scholarly journals Current biomarker-associated procedures of cancer modeling-a reference in the context of IDH1 mutant glioma

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Narges Zare Mehrjardi ◽  
Daniel Hänggi ◽  
Ulf Dietrich Kahlert
Keyword(s):  
Cell Biology ◽  
Disease Modeling ◽  
Therapeutic Strategies ◽  
Stem Cell Biology ◽  
Clinical Context ◽  
In Vivo Models ◽  
The Core ◽  
Research Questions

AbstractIsocitrate dehydrogenases (IDH1/2) are central molecular markers for glioblastoma. Providing in vitro or in vivo models with mutated IDH1/2 can help prepare facilities to understand the biology of these mutated genes as glioma markers, as well as help, improve therapeutic strategies. In this review, we first summarize the biology principles of IDH and its mutations and outline the core primary findings in the clinical context of neuro-oncology. Given the extensive research interest and exciting developments in current stem cell biology and genome editing, the central part of the manuscript is dedicated to introducing various routes of disease modeling strategies of IDH mutation (IDHMut) glioma and comparing the scientific-technological findings from the field using different engineering methods. Lastly, by giving our perspective on the benefits and limitations of patient-derived and donor-derived disease modeling respectively, we aim to propose leading research questions to be answered in the context of IDH1 and glioma.

scholarly journals Organoids from the Human Fetal and Adult Pancreas

2019 ◽  
Vol 19 (12) ◽  
Author(s):  
Jeetindra R. A. Balak ◽  
Juri Juksar ◽  
Françoise Carlotti ◽  
Antonio Lo Nigro ◽  
Eelco J. P. de Koning
Keyword(s):  
Cell Biology ◽  
Cell Formation ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Disease Modelling ◽  
In Vivo Models ◽  
Pancreatic Cell ◽  
Culture Techniques

Abstract Purpose of Review Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue–derived pancreatic organoids in regenerative studies, disease modelling, and personalized medicine. Recent Findings Organoids derived from human fetal and adult pancreatic tissue have been used to study pancreas development and repair. Generated adult human pancreatic organoids harbor the capacity for clonal expansion and endocrine cell formation. In addition, organoids have been generated from human pancreatic ductal adenocarcinoma in order to study tumor behavior and assess drug responses. Summary Pancreatic organoids constitute an important translational bridge between in vitro and in vivo models, enhancing our understanding of pancreatic cell biology. Current applications for pancreatic organoid technology include studies on tissue regeneration, disease modelling, and drug screening.

The Role of Nucleophosmin In Hematopoietic Stem Cells and the Pathogenesis of Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 95-95 ◽  
Author(s):  
Keisuke Ito ◽  
Paolo Sportoletti ◽  
John G Clohessy ◽  
Grisendi Silvia ◽  
Pier Paolo Pandolfi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cell Biology ◽  
De Novo ◽  
Stem Cell Biology ◽  
Hematopoietic Stem

Abstract Abstract 95 Myelodysplastic syndrome (MDS) is an incurable stem cell disorder characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Nucleophosmin (NPM) is directly implicated in primitive hematopoiesis, the pathogenesis of hematopoietic malignancies and more recently of MDS. However, little is known regarding the molecular role and function of NPM in MDS pathogenesis and in stem cell biology. Here we present data demonstrating that NPM plays a critical role in the maintenance of hematopoietic stem cells (HSCs) and the transformation of MDS into leukemia. NPM is located on chromosome 5q and is frequently lost in therapy-related and de novo MDS. We have previously shown that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment and Npm1+/− mice develop a hematologic syndrome with features of human MDS, including increased susceptibility to leukemogenesis. As HSCs have been demonstrated to be the target of the primary neoplastic event in MDS, a functional analysis of the HSC compartment is essential to understand the molecular mechanisms in MDS pathogenesis. However, the role of NPM in adult hematopoiesis remains largely unknown as Npm1-deficiency leads to embryonic lethality. To investigate NPM function in adult hematopoiesis, we have generated conditional knockout mice of Npm1, using the Cre-loxP system. Analysis of Npm1 conditional mutants crossed with Mx1-Cre transgenic mice reveals that Npm1 plays a crucial role in adult hematopoiesis and ablation of Npm1 in adult HSCs leads to aberrant cycling and followed by apoptosis. Analysis of cell cycle status revealed that HSCs are impaired in their ability to maintain quiescence after Npm1-deletion and are rapidly depleted in vivo as well as in vitro. Competitive reconstitution assay revealed that Npm1 acts cell-autonomously to maintain HSCs. Conditional inactivation of Npm1 leads to an MDS phenotype including a profoundly impaired ability to differentiate into cells of the erythroid lineage, megakaryocyte dyspoiesis and centrosome amplification. Furthermore, Npm1 loss evokes a p53-dependent response and Npm1-deleted HSCs undergo apoptosis in vivo and in vitro. Strikingly, transfer of the Npm1 mutation into a p53-null background rescued the apoptosis of Npm1-ablated HSCs and resulted in accelerated transformation to an aggressive and lethal form of acute myeloid leukemia. Our findings highlight the crucial role of NPM in stem cell biology and identify a new mechanism by which MDS can progress to leukemia. This has important therapeutic implications for de novo MDS as well as therapy-related MDS, which is known to rapidly evolve to leukemia with frequent loss or mutation of TRP53. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme

2019 ◽  
Author(s):  
Richard L Carpenedo ◽  
Sarah Y Kwon ◽  
R Matthew Tanner ◽  
Julien Yockell-Lelièvre ◽  
Chandarong Choey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Disease Modeling ◽  
Human Pluripotent Stem Cells ◽  
Endoderm Differentiation ◽  
Prolonged Differentiation ◽  
Defined Culture

SummaryHuman pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.

Preclinical Challenges and Clinical Target of Nanomaterials in Regenerative Medicine

2018 ◽  
pp. 1402-1423
Author(s):  
Martin Reinhardt ◽  
Shibashish Giri ◽  
Augustinus Bader
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Organ Engineering ◽  
Cell Therapies ◽  
Existing Problems ◽  
Present Generation

Currently, practical application of nanotechnological approaches and stem cell therapies remains a challenge in both preclinical and clinical settings. Many existing problems in tissue engineering to organ engineering have been solved by the combined approaches of nanotechnology and stem cell biology, but significant barriers remain. Details about the role of various types of nanomaterial in preclinical and clinical research have been reviewed elsewhere, but scant information exists about the influence of nanomaterials on stem cell biology. Herein, the authors highlight the current advances of nanotechnological approaches for expansion, differentiations, harvesting, labeling, imagining, tissue engineering, and organ engineering of different types of stem cells. The preclinical outcome of in vitro and in vivo animal experimentations along with some examples of clinical outcomes of nanomaterials on stem cell research is the main focus of this chapter. This book chapter might be an impetus for the present generation of young scientists to revolutionize the coming generation of effective human healthcare.

Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development

2002 ◽  
Vol 82 (4) ◽  
pp. 825-874 ◽  
Author(s):  
C. Yan Cheng ◽  
Dolores D. Mruk
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Biology ◽  
Cell Communication ◽  
Seminiferous Epithelium ◽  
Cell Junction ◽  
In Vivo Models ◽  
Blood Testis Barrier

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

scholarly journals Distinct Embryonic Origin and Injury Response of Resident Stem Cells in Craniofacial Muscles

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Cheng ◽  
Bing Shi ◽  
Jingtao Li
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Injury Response ◽  
Limb Muscles ◽  
Resident Stem Cells ◽  
Embryonic Origin

Craniofacial muscles emerge as a developmental novelty during the evolution from invertebrates to vertebrates, facilitating diversified modes of predation, feeding and communication. In contrast to the well-studied limb muscles, knowledge about craniofacial muscle stem cell biology has only recently starts to be gathered. Craniofacial muscles are distinct from their counterparts in other regions in terms of both their embryonic origin and their injury response. Compared with somite-derived limb muscles, pharyngeal arch-derived craniofacial muscles demonstrate delayed myofiber reconstitution and prolonged fibrosis during repair. The regeneration of muscle is orchestrated by a blended source of stem/progenitor cells, including myogenic muscle satellite cells (MuSCs), mesenchymal fibro-adipogenic progenitors (FAPs) and other interstitial progenitors. Limb muscles host MuSCs of the Pax3 lineage, and FAPs from the mesoderm, while craniofacial muscles have MuSCs of the Mesp1 lineage and FAPs from the ectoderm-derived neural crest. Both in vivo and in vitro data revealed distinct patterns of proliferation and differentiation in these craniofacial muscle stem/progenitor cells. Additionally, the proportion of cells of different embryonic origins changes throughout postnatal development in the craniofacial muscles, creating a more dynamic niche environment than in other muscles. In-depth comparative studies of the stem cell biology of craniofacial and limb muscles might inspire the development of novel therapeutics to improve the management of myopathic diseases. Based on the most up-to-date literature, we delineated the pivotal cell populations regulating craniofacial muscle repair and identified clues that might elucidate the distinct embryonic origin and injury response in craniofacial muscle cells.

scholarly journals Liver Organoids: Updates on Disease Modeling and Biomedical Applications

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 835
Author(s):  
Carmen Caiazza ◽  
Silvia Parisi ◽  
Massimiliano Caiazzo
Keyword(s):  
Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Low Complexity ◽  
In Vivo Models ◽  
Innovative Tool ◽  
Induced Pluripotent ◽  
Liver Organoids

Liver organoids are stem cell-derived 3D structures that are generated by liver differentiation signals in the presence of a supporting extracellular matrix. Liver organoids overcome low complexity grade of bidimensional culture and high costs of in vivo models thus representing a turning point for studying liver disease modeling. Liver organoids can be established from different sources as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), hepatoblasts and tissue-derived cells. This novel in vitro system represents an innovative tool to deeper understand the physiology and pathological mechanisms affecting the liver. In this review, we discuss the current advances in the field focusing on their application in modeling diseases, regenerative medicine and drug discovery.

scholarly journals C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation

2021 ◽  
Vol 8 ◽  
Author(s):  
Dominique Manikowski ◽  
Philipp Kastl ◽  
Sabine Schürmann ◽  
Kristina Ehring ◽  
Georg Steffes ◽  
...  
Keyword(s):  
Cell Biology ◽  
Stem Cell Biology ◽  
Wing Development ◽  
Alternative Possibility ◽  
Post Translational Modification ◽  
Peptide Tags ◽  
Hh Signaling ◽  
Outer Plasma Membrane

Hedgehog (Hh) morphogens are involved in embryonic development and stem cell biology and, if misregulated, can contribute to cancer. One important post-translational modification with profound impact on Hh biofunction is its C-terminal cholesteroylation during biosynthesis. The current hypothesis is that the cholesterol moiety is a decisive factor in Hh association with the outer plasma membrane leaflet of producing cells, cell-surface Hh multimerization, and its transport and signaling. Yet, it is not decided whether the cholesterol moiety is directly involved in all of these processes, because their functional interdependency raises the alternative possibility that the cholesterol initiates early processes directly and that these processes can then steer later stages of Hh signaling independent of the lipid. We generated variants of the C-terminal Hh peptide and observed that these cholesteroylated peptides variably impaired several post-translational processes in producing cells and Hh biofunction in Drosophila melanogaster eye and wing development. We also found that substantial Hh amounts separated from cholesteroylated peptide tags in vitro and in vivo and that tagged and untagged Hh variants lacking their C-cholesterol moieties remained bioactive. Our approach thus confirms that Hh cholesteroylation is essential during the early steps of Hh production and maturation but also suggests that it is dispensable for Hh signal reception at receiving cells.

Brain Tumor Stem Cells: Bringing Order to the Chaos of Brain Cancer

2008 ◽  
Vol 26 (17) ◽  
pp. 2916-2924 ◽  
Author(s):  
Peter B. Dirks
Keyword(s):  
Stem Cell ◽  
Brain Tumor ◽  
Cell Biology ◽  
In Vivo Models ◽  
Brain Tumor Cells ◽  
Brain Tumor Stem Cells ◽  
New Treatments ◽  
Key Pathways

Brain tumors are generally incurable cancers. Work from a number of laboratories strongly suggests that they are organized as a hierarchy based on a subset of cancer cells that have stem-cell properties. These cells have now been shown to be resistant to conventional therapy and responsive to differentiation therapy. New in vitro and in vivo models for interrogating brain tumor cells in stem-cell conditions have been developed that provide important new opportunities for elucidating the key pathways responsible for driving the proliferation of these cells. Continued application of the principles of stem-cell biology to the study of brain cancers is likely to continue to bring further important insight into these aggressive cancers, bringing new treatments and understanding of the origins.

Sign in / Sign up

Export Citation Format

Share Document