Clinical potentials of human pluripotent stem cells

Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell’Era, Patrizia

doi:10.1007/s10565-017-9384-y

Cited by 67 publications

(33 citation statements)

References 80 publications

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“…Mesenchymal stem cells (MSCs) are classically defined as multipotent cells, which can differentiate into diverse cell types, including bone, cartilage, fat, tendon, muscle, and marrow stroma [54], and can be obtained from many sources, such as bone, tendon, skin, adipose tissue, umbilical cord, blood, and amnion [55]. In addition, MSCs are poorly immunogenic [56]. MSCs should be plastic adherent, have fibroblast-like morphology, express stromal markers CD73, CD90, and CD105, and be negative for the hematopoietic markers CD14, CD34, and CD45 [57].…”

Section: Neuronal Differentiation Of Mscsmentioning

confidence: 99%

Modulatory Effects of Natural Products on Neuronal Differentiation

An¹,

Chen²,

Wang³

et al. 2018

Neuropsychiatry

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Neuron loss is the cardinal characteristic of neurodegenerative diseases. Regulation of adult neurogenesis, especially the induction of neuronal differentiation, is important in developing therapies to promote neuronal regeneration from nerve injury or neurological disorders. Neuronal differentiation is extremely complicated because it can occur in different cell types and be caused by a variety of inducers. In recent years, medicinal plant-derived natural compounds have received extensive attention as major sources of new therapeutic agents for treating neurological disorders and they exert their effects by promoting adult neurogenesis. In this study, we summarized the detailed research progress on the active natural compounds with potential neuroprotective effects and their molecular mechanisms on inducing neuronal differentiation and morphogenesis in NS/PCs, MSCs, PC12 cells and neuroblastoma cells. The active ingredients derived from natural plants that efficacious in promoting neuronal differentiation and neurite outgrowth include phenolics, flavonoids, alkaloids, coumarins, terpenes, quinines, glycosides, iridoids, volatile oils and others (xanthone, isothiocyanate). Studies have shown that above natural products exert the promotion effects via regulating many factors involve in the process of neurogenesis, including specific proteins (DCX, β IIItubulin, MAP

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Section: Neuronal Differentiation Of Mscsmentioning

confidence: 99%

Modulatory Effects of Natural Products on Neuronal Differentiation

An¹,

Chen²,

Wang³

et al. 2018

Neuropsychiatry

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“…Embryonic stem cells (ESCs) are pluripotent cells capable of unlimited self-renewal and differentiation into all three germ layers [1,2], making them an attractive source for the development of in vitro disease models and drug discovery as well as tissue engineering and cellular therapies [3][4][5]. These applications require stringent conditions for characterization and expansion as well as differentiation of cells into homogenous populations of progenitors or derivatives.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

McKee

Brown

Bakshi

et al. 2020

Preprint

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Derivation of primed and naïve human embryonic stem cells (ESCs) have prompted an increased interest in devising culture conditions for maintaining their pluripotency and differential potential. Naïve ESCs are characterized by improved viability, proliferation, and differentiation capacity in comparison to primed ESCs. However, traditional two-dimensional (2-D) cell culture techniques fail to mimic the three-dimensional (3-D) in vivo microenvironment, which results in altered morphological and molecular characteristics of ESCs. Here, we describe the use of 3-D self-assembling scaffolds that support growth and maintenance of the naïve state characteristics of human ESC line, Elf1. Scaffolds were formed via a Michael addition reaction upon combination of two 8-arm polyethylene glycol (PEG) polymers functionalized with thiol (PEG-8-SH) and acrylate (PEG-8-Acr) end groups. 3-D scaffolds not only maintained the naïve state, but also supported long-term growth for up to 3 weeks without requiring routine passaging and manipulation. 3-D grown cells exhibited upregulation of core (OCT4, NANOG, and SOX2) and naïve (KLF17, KLF4, TFCP2L1, DPPA3, and DNMT3L) genes. These genes returned to normal levels when 3-D grown cells were propagated under 2-D culture conditions. Examination of RNA-sequencing demonstrated significant changes in gene expression profiles between 2-D and 3-D grown Elf1 cells. Gene Ontology analysis revealed upregulation of biological processes involved in the regulation of transcription and translation, as well as β-catenin-TCF complex assembly, extracellular matrix organization, and chromatin remodeling in 3-D grown Elf1 cells. 3-D culture conditions also induced upregulation of genes associated with several signaling pathways including Wnt signaling and focal adhesion. However, p53 signaling pathway associated genes were downregulated under these culture conditions. Our findings provide insight into the possible mechanisms of prolonged self-renewal as well as upregulation of pluripotent genes stimulated by the transduction of mechanical signals from the 3-D microenvironment.

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“…This hiPSC-based, patient-centric approach opens up great possibilities for drug development, both in terms of the scope of illnesses approachable, including disorders caused by rare mutations, as well as improved safety by the early identification of drug side effects in human cells. Nevertheless, hiPSCs are also associated with a variety of scientific challenges that must be resolved to realize the full potential of the technology (see e.g., [4,6,7,8,9,10]).…”

Section: Introductionmentioning

confidence: 99%

Improved computational identification of drug response using optical measurements of human stem cell derived cardiomyocytes in microphysiological systems

Jæger

Charwat

Charrez

et al. 2019

Preprint

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Cardiomyocytes derived from human induced pluripotent stem cells hold great potential for drug screening applications. However, their usefulness is limited by the relative immaturity of cells' electrophysiological properties as compared to native cardiomyocytes in the adult human heart. In this work, we extend and improve on methodology to address this limitation, building on previously introduced computational procedures which predict drug effects for mature cells based on changes in optical measurements of action potentials and Ca 2+ transients made in stem cell derived cardiac microtissues. This methodology quantifies ion channel changes through the inversion of data into a mathematical model, and maps this response to a mature phenotype through the assumption of functional invariance of fundamental intracellular and membrane channels during maturation.Here we utilize an updated action potential model to represent both immature and mature cells, apply an IC50-based model of dosedependent drug effects, and introduce a continuation-based optimization algorithm for analysis of dose escalation measurements using five 1 drugs with known effects. The improved methodology can identify drug induced changes more efficiently, and quantitate important metrics such as IC50 in line with published values. Consequently, the updated methodology is a step towards employing computational procedures to elucidate drug effects in mature cardiomyocytes for new drugs using stem cell-derived experimental tissues. Flux Description J sl s Flux through the RyRs from the jSR to the SL J n c Flux through the SERCA pumps from the bulk cytosol to the nSR J c d Passive diffusion flux between the dyad and the bulk cytosol J c sl Passive diffusion flux between the SL and the bulk cytosol J s n Passive diffusion flux between the nSR and the jSR J b d Free Ca 2+ binding to a buffer in the dyad J b sl Free Ca 2+ binding to a buffer in the SL J b c Free Ca 2+ binding to a buffer in the bulk cytosol J b s Free Ca 2+ binding to a buffer in the jSR J CaL Ca 2+ -flux through the L-type Ca 2+ channels from the extracellular space to the dyad J bCa Background Ca 2+ flux from the extracellular space to the SL J pCa Ca 2+ flux through the Ca 2+ pump between the extracellular space and the SL J NaCa Ca 2+ flux through the Na + -Ca 2+ exchanger between the extracellular space and the SL J sl e Total Ca 2+ flux from the extracellular space to the SL, defined as J sl e = J bCa + J pCa + J NaCa .

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Clinical potentials of human pluripotent stem cells

Cited by 67 publications

References 80 publications

Modulatory Effects of Natural Products on Neuronal Differentiation

Modulatory Effects of Natural Products on Neuronal Differentiation

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

Improved computational identification of drug response using optical measurements of human stem cell derived cardiomyocytes in microphysiological systems

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