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Record W190923160

The influence of the extracellular matrix on cell behaviour

2009· dissertation· en· W190923160 on OpenAlex
Michael J. Cooke

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueDurham e-Theses (Durham University) · 2009
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsnot available
FundersUniversity of Toronto
KeywordsExtracellular matrixStem cellBiologyCell biologyInduced pluripotent stem cellMatrigelEmbryonic stem cellTransplantationTeratomaCellular differentiationImmunologyCellPathologyMedicineBiochemistryInternal medicine
DOInot available

Abstract

fetched live from OpenAlex

Stem cell research has raised great interest in the scientific community as it has the potential to form multiple cell types and it is believed they hold the key to curing many diseases. However, there is a need for better understanding of how to control these cells and further research investigating methods for controlling and directing these cells is required. Pluripotent stem cells transplanted into immune-deficient mice 'spontaneously’ differentiate and proliferate to form a complex mass of differentiated and undifferentiated cells, teratomas - teratoma assay. Such tumours are generally haphazard in their organisation however; they do contain some structures similar to those observed in the embryo. Teratoma formation is a useful model to explore the developmental potential of stem cells and study aspects of tissue development. Examination of how the anatomical location into which human pluripotent stem cells are grafted influences their growth in situ allows investigation of how these cells are affected by different areas within the body: cells grafted into the liver rapidly produce large tumours containing predominantly immature cells whereas, subcutaneous implants were significantly slower growing and formed tumours composed of differentiated tissues. These different growth patterns indicate how environmental cues within the niche affect stem cell behaviour. One factor which contributes to the maintenance of a niche is the extracellular matrix (ECM). To investigate how endogenous ECM affects teratoma behaviour, co-transplantation is carried out with stem cells and ECM components. The ECM extract Matrigel™ dramatically increased the success rate of teratoma formation and size with no detectable affect on teratoma composition when compared to controls and removal of the growth factors from the co-transplanted ECM extract had no effect on teratoma success rate, growth rate, or composition. To study the effects of the ECM in vitro, components of the ECM are often used topcoat glass or plastic surfaces to enhance cell attachment in vitro. Fragments of ECM molecules can be immobilised on surfaces in order to mimic the effects seen by whole molecules. In this study a novel technology developed by Oria Protein Technologies for the immobilisation of peptide sequences from ECM proteins is evaluated. By examining: the adherence of cultured PC 12; neurite outgrowth from PC 12 cells; and neuronal differentiation of neural stem/progenitor cells (NSPCs) it is shown that peptides from collagen I, collagen IV, fibronectin and laminin can mimic surfaces coated with ECM proteins. Collectively, this data demonstrates that peptides from ECM proteins can be immobilised in functional fashion to control cell behaviour. Surfaces with adsorbed proteins and biomimetic surfaces presenting peptide motifs from ECM proteins are used to investigate and explain observations from in vivo teratoma experiments. In vivo, Matrigel™ increases the gene expression of the pluripotent stem cell marker Oct4, increasing the pluripotent cell percentage and thus increases the likelihood of teratoma formation. In vitro, Matrigel™ also increases the gene expression of the proliferative marker Ki67, indicating that large teratomas from by the co-transplantation of stem cells with Matrigel™ could be due to increased cell proliferation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.297
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.232
Teacher spread0.226 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it