Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications

Yoshihara, Masahito; Hayashizaki, Yoshihide; Murakawa, Yuji

doi:10.1007/s12015-016-9680-6

Cited by 206 publications

(140 citation statements)

References 119 publications

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“…When compared with ESCs, patient-specific iPSCs-derived cells were thought to provide significant advantages, such as the lack of ethical issues and immune response [221,241]. However, various studies described genomic instabilities in iPSC lines resulting either from pre-existing variations in parental adult cells or from mutations occurring during the reprogramming process and culturing time (summarized in: [242]). The unexpected finding that transplanted iPSC-derived cells possess immunogenic capabilities raised additional major concerns about the safety of iPSCs [243,244].…”

Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

161

136

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A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

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Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

161

136

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“…One of the biggest challenges, raising real safety concerns, is the genomic instability of hiPSCs, which became obvious particularly with the advance of highthroughput technologies such as next-generation sequencing [45].…”

Section: Human Induced Pluripotent Stem Cells (Hipscs)mentioning

confidence: 99%

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Gadjanski

2018

Osteochondral Tissue Engineering

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In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/ healing models and as in vitro models for drug toxicity/efficacy evaluation are covered. Highlights Biomimetic OC TE uses "smart" scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/ bone Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering Ivana GadjanskiAbstract In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue en...

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“…To date, there has been one trial attempt to treat exudative AMD using autologous iPSC-derived RPE cells [65,88,89,91,92]. In 2014, a Japanese woman with exudative macular degeneration was implanted with an iPSC-derived RPE sheet generated from her own fibroblasts [93]. Even though the first patient suffered “no serious adverse effects” of treatment, the trial has been put on hold due to the discovery of genetic mutations identified in the iPSCs that were to be used in a second patient in 2015 [94,95].…”

Section: Current Status Of Ipsc Therapies For the Treatment Of Retmentioning

confidence: 99%

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD)

Fields

Cai

Gong

et al. 2016

Cells

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The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

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Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications

Cited by 206 publications

References 119 publications

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD)

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