Ten years of induced pluripotency: from basic mechanisms to therapeutic applications

Karagiannis, Peter; Eto, Koji

doi:10.1242/dev.138172

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…The first iPSC lines were generated by genome integrating retroviruses, which involves risks of insertional mutagenesis, unwanted residual expression of exogenous genes, which can hamper differentiation, or spontaneous reactivation of foreign genes during differentiation [125] . Today iPSCs are reprogrammed with integration-free methods, for instance using RNA based methods [126] . iPSCs have certain advantages over hESC; they allow generation of patient- and disease-specific hiPSCs, and they do not face the same ethical, political, and religious issues related to human embryo use.…”

Section: Novel Disease-relevant Human Cell Modelsmentioning

confidence: 99%

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells

Cnop¹,

Toivonen²,

Igoillo-Esteve³

et al. 2017

Molecular Metabolism

213

179

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BackgroundPancreatic β cell dysfunction and death are central in the pathogenesis of most if not all forms of diabetes. Understanding the molecular mechanisms underlying β cell failure is important to develop β cell protective approaches.Scope of reviewHere we review the role of endoplasmic reticulum stress and dysregulated endoplasmic reticulum stress signaling in β cell failure in monogenic and polygenic forms of diabetes. There is substantial evidence for the presence of endoplasmic reticulum stress in β cells in type 1 and type 2 diabetes. Direct evidence for the importance of this stress response is provided by an increasing number of monogenic forms of diabetes. In particular, mutations in the PERK branch of the unfolded protein response provide insight into its importance for human β cell function and survival. The knowledge gained from different rodent models is reviewed. More disease- and patient-relevant models, using human induced pluripotent stem cells differentiated into β cells, will further advance our understanding of pathogenic mechanisms. Finally, we review the therapeutic modulation of endoplasmic reticulum stress and signaling in β cells.Major conclusionsPancreatic β cells are sensitive to excessive endoplasmic reticulum stress and dysregulated eIF2α phosphorylation, as indicated by transcriptome data, monogenic forms of diabetes and pharmacological studies. This should be taken into consideration when devising new therapeutic approaches for diabetes.

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Section: Novel Disease-relevant Human Cell Modelsmentioning

confidence: 99%

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells

Cnop¹,

Toivonen²,

Igoillo-Esteve³

et al. 2017

Molecular Metabolism

213

179

View full text Add to dashboard Cite

show abstract

“…However, it appears that the former strategy is very time consuming and quite costly as extensive quality control (such as entire genome sequencing) needs to be performed on each of the individual patient-specific iPSC lines owing to the elevated risk of generating random mutations, which could possibly lead to tumor formation during the iPSC generation protocol (Kamao et al, 2014). Homozygous HLA matched iPSC quality tested, banked and clinically safe cell lines from healthy donors (like those found at the CiRA Center, Kyoto University, Japan) also hold much promise for stem cell based therapies (Sugita et al, 2016; Takahashi and Yamanaka, 2016), but the current limited number of lines available makes this an option for only a small percent of the world's population (Karagiannis and Eto, 2016; Sakurai et al, 2016). In a recent interview, Shinya Yamanaka, who developed the strategy for iPSC generation (Takahashi and Yamanaka, 2006, 2016) suggested that iPSCs would likely only be useful for treating approximately nine human diseases (spinal cord injury, joint disorders, Parkinson's, specific blood disorders, heart and liver failure, retinal and corneal diseases, and diabetes) over the next decade or so, and IVD-related diseases were not among them (Ravven, 2017).…”

Section: Will Ipscs Play a Significant Role In Ivd Regenerationmentioning

confidence: 99%

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

Kraus

Lufkin

2017

Front. Cell Dev. Biol.

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The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 1013 cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches.

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“…Somatic cell reprogramming can be used to generate induced pluripotent stem (iPS) cells. Reprogramming is commonly achieved by overexpressing four transcription factors, Oct4, Sox2, Klf4 and c-Myc (referred to as the OSKM cocktail) (Takahashi and Yamanaka, 2006;Karagiannis and Eto, 2016). Other gene combinations have been used, such as the OSNL cocktail embryos, cESCs are able to participate in the formation of all the somatic tissues and product chimeric embryos.…”

Section: Re-capturing Avian Pluripotency In Vitromentioning

confidence: 99%

Pluripotency in avian species

Pain¹,

Kress²,

Rival‐Gervier³

2018

Int. J. Dev. Biol.

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Pluripotency defines the ability of a cell to self-renew and to differentiate into all embryonic lineages both in vitro and in vivo. This definition was first established mainly with the mouse model and the establishment of mouse embryonic stem cells (ESCs) in the 1980's and extended later on to other species including non-human primates and humans. Similarly, chicken ESCs were derived and established in vitro from pregastrulating embryos leading to cells with unique properties at molecular, epigenetic and developmental levels. By comparing the properties of murine, mammalian and avian ESCs and of the more recently discovered induced pluripotential stem (iPS)-derived cells generated in all of these species, avian specificities start to emerge including specific molecular genes, epigenetic mark profiles and original developmental properties. Here, we present common, but also avian-specific elements that contribute to defining avian pluripotency.

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Ten years of induced pluripotency: from basic mechanisms to therapeutic applications

Cited by 17 publications

References 23 publications

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

Pluripotency in avian species

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