scholarly journals Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sally K. Mak ◽  
Y. Anne Huang ◽  
Shifteh Iranmanesh ◽  
Malini Vangipuram ◽  
Ramya Sundararajan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Neuronal Differentiation ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Specific Cell ◽  
Neuronal Marker ◽  
Neural Lineage ◽  
Induced Pluripotent

Efficientin vitrodifferentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson’s disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.

scholarly journals Derivation of induced pluripotent stem cells from ferret somatic cells

2020 ◽  
Vol 318 (4) ◽  
pp. L671-L683
Author(s):  
Jinghui Gao ◽  
Sophia Petraki ◽  
Xingshen Sun ◽  
Leonard A. Brooks ◽  
Thomas J. Lynch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Preclinical Model ◽  
Specific Cell ◽  
Chronic Lung Diseases ◽  
Human Ipscs ◽  
Fetal Fibroblasts ◽  
Induced Pluripotent

Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung, where ferrets provide an attractive mammalian model of both acute and chronic lung diseases, such as influenza, cystic fibrosis, A1A emphysema, and obliterative bronchiolitis, closely recapitulating disease pathogenesis, as it occurs in humans. As such, ferrets have the potential to be a valuable preclinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multilineage differentiation, and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.

scholarly journals The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Joseph M. Schulz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Cells ◽  
Patient Specific ◽  
Specific Cell ◽  
Induced Pluripotent

An estimated 6.2 million Americans aged 65 or older are currently living with Alzheimer’s disease (AD), a neurodegenerative disease that disrupts an individual’s ability to function independently through the degeneration of key regions in the brain, including but not limited to the hippocampus, the prefrontal cortex, and the motor cortex. The cause of this degeneration is not known, but research has found two proteins that undergo posttranslational modifications: tau, a protein concentrated in the axons of neurons, and amyloid precursor protein (APP), a protein concentrated near the synapse. Through mechanisms that have yet to be elucidated, the accumulation of these two proteins in their abnormal aggregate forms leads to the neurodegeneration that is characteristic of AD. Until the invention of induced pluripotent stem cells (iPSCs) in 2006, the bulk of research was carried out using transgenic animal models that offered little promise in their ability to translate well from benchtop to bedside, creating a bottleneck in the development of therapeutics. However, with iPSC, patient-specific cell cultures can be utilized to create models based on human cells. These human cells have the potential to avoid issues in translatability that have plagued animal models by providing researchers with a model that closely resembles and mimics the neurons found in humans. By using human iPSC technology, researchers can create more accurate models of AD ex vivo while also focusing on regenerative medicine using iPSC in vivo. The following review focuses on the current uses of iPSC and how they have the potential to regenerate damaged neuronal tissue, in the hopes that these technologies can assist in getting through the bottleneck of AD therapeutic research.

scholarly journals Reprogramming with Small Molecules instead of Exogenous Transcription Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Tongxiang Lin ◽  
Shouhai Wu
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mouse Embryonic Fibroblast ◽  
Patient Specific ◽  
Full Potential ◽  
Ipsc Generation ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical applications. However, current iPSC methodologies present significant hidden risks with respect to genetic mutations and abnormal expression which are a barrier in realizing the full potential of iPSCs. A chemical approach is thought to be a promising strategy for safety and efficiency of iPSC generation. Many small molecules have been identified that can be used in place of exogenous transcription factors and significantly improve iPSC reprogramming efficiency and quality. Recent studies have shown that the use of small molecules results in the generation of chemically induced pluripotent stem cells from mouse embryonic fibroblast cells. These studies might lead to new areas of stem cell research and medical applications, not only human iPSC by chemicals alone, but also safe generation of somatic stem cells for cell based clinical trials and other researches. In this paper, we have reviewed the recent advances in small molecule approaches for the generation of iPSCs.

scholarly journals Selected small molecules as inductors of pluripotent stem cells

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Małgorzata Baranek ◽  
Wojciech T Markiewicz ◽  
Jan Barciszewski
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
General Idea ◽  
Patient Specific ◽  
General Character ◽  
Induced Pluripotent

The general idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are capable of indefinite self-renewal and differentiation into all cell types of body with origin from the three germ layers of the developing embryo, therefore they have a potential to play a substantial role in regenerative medicine. Easily accessible source of induced pluripotent stem cells may allow obtaining and culturing tissues in vitro. Many improvements in the methods leading to obtain such cells have been made by various research groups in order to limit immunogenicity and tumorigenesis, increase efficiency and accelerate kinetics. One of the approaches affecting pluripotency is usage of small molecule compounds including RNA-derivatives – nucleosides analogues. It would be great to assess general character of such molecules and reveal their new derivatives or modifications to improve induced pluripotent stem cells (iPSCs) reprogramming efficiency. Understanding the epigenetic changes during cellular reprogramming will extend understanding of stem cell biology and lead to potential therapeutic approaches. In this digest of compounds found in literature as proven or putative inductors of cells’ reprogramming to pluripotency there are compounds that may substitute for transgenic nucleic acids delivery in order to improve time and efficiency of reprogramming. Nucleic acids’ derivatives or modifications of particular atoms or substitutes influence modulating activities of small molecules, especially their inhibiting activity.  Due to dosage-dependent effect of small molecules influence on genes, their application concentration needs to be strictly determined.

scholarly journals Increased Neuronal Differentiation Efficiency in High Cell Density-Derived Induced Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Sumitra Srimasorn ◽  
Matthias Kirsch ◽  
Susanne Hallmeyer-Ellgner ◽  
Dirk Lindemann ◽  
Alexander Storch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Neuronal Differentiation ◽  
Cell Density ◽  
Pluripotent Stem Cells ◽  
Seeding Density ◽  
Differentiation Potential ◽  
Neural Lineage ◽  
Induced Pluripotent

Human pluripotent stem cells (hPSCs), including induced pluripotent stem cells (iPSCs), provide access to hard-to-obtain cells for studies under physiological and disease conditions. For the study of neurodegenerative diseases, especially sporadic cases where the “disease condition” might be restricted towards the neuroectodermal lineage, obtaining the affected neurons is important to help unravel the underlying molecular mechanism leading to the diseases. Although differentiation of iPSCs to neural lineage allows acquisition of cell types of interest, the technology suffers from low efficiency leading to low yield of neurons. Here, we investigated the potential of adult neuroprogenitor cells (aNPCs) for iPSC derivation and possible confounders such as cell density of infected NPCs on their subsequent neuronal differentiation potential from reprogrammed cells under isogenic conditions. Characterized hiPSCs of defined cell densities generated from aNPCs were subjected to neuronal differentiation on PA6 stromal cells. The results showed that hiPSC clones obtained from low seeding density (iPSC-aNPCLow) differentiated less efficiently compared to those from higher density (iPSC-aNPCHigh). Our findings might help to further improve the yield and quality of neurons for in vitro modelling of neurodegenerative diseases.

scholarly journals Temporal mechanisms of myogenic specification in human induced pluripotent stem cells

2021 ◽  
Vol 7 (12) ◽  
pp. eabf7412
Author(s):  
P. Nayak ◽  
A. Colas ◽  
M. Mercola ◽  
S. Varghese ◽  
S. Subramaniam
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Cellular Processes ◽  
Transcriptional Cofactors ◽  
Extracellular Matrix Components ◽  
Cell Subpopulations ◽  
Longitudinal Comparison ◽  
Induced Pluripotent

Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differentiate into myocytes. To address the unique cellular and temporal context of hiPSC differentiation, we perform a longitudinal comparison of the transcriptomic profiles of three hiPSC lines that display differential myogenic specification, one robust and two blunted. We detail temporal differences in mechanisms that lead to robust myogenic specification. We show gene expression signatures of putative cell subpopulations and extracellular matrix components that may support myogenesis. Furthermore, we show that targeted knockdown of ZIC3 at the outset of differentiation leads to improved myogenic specification in blunted hiPSC lines. Our study suggests that β-catenin transcriptional cofactors mediate cross-talk between multiple cellular processes and exogenous cues to facilitate specification of hiPSCs to mesoderm lineage, leading to robust myogenesis.

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