scholarly journals Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

2020 ◽  
Vol 10 (1) ◽  
pp. 8 ◽  
Author(s):  
Chiara Argentati ◽  
Ilaria Tortorella ◽  
Martina Bazzucchi ◽  
Francesco Morena ◽  
Sabata Martino
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
Ex Vivo ◽  
Pharmaceutical Research ◽  
Disease Models ◽  
Cell Models ◽  
Human Stem Cells ◽  
Induced Pluripotent

Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.

scholarly journals Intestinal Organoids—Current and Future Applications

2016 ◽  
Author(s):  
Andre M. C. Meneses ◽  
Kerstin Schneeberger ◽  
Hedwig S. Kruitwagen ◽  
Louis C. Penning ◽  
Frank G. van Steenbeek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Intestinal Stem Cells ◽  
Complex Structures ◽  
Technical Advances ◽  
Induced Pluripotent

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

scholarly journals Stem Cell-Based Disease Models for Inborn Errors of Immunity

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 108
Author(s):  
Aline Zbinden ◽  
Kirsten Canté-Barrett ◽  
Karin Pike-Overzet ◽  
Frank J. T. Staal
Keyword(s):  
Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Disease Models ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Inborn Errors Of Immunity ◽  
Induced Pluripotent

The intrinsic capacity of human hematopoietic stem cells (hHSCs) to reconstitute myeloid and lymphoid lineages combined with their self-renewal capacity hold enormous promises for gene therapy as a viable treatment option for a number of immune-mediated diseases, most prominently for inborn errors of immunity (IEI). The current development of such therapies relies on disease models, both in vitro and in vivo, which allow the study of human pathophysiology in great detail. Here, we discuss the current challenges with regards to developmental origin, heterogeneity and the subsequent implications for disease modeling. We review models based on induced pluripotent stem cell technology and those relaying on use of adult hHSCs. We critically review the advantages and limitations of current models for IEI both in vitro and in vivo. We conclude that existing and future stem cell-based models are necessary tools for developing next generation therapies for IEI.

scholarly journals Rapid Differentiation From Human Induced Pluripotent Stem Cells Into Functional Oligodendrocytes Using Synthetic Modified Olig2 mRNA

2022 ◽  
Author(s):  
Jian Xu ◽  
Rui Wang ◽  
Jingxin Zhao ◽  
Fumei He ◽  
Yidi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Disease Modeling ◽  
Ex Vivo ◽  
Phosphorylation Site ◽  
Induced Pluripotent

Abstract Background: Transcription factors (TFs) have been introduced to drive highly efficient differentiation of human induced pluripotent stem cells (hiPSCs) into lineage-specific oligodendrocytes (OLs). However, effective strategies currently rely mainly on genome-integrating viruses. To facilitate the translation of hiPSC-derived OLs into clinical practice, a synthetic modified messenger RNA (smRNA) reprogramming method that generates transgene-free OLs has been developed.Methods: An smRNA encoding Olig2, a key TF in OL development, with a defined phosphorylation site modification serine 147 replaced with alanine, Olig2S147A, was designed to reprogram hiPSCs into OLs. Proteomics were used to identify Olig2S147A-binding proteins that positively mediated of Olig2S147A-driven OL differentiation.Results: We demonstrated that repeated administration of the smRNA encoding Olig2 S147A led to higher and more stable protein expression. Using the single-mutant Olig2 smRNA with morphogens, we established a 6-day smRNA transfection protocol, and glial induction led to rapid NG2+ OL progenitor cell (OPC) generation (>70% purity) from hiPSC-derived neural progenitor cells (NPCs). The smRNA-induced NG2+ OPCs matured into functional OLs and myelinated nanofibers in vitro. Moreover, when transplanted into mice with cuprizone-induced demyelination, smRNA-induced OPCs promoted remyelination ex vivo. A proteomic analysis of Olig2-binding proteins indicated that the heat shock protein 70 (HSP70) complex bound Olig2. The HSP70 complex bound more strongly to Olig2 with the modified phosphorylation site than to wild type Olig2. VER-155008, an HSP70 complex antagonist, and ML346, an HSP70 complex agonist, inhibited and promoted Olig2 transcriptional activity and efficient OL generation, respectively.Conclusions: We present a very safe and efficient smRNA-driven strategy for hiPSC differentiation into OLs, which might be utilized for disease modeling, drug discovery, and/or therapeutic OPC/OL transplantation in neurodegenerative disease.

scholarly journals Disease Modeling and Disease Gene Discovery in Cardiomyopathies: A Molecular Study of Induced Pluripotent Stem Cell Generated Cardiomyocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3311
Author(s):  
Satish Kumar ◽  
Joanne E. Curran ◽  
Kashish Kumar ◽  
Erica DeLeon ◽  
Ana C. Leandro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Disease Gene ◽  
Disease Modeling ◽  
Gene Discovery ◽  
Induced Pluripotent Stem Cell ◽  
P Value ◽  
Disease Gene Discovery ◽  
Induced Pluripotent

The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The generated CMs expressed CM-specific genes and were highly concordant in their total expressed transcriptome across the 12 samples (correlation coefficient at 95% CI =0.92 ± 0.02). The functional annotation and enrichment analysis of the 2116 genes that were significantly upregulated in CMs suggest that generated CMs have a transcriptomic and functional profile of immature atrial-like CMs; however, the CMs-upregulated transcriptome also showed high overlap and significant enrichment in primary cardiomyocyte (p-value = 4.36 × 10−9), primary heart tissue (p-value = 1.37 × 10−41) and cardiomyopathy (p-value = 1.13 × 10−21) associated gene sets. Modeling the effect of MACE in the generated CMs-upregulated transcriptome identified gene expression phenotypes consistent with the predisposition of the MACE-affected sibship to arrhythmia, prothrombotic, and atherosclerosis risk.

scholarly journals The Promise of Human Induced Pluripotent Stem Cells in Dental Research

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Dental Research ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Disease Specific

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

Stem cells in brain diseases: From cell replacement to disease modeling

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Nina Kosi ◽  
Dinko Mitrečić
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
Neurological Diseases ◽  
Rapid Development ◽  
Modern Society ◽  
Brain Diseases ◽  
Stem Cell Technology ◽  
Cell Based Therapy

AbstractNeurological diseases are recognized as one of the most significant burdens of the modern society. Therefore, a new therapeutic approach applicable to nervous system represents priority of today’s medicine. A rapid development of stem cell technology in the last two decades introduced a possibility to regenerate disease-affected nervous tissue. In this vein, stem cells are envisioned as a replacement for lost neurons, a source of trophic support, a therapeutic vehicle, and as a tool for in vitro modeling. This article reviews the current concepts in stem cell-based therapy of neurological diseases and comments ongoing efforts aiming at clinical translation.

scholarly journals Generation of star-shaped human induced astrocytes with a mature inflammatory phenotype for CNS disease modeling

2021 ◽  
Author(s):  
Dimitrios Voulgaris ◽  
Polyxeni Nikolakopoulou ◽  
Anna Herland
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Glutamate Transporter ◽  
Cns Disease ◽  
Human Neural Stem Cells ◽  
Induced Pluripotent ◽  
Prolonged Differentiation

Generating astrocytes from induced pluripotent stem cells has been hampered by either prolonged differentiation -spanning over two months -or by shorter protocols that generate immature astrocytes, devoid of salient inflammation-associated astrocytic traits pivotal for CNS neuropathological modeling. We directed human neural stem cells derived from induced pluripotent stem cells to astrocytic commitment and maturity by orchestrating an astrocytic-tuned culturing environment. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of AQP4 and, remarkably, the expression and functionality of glutamate transporter EAAT2. We also show that this protocol generates astrocytes that encompass traits critical in CNS disease modeling, such as glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile which is on par with primary astrocytes. This protocol generates a multifaceted astrocytic model suitable for CNS in vitro disease modeling and personalized medicine through brain-on-chip technologies.

Application of biomaterials to in vitro pluripotent stem cell disease modeling of the skeletal system

2016 ◽  
Vol 4 (20) ◽  
pp. 3482-3489 ◽  
Author(s):  
Giuliana E. Salazar-Noratto ◽  
Frank P. Barry ◽  
Robert E. Guldberg
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Genetic Manipulation ◽  
Embryonic Stem ◽  
Cell Disease ◽  
Skeletal System ◽  
System P ◽  
Induced Pluripotent

Disease-specific pluripotent stem cells can be derived through genetic manipulation of embryonic stem cells or by reprogramming somatic cells (induced pluripotent stem cells).

scholarly journals Dose-Independent Therapeutic Benefit of Bone Marrow Stem Cell Transplantation after MI in Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 157
Author(s):  
Nicole Zarniko ◽  
Anna Skorska ◽  
Gustav Steinhoff ◽  
Robert David ◽  
Ralf Gaebel
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Ex Vivo ◽  
Therapeutic Benefit ◽  
Dependent Manner ◽  
Mesenchymal Progenitors

Several cell populations derived from bone marrow (BM) have been shown to possess cardiac regenerative potential. Among these are freshly isolated CD133+ hematopoietic as well as culture-expanded mesenchymal stem cells. Alternatively, by purifying CD271+ cells from BM, mesenchymal progenitors can be enriched without an ex vivo cultivation. With regard to the limited available number of freshly isolated BM-derived stem cells, the effect of the dosage on the therapeutic efficiency is of particular interest. Therefore, in the present pre-clinical study, we investigated human BM-derived CD133+ and CD271+ stem cells for their cardiac regenerative potential three weeks post-myocardial infarction (MI) in a dose-dependent manner. The improvement of the hemodynamic function as well as cardiac remodeling showed no therapeutic difference after the transplantation of both 100,000 and 500,000 stem cells. Therefore, beneficial stem cell transplantation post-MI is widely independent of the cell dose and detrimental stem cell amplification in vitro can likely be avoided.

Long-Term Ex Vivo Maintenance and Expansion of Transplantable Human Hematopoietic Stem Cells

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1623-1636 ◽  
Author(s):  
Chu-Chih Shih ◽  
Mickey C.-T. Hu ◽  
Jun Hu ◽  
Jeffrey Medeiros ◽  
Stephen J. Forman
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
In Vitro Culture ◽  
Culture System ◽  
Ex Vivo ◽  
Human Stem Cells ◽  
Hematopoietic Stem ◽  
In Vitro Culture System

Abstract We have developed a stromal-based in vitro culture system that facilitates ex vivo expansion of transplantable CD34+thy-1+ cells using long-term hematopoietic reconstitution in severe combined immunodeficient-human (SCID-hu) mice as an in vivo assay for transplantable human hematopoietic stem cells (HSCs). The addition of leukemia inhibitory factor (LIF) to purified CD34+ thy-1+ cells on AC6.21 stroma, a murine bone marrow–derived stromal cell line, caused expansion of cells with CD34+ thy-1+ phenotype. Addition of other cytokines, including interleukin-3 (IL-3), IL-6, granulocyte-macrophage colony-stimulating factor, and stem cell factor, to LIF in the cultures caused a 150-fold expansion of cells retaining the CD34+ thy-1+ phenotype. The ex vivo–expanded CD34+ thy-1+ cells gave rise to multilineage differentiation, including myeloid, T, and B cells, when transplanted into SCID-hu mice. Both murine LIF (cannot bind to human LIF receptor) and human LIF caused expansion of human CD34+ thy-1+ cells in vitro, suggesting action through the murine stroma. Furthermore, another human HSC candidate, CD34+ CD38− cells, shows a similar pattern of proliferative response. This suggests thatex vivo expansion of transplantable human stem cells under this in vitro culture system is a general phenomenon and not just specific for CD34+ thy-1+ cells.

Sign in / Sign up

Export Citation Format

Share Document