Induced Pluripotent Stem Cells and Their Use in Cardiac and Neural Regenerative Medicine

Skalová, Štěpánka; Švadláková, Tereza; Qureshi, Wasay Mohiuddin Shaikh; Dev, Kapil; Mokrý, Jaroslav

doi:10.3390/ijms16024043

Cited by 18 publications

(8 citation statements)

References 149 publications

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“…Remarkable similarity of iPSCs to ESC, along with their origin from adult somatic cells, make iPSCs a tremendously valuable tool for regenerative medicine, disease modelling, drug discovery and testing, while avoiding the ethical concerns associated with ESC.…”

Section: Introductionmentioning

confidence: 99%

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

Sacco

Belviso

Romano

et al. 2019

J Cellular Molecular Medi

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Induced pluripotent stem cells (iPSCs) are adult somatic cells genetically reprogrammed to an embryonic stem cell‐like state. Notwithstanding their autologous origin and their potential to differentiate towards cells of all three germ layers, iPSC reprogramming is still affected by low efficiency. As dermal fibroblast is the most used human cell for reprogramming, we hypothesize that the variability in reprogramming is, at least partially, because of the skin fibroblasts used. Human dermal fibroblasts harvested from five different anatomical sites (neck, breast, arm, abdomen and thigh) were cultured and their morphology, proliferation, apoptotic rate, ability to migrate, expression of mesenchymal or epithelial markers, differentiation potential and production of growth factors were evaluated in vitro. Additionally, gene expression analysis was performed by real‐time PCR including genes typically expressed by mesenchymal cells. Finally, fibroblasts isolated from different anatomic sites were reprogrammed to iPSCs by integration‐free method. Intriguingly, while the morphology of fibroblasts derived from different anatomic sites differed only slightly, other features, known to affect cell reprogramming, varied greatly and in accordance with anatomic site of origin. Accordingly, difference also emerged in fibroblasts readiness to respond to reprogramming and ability to form colonies. Therefore, as fibroblasts derived from different anatomic sites preserve positional memory, it is of great importance to accurately evaluate and select dermal fibroblast population prior to induce reprogramming.

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Section: Introductionmentioning

confidence: 99%

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

Sacco

Belviso

Romano

et al. 2019

J Cellular Molecular Medi

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“…murine or human; embryonic or induced pluripotent) can be rather daunting and results obtained in animal cell lines may not be translatable to human cell lines. For example, the cardiomyogenic effect of ascorbic acid was first discovered in stably transfected EGFP-mouse embryonic stem cells back in 2003 [5], but in mouse induced pluripotent stem cells the yield of cardiomyocytes using ascorbic acid has recently been reported to be inconsistent [24]. Therefore, pre-existing data may indicate that ascorbic acid ought to promote cardiomyogenesis in mouse induced pluripotent stem cells, but that statement remains purely speculative, as the results apparently do not support this hypothesis.…”

Section: Bottleneck 1: Compound Screening Available Testbeds and Drumentioning

confidence: 99%

Small molecules and human cardiomyogenesis: Is there a bottleneck in current research?

Trifonov¹

2015

Biodiscovery

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“…Although fascinating, iPSCs technology is still challenging, one of the most crucial issue being the need to establish a reliable disease phenotype that can be reproduced in quite large quantities in vitro . However, once established, it could provide an invaluable resource for drug target identification and drug screening ( Skalova et al, 2015 ; Watson et al, 2015 ).…”

Section: Future Perspective In Drug Discoverymentioning

confidence: 99%

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

et al. 2016

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In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.

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Induced Pluripotent Stem Cells and Their Use in Cardiac and Neural Regenerative Medicine

Cited by 18 publications

References 149 publications

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

Small molecules and human cardiomyogenesis: Is there a bottleneck in current research?

Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

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