scholarly journals Bioink Composition and Printing Parameters for 3D Modeling Neural Tissue

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 830 ◽  
Author(s):  
Valentina Fantini ◽  
Matteo Bordoni ◽  
Franca Scocozza ◽  
Michele Conti ◽  
Eveljn Scarian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Broad Class ◽  
Neuroblastoma Cell ◽  
Neural Tissue ◽  
Cell Types ◽  
Neuroblastoma Cell Line ◽  
3D Bioprinting ◽  
Vitro Model ◽  
Induced Pluripotent

Neurodegenerative diseases (NDs) are a broad class of pathologies characterized by the progressive loss of neurons in the central nervous system. The main problem in the study of NDs is the lack of an adequate realistic experimental model to study the pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) partially overcome the problem, with their capability to differentiate into almost every cell types; even so, these cells alone are not sufficient to unveil the mechanisms underlying NDs. 3D bioprinting allows to control the distribution of cells such as neurons, leading to the creation of a realistic in vitro model. In this work, we analyzed two biomaterials: sodium alginate and gelatin, and three different cell types: a neuroblastoma cell line (SH-SY5Y), iPSCs, and neural stem cells. All cells were encapsulated inside the bioink, printed and cultivated for at least seven days; they all presented good viability. We also evaluated the maintenance of the printed shape, opening the possibility to obtain a reliable in vitro neural tissue combining 3D bioprinting and iPSCs technology, optimizing the study of the degenerative processes that are still widely unknown.

scholarly journals Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Glial Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

scholarly journals Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

2021 ◽  
Author(s):  
Aida Nourbakhsh ◽  
Brett M. Colbert ◽  
Eric Nisenbaum ◽  
Aziz El-Amraoui ◽  
Derek M. Dykxhoorn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Hearing Loss ◽  
Treatment Modalities ◽  
Versus Gene ◽  
Vitro Model ◽  
New Treatment ◽  
Induced Pluripotent ◽  
Therapy Strategies

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

scholarly journals Use of organoids to study regenerative responses to intestinal damage

2019 ◽  
Vol 317 (6) ◽  
pp. G845-G852 ◽  
Author(s):  
Sarah E. Blutt ◽  
Ophir D. Klein ◽  
Mark Donowitz ◽  
Noah Shroyer ◽  
Chandan Guha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Parasitic Infection ◽  
Genetically Modify ◽  
Intestinal Wall ◽  
Intestinal Damage ◽  
Therapeutic Modalities ◽  
Epithelial Regeneration ◽  
Vitro Model ◽  
Induced Pluripotent

Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derived from either embryonic or induced pluripotent stem cells or adult intestinal stem cells or tissues, these self-organizing, multicellular structures contain polarized mature cells that recapitulate both the physiology and heterogeneity of the intestinal epithelium. These cultures provide a cutting-edge technology for defining regenerative pathways that are induced following radiation or chemical damage, which directly target the cycling intestinal stem cell, or damage resulting from viral, bacterial, or parasitic infection of the epithelium. Novel signaling pathways or biological mechanisms identified from organoid studies that mediate regeneration of the epithelium following damage are likely to be important targets of preventive or therapeutic modalities to mitigate intestinal injury. The evolution of these cultures to include more components of the intestinal wall and the ability to genetically modify them are key components for defining the mechanisms that modulate epithelial regeneration.

scholarly journals Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1306
Author(s):  
Ann-Kristin Afflerbach ◽  
Mark D. Kiri ◽  
Tahir Detinis ◽  
Ben M. Maoz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
In Vitro Models ◽  
Cell Source ◽  
Fundamental Research ◽  
Multiple Cell ◽  
Vitro Model

The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research.

scholarly journals Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pauline Georges ◽  
Maria-Gabriela Boza-Moran ◽  
Jacqueline Gide ◽  
Georges Arielle Pêche ◽  
Benjamin Forêt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Friedreich Ataxia ◽  
Cell Types ◽  
Differential Sensitivity ◽  
Human Ipscs ◽  
Induced Pluripotent ◽  
Species Specific

Abstract Translation of pharmacological results from in vitro cell testing to clinical trials is challenging. One of the causes that may underlie these discrepant results is the lack of the phenotypic or species-specific relevance of the tested cells; today, this lack of relevance may be reduced by relying on cells differentiated from human pluripotent stem cells. To analyse the benefits provided by this approach, we chose to focus on Friedreich ataxia, a neurodegenerative condition for which the recent clinical testing of two compounds was not successful. These compounds, namely, resveratrol and nicotinamide, were selected because they had been shown to stimulate the expression of frataxin in fibroblasts and lymphoblastoid cells. Our results indicated that these compounds failed to do so in iPSC-derived neurons generated from two patients with Friedreich ataxia. By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.

scholarly journals Chromosomal Abnormalities in Embryonic and Somatic Stem Cells

2015 ◽  
Vol 147 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Paola Rebuzzini ◽  
Maurizio Zuccotti ◽  
Carlo A. Redi ◽  
Silvia Garagna
Keyword(s):  
Stem Cells ◽  
Large Scale ◽  
In Vitro Model ◽  
Disease Modeling ◽  
Chromosomal Abnormalities ◽  
Toxicological Studies ◽  
Vitro Model ◽  
Induced Pluripotent ◽  
Potential Use

The potential use of stem cells (SCs) for tissue engineering, regenerative medicine, disease modeling, toxicological studies, drug delivery, and as in vitro model for the study of basic developmental processes implies large-scale in vitro culture. Here, after a brief description of the main techniques used for karyotype analysis, we will give a detailed overview of the chromosome abnormalities described in pluripotent (embryonic and induced pluripotent SCs) and somatic SCs, and the possible causes of their origin during culture.

Cardiomyocyte culture — an update on the in vitro cardiovascular model and future challenges

2013 ◽  
Vol 91 (12) ◽  
pp. 985-998 ◽  
Author(s):  
Sreejit Parameswaran ◽  
Sujeet Kumar ◽  
Rama Shanker Verma ◽  
Rajendra K. Sharma
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Small Animal ◽  
Heart Tissue ◽  
Cellular Level ◽  
Future Challenges ◽  
Vitro Model ◽  
Induced Pluripotent

The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac surgical waste or, alternatively, from fetal heart tissue is another option. However, to overcome various issues related to human tissue usage, especially ethical concerns, researchers use large- and small-animal models to study cardiac pathophysiology. A simple model to study the changes at the cellular level is cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have their own advantages and drawbacks, alternative strategies have been developed in the last two decades to minimise animal usage and interspecies differences. This review discusses the use of freshly isolated murine cardiomyocytes and cardiomyocyte alternatives for use in cardiac disease models and other related studies.

scholarly journals Development of a Personalized Intestinal Fibrosis Model Using Human Intestinal Organoids Derived From Induced Pluripotent Stem Cells

2021 ◽  
Author(s):  
Hannah Q Estrada ◽  
Shachi Patel ◽  
Shervin Rabizadeh ◽  
David Casero ◽  
Stephan R Targan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Rna Sequencing ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Mesenchymal Cells ◽  
Sequencing Analysis ◽  
Intestinal Fibrosis ◽  
Induced Pluripotent

Abstract Background Intestinal fibrosis is a serious complication of Crohn’s disease. Numerous cell types including intestinal epithelial and mesenchymal cells are implicated in this process, yet studies are hampered by the lack of personalized in vitro models. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain these cell types, and our goal was to determine the feasibility of utilizing these to develop a personalized intestinal fibrosis model. Methods iPSCs from 2 control individuals and 2 very early onset inflammatory bowel disease patients with stricturing complications were obtained and directed to form HIOs. Purified populations of epithelial and mesenchymal cells were derived from HIOs, and both types were treated with the profibrogenic cytokine transforming growth factor β (TGFβ). Quantitative polymerase chain reaction and RNA sequencing analysis were used to assay their responses. Results In iPSC-derived mesenchymal cells, there was a significant increase in the expression of profibrotic genes (Col1a1, Col5a1, and TIMP1) in response to TGFβ. RNA sequencing analysis identified further profibrotic genes and demonstrated differential responses to this cytokine in each of the 4 lines. Increases in profibrotic gene expression (Col1a1, FN, TIMP1) along with genes associated with epithelial-mesenchymal transition (vimentin and N-cadherin) were observed in TGFβ -treated epithelial cells. Conclusions We demonstrate the feasibility of utilizing iPSC-HIO technology to model intestinal fibrotic responses in vitro. This now permits the generation of near unlimited quantities of patient-specific cells that could be used to reveal cell- and environmental-specific mechanisms underpinning intestinal fibrosis.

scholarly journals Generation of Sheep Induced Pluripotent Stem Cells With Defined DOX-Inducible Transcription Factors via piggyBac Transposition

2021 ◽  
Vol 9 ◽  
Author(s):  
Moning Liu ◽  
Lixia Zhao ◽  
Zixin Wang ◽  
Hong Su ◽  
Tong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
T Antigen ◽  
Sv40 Large T Antigen ◽  
Adult Individual ◽  
Induced Pluripotent

Pluripotent stem cells (PSCs) have the potential to differentiate to all cell types of an adult individual and are useful for studying mammalian development. Establishing induced pluripotent stem cells (iPSCs) capable of expressing pluripotent genes and differentiating to three germ layers will not only help to explain the mechanisms underlying somatic reprogramming but also lay the foundation for the establishment of sheep embryonic stem cells (ESCs) in vitro. In this study, sheep somatic cells were reprogrammed in vitro into sheep iPSCs with stable morphology, pluripotent marker expression, and differentiation ability, delivered by piggyBac transposon system with eight doxycycline (DOX)-inducible exogenous reprogramming factors: bovine OCT4, SOX2, KLF4, cMYC, porcine NANOG, human LIN28, SV40 large T antigen, and human TERT. Sheep iPSCs exhibited a chimeric contribution to the early blastocysts of sheep and mice and E6.5 mouse embryos in vitro. A transcriptome analysis revealed the pluripotent characteristics of somatic reprogramming and insights into sheep iPSCs. This study provides an ideal experimental material for further study of the construction of totipotent ESCs in sheep.

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