Induced Pluripotent Stem Cells as a Disease Modeling and Drug Screening Platform

Ebert, Antje; Liang, Ping; Wu, Joseph C.

doi:10.1097/fjc.0b013e318247f642

Cited by 176 publications

(121 citation statements)

References 127 publications

(141 reference statements)

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“…iPSC are used for in vitro development and testing of new therapeutic agents and regimens [457], for high-throughput drug screening [458,459] and imaging in industrial platforms [460]. iPSC have been derived from HGPS [461] and Werner syndrome cells [462].…”

Section: Induced Pluripotent Stem Cells (Ipsc)mentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

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Section: Induced Pluripotent Stem Cells (Ipsc)mentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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“…The concept of in vitro replication of human disease phenotypes in specialized cells derived from patientspecific iPS cells already has gained at least partial validation for a number of neurologic, hematopoietic, cardiovascular, and metabolic disorders (Unternaehrer and Daley, 2011;Ebert et al, 2012;Maury et al, 2012;Rajamohan et al, 2013). Examples of specific conditions for which patient-specific iPS cells have been obtained and differentiated into disease-relevant cell types include Parkinson's disease (Byers et al, 2012;Jang et al, 2012) and other neurodegenerative disorders Jung et al, 2012), Wilson's disease (Yi et al, 2012), lysosomal storage disorders (Huang et al, 2012b), and diabetes (Fujikura et al, 2012).…”

Section: Disease Models From Patient-specific Reprogrammed Cellsmentioning

confidence: 99%

The Pharmacology of Regenerative Medicine

et al. 2013

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“…Since these cells have a similar potential as human embryonic stem cells with less ethical concerns (Murphy et al 2013), they can virtually be differentiated into each specialized cell of the human body (Lee et al 2010;Lancaster and Knoblich 2014;Kempf et al 2015). Furthermore, hiPSCs can be generated from patients with genetic disorders, and thus, the corresponding cells can be used for patient-specific drug testing (Gunaseeli et al 2010;Ebert et al 2012). In this context, compliant bioactive hydrogels can enhance both the current workflows during differentiation and the subsequent generated cell models.…”

Section: Introductionmentioning

confidence: 99%

Bioactive surfaces from seaweed-derived alginates for the cultivation of human stem cells

et al. 2017

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Nowadays, modern approaches in tissue engineering include the combination of therapeutic relevant cells with high quality, biocompatible biomaterials. The resulting cellularized scaffolds are of great interest for several pharmaceutical applications such as drug screening/discovery, disease modeling, and toxicity testing. In addition, the introduction of human-induced pluripotent stem cells (hiPSCs) further increased the importance and the potential of tissue engineering not only for the pharmaceutical industry, but also for future therapeutic applications. Artificial microenvironments of hiPSCs comprise combinations of adhesive proteins and are particularly influenced by mechanical properties of the growth surface. The increasing focus on mechanical properties and the ability to adjust them propose alginate hydrogels as suitable candidates for engineered scaffolds. Ultra-pure alginates, however, are bioinert and require modifications for bioactivation. In this study, we present two modifications of alginate hydrogels based on direct covalent coupling of collagen I and coupling of a special linker molecule with subsequent Matrigel coating. We were able to demonstrate the successful adhesion and proliferation of hiPSCs on these linkermodified alginates. The developed modifications are particularly applicable for planar as well as spherical hydrogel surfaces. In this context, a scalable adherent suspension culture on alginate microcarriers could be established. Our data further indicate that larger alginate microcarriers modified with collagen I is less susceptible for agglomeration compared to small microcarriers. The obtained results indicate these modifications as suitable for both adhesion and cultivation of human stem cells such as human mesenchymal stem cells or hiPSCs.

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Induced Pluripotent Stem Cells as a Disease Modeling and Drug Screening Platform

Cited by 176 publications

References 127 publications

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

The Pharmacology of Regenerative Medicine

Bioactive surfaces from seaweed-derived alginates for the cultivation of human stem cells

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