematological disorders opens the door to new options for treating other genetic disorders and constitutes a significant step forward in the development of gene therapy.

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Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development

Physiological Reviews ◽

10.1152/physrev.00039.2017 ◽

2019 ◽

Vol 99 (1) ◽

pp. 79-114 ◽

Cited By ~ 43

Author(s):

Peter Karagiannis ◽

Kazutoshi Takahashi ◽

Megumu Saito ◽

Yoshinori Yoshida ◽

Keisuke Okita ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Molecular Mechanism ◽

Pluripotent Stem Cells ◽

Ectopic Expression ◽

Developmental State ◽

The Body ◽

Human Ipscs ◽

Wide Range ◽

Induced Pluripotent

The discovery of somatic cell nuclear transfer proved that somatic cells can carry the same genetic code as the zygote, and that activating parts of this code are sufficient to reprogram the cell to an early developmental state. The discovery of induced pluripotent stem cells (iPSCs) nearly half a century later provided a molecular mechanism for the reprogramming. The initial creation of iPSCs was accomplished by the ectopic expression of four specific genes (OCT4, KLF4, SOX2, and c-Myc; OSKM). iPSCs have since been acquired from a wide range of cell types and a wide range of species, suggesting a universal molecular mechanism. Furthermore, cells have been reprogrammed to iPSCs using a myriad of methods, although OSKM remains the gold standard. The sources for iPSCs are abundant compared with those for other pluripotent stem cells; thus the use of iPSCs to model the development of tissues, organs, and other systems of the body is increasing. iPSCs also, through the reprogramming of patient samples, are being used to model diseases. Moreover, in the 10 years since the first report, human iPSCs are already the basis for new cell therapies and drug discovery that have reached clinical application. In this review, we examine the generation of iPSCs and their application to disease and development.

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Patient-Specific Induced Pluripotent Stem Cells for SOD1-Associated Amyotrophic Lateral Sclerosis Pathogenesis Studies

Acta Naturae ◽

10.32607/20758251-2014-6-1-54-60 ◽

2014 ◽

Vol 6 (1) ◽

pp. 54-60 ◽

Cited By ~ 26

Author(s):

I. V. Chestkov ◽

E. A. Vasilieva ◽

S. N. Illarioshkin ◽

M. A. Lagarkova ◽

S. L. Kiselev

Keyword(s):

Stem Cells ◽

Amyotrophic Lateral Sclerosis ◽

Induced Pluripotent Stem Cells ◽

Motor Neurons ◽

Pluripotent Stem Cells ◽

Ips Cells ◽

The Body ◽

Patient Specific ◽

Induced Pluripotent ◽

Lateral Sclerosis

The genetic reprogramming technology allows one to generate pluripotent stem cells for individual patients. These cells, called induced pluripotent stem cells (iPSCs), can be an unlimited source of specialized cell types for the body. Thus, autologous somatic cell replacement therapy becomes possible, as well as the generation of in vitro cell models for studying the mechanisms of disease pathogenesis and drug discovery. Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder that leads to a loss of upper and lower motor neurons. About 10% of cases are genetically inherited, and the most common familial form of ALS is associated with mutations in the SOD1 gene. We used the reprogramming technology to generate induced pluripotent stem cells with patients with familial ALS. Patient-specific iPS cells were obtained by both integration and transgene-free delivery methods of reprogramming transcription factors. These iPS cells have the properties of pluripotent cells and are capable of direct differentiation into motor neurons.

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Abstract 2483: Generation of patient-specific and genome-edited MEN2A patient-derived induced pluripotent stem cells as novel tools for drug screening

10.1158/1538-7445.am2016-2483 ◽

2016 ◽

Author(s):

Julien Hadoux ◽

Christophe Desterke ◽

Olivier Féraud ◽

Mathieu Guibert ◽

Roberta Francesca De Rose ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Patient Specific ◽

Induced Pluripotent

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Induced Pluripotent Stem Cells as a Tool for Modeling Hematologic Disorders and as a Potential Source for Cell-Based Therapies

Cells ◽

10.3390/cells10113250 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3250

Author(s):

Ponthip Pratumkaew ◽

Surapol Issaragrisil ◽

Sudjit Luanpitpong

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Patient Specific ◽

Great Promise ◽

Hematologic Disorders ◽

Cell Based Therapy ◽

Induced Pluripotent

The breakthrough in human induced pluripotent stem cells (hiPSCs) has revolutionized the field of biomedical and pharmaceutical research and opened up vast opportunities for drug discovery and regenerative medicine, especially when combined with gene-editing technology. Numerous healthy and patient-derived hiPSCs for human disease modeling have been established, enabling mechanistic studies of pathogenesis, platforms for preclinical drug screening, and the development of novel therapeutic targets/approaches. Additionally, hiPSCs hold great promise for cell-based therapy, serving as an attractive cell source for generating stem/progenitor cells or functional differentiated cells for degenerative diseases, due to their unlimited proliferative capacity, pluripotency, and ethical acceptability. In this review, we provide an overview of hiPSCs and their utility in the study of hematologic disorders through hematopoietic differentiation. We highlight recent hereditary and acquired genetic hematologic disease modeling with patient-specific iPSCs, and discuss their applications as instrumental drug screening tools. The clinical applications of hiPSCs in cell-based therapy, including the next-generation cancer immunotherapy, are provided. Lastly, we discuss the current challenges that need to be addressed to fulfill the validity of hiPSC-based disease modeling and future perspectives of hiPSCs in the field of hematology.

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