4 Development of a humanized, functional, tissue engineered, in vitro model of healthy myocardium
Bibliographic record
Abstract
Introduction Cardiac research over the past decade has significantly improved our understanding of the interaction between cardiomyocytes and immune cells, illuminating the importance of cardiac resident macrophages (CRMs) in maintaining homeostasis within the myocardium. In particular, macrophages in the heart perform a number of critical functions such as facilitating electrical conduction, capture and elimination of cardiac exophers and routine immunosurveillance.1 Here, we aim to fabricate a tissue engineered model of healthy myocardium, integrating an innate immune response for patient-specific drug screening, regenerative medicine and drug discovery applications. Methods iPSCs were differentiated to obtain macrophages (iMacs) and cardiomyocytes (iCMs). To understand how macrophages respond to a cardiac environment, iMacs were exposed to distinct cardiac cues, such as conditioned media from iCMs, co-culture with iCMs and electrical stimulation. Analyses were performed using flow cytometry, qRT-PCR and immunofluorescence imaging. Finally, an engineered heart tissue (EHT) model was developed using type I collagen and Matrigel to fabricate 3D models of the myocardium, incorporating an innate immune response. Results The iMacs that were generated were found to have a resident macrophage phenotype, with ability to perform phagocytosis as well as polarize to become classically and alternatively activated macrophages. iMacs displayed unique gene expression profiles when in culture with iCM conditioned media as well as in co-culture with iCMs. Interestingly, when in co-culture with iCMs, iMacs expressed CRM-specific genes, as well as cardiac developmental genes. Additionally, iCMs in co-culture with iMacs displayed an elongated morphology, with an upregulation in maturation markers. Furthermore, iMacs were also found to electrically couple with iCMs and facilitate synchronous beating, demonstrating great potential to improve iCM function in vitro. Reference Suku M, Forrester L, Biggs M, Monaghan MG. Resident macrophages and their potential in cardiac tissue engineering. Tissue Eng Part B Rev. 2022.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".