Abstract P1065: Primitive Macrophages Enhance The Function Of Bioengineered Human Cardiac Microtissues
Bibliographic record
Abstract
Human cardiac bioengineering has traditionally focused on cardiomyocyte differentiation and maturation. Unlike normal cardiac growth in the native human heart, human pluripotent stem cell (hPSC)- derived cardiomyocytes are typically grown in the absence of key supportive populations, which may negatively impact function due to a failure to recreate complex multicellular environments. In vivo murine studies have demonstrated that embryonic-derived resident cardiac macrophages promote neonatal cardiac regeneration, yet macrophages have not been incorporated in cardiac bioengineering approaches. We hypothesized that inclusion of human embryonic stem cell derived primitive macrophages (hESC-macrophages) into bioengineered human cardiac microtissues (“Biowires”) would improve cardiomyocyte functional properties. We found that addition of hESC-macrophages into Biowires led to enhanced contractile force, improved relaxation, reduced excitation threshold, increased maximum capture rate, and increased conduction velocity that mechanistically was correlated with improved calcium cycling, indicating hESC-macrophages improve a broad range of electromechanical properties. Moreover, hESC-macrophages enhanced microtissue function across cardiomyocyte cell sources and bioengineering platforms (Experimental N=6 independent cellular differentiations across 2 different platforms). These changes occurred in the absence of significant transcriptional shifts in cardiomyocytes. Rather, Biowires with hESC-macrophages had reduced mitochondrial DNA release, oxidative stress and cytotoxicity in the very early phases of tissue formation, thereby promoting a favorable environment for cardiac microtissue development. In conclusion, these data reveal a previously unappreciated, yet major beneficial role for macrophages specifically in human cardiac tissue engineering. In general, bioengineering human tissue continues to be a major research focus, and our data argue that inclusion of yolk sac-derived macrophages may improve early microtissue formation and modeling in vitro , and could enhance cell delivery approaches in vivo .
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".