Abstract 11927: Paracrine Engineering of Human Cardiac Stem Cells to Over-Express Stromal Cell-Derived Factor 1α Enhances Post-Ischemic Cardiac Repair
Bibliographic record
Abstract
Introduction: First generation cardiac stem cell (CSC) products provide indirect cardiac repair but variably produce key cardioprotective cytokines (such as stromal-cell derived factor 1α (SDF1α)) which opens the prospect of maximizing up-front paracrine-mediated repair. Methods/Results: The mesenchymal sub-population within human CSCs underwent lentiviral (lv) mediated gene transfer of SDF1α. Cytokine array profiling revealed that SDF1α over-expression prevented lv-mediated “loss of cytokines” through autocrine stimulation of the 47±4% CXCR4+ CSCs. SDF1α enhanced angiogenesis and stem cell recruitment while priming CSCs to readily adopt a cardiac identity. As compared to injection with unmodified CSCs, transplant of SDF1α transduced CSCs into NOD SCID mice improved myocardial function (4 week LVEF: 39±2 vs. 33±1%; p≤0.05) and angiogenesis (4±0.7 vs. 2±0.5 isolectin b4+ve vessels/field; p≤0.05) while reducing scarring (4.0±0.2 vs. 5.8±0.7%, p≤0.05). Infarct, infarct border and off-target regions demonstrated greater SDF1α content (7 days post injection: 51±12, 7±1 and 16±5 fold increased vs. unmodified CSCs, p≤0.05) which paralleled reductions in myocyte apoptosis (i.e., increased Bcl-2 to Bax ratio disparity) but did not influence long-term CSC engraftment or the fate of transplanted cells. BrdU pulsing revealed that transplantation of SDF1α transduced CSCs increased the generation of new myocytes (BrdU+/TnT+; 1.4±0.1 fold increase vs. unmodified CSCs; p=0.02). A murine sex mismatch bone marrow transplant model confirmed that transplant of unmodified CSCs did not increase recruitment of bone marrow cells (vs. PBS injection alone) while transplant of SDF1α transduced CSCs increased bone marrow cell recruitment by 2.3±0.5 and 1.5±0.3 fold at 7 (p≤0.05) and 14 (p=0.08) days after CSC injection as compared to transplant of unmodified CSCs. Conclusions: Paracrine engineering of human CSCs to over-express SDF1α enhances recruitment of endogenous stem cells, new myocyte/vessel formation and salvage of reversibly damaged myocardium to enhance cardiac repair after experimental MI.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".