Abstract 12299: Rejuvenation of the Bone Marrow-Derived Cardiac Resident Sca-1+ Stem Cell Subset Improved Healing of the Aged Heart
Bibliographic record
Abstract
Introduction: We previously reported that bone marrow (BM) reconstitution with young BM cells into aged recipients restored progenitors in both the BM and the myocardium and improved functional recovery post-injury. Here, our goal was to identify the specific cell type responsible for the improved cardiac regeneration and to restore that capacity in aged individuals after myocardial infarction (MI). Methods and Results: We reconstituted old mice with BM cells from young or old GFP+ mice to generate young chimeras and old chimeras. The number of BM-derived Sca-1+ progenitors homing to the heart was significantly greater in young chimeras compared to old ones (7.14±0.32/field for young vs 2.48±0.78/field for old, P<0.01, 5 high-powered fields/section, 3 sections/heart, 3 animals/group). We then separated Sca-1+ from Sca-1- young donor BM cells using magnetic cell sorting and transplanted them into lethally-irradiated old recipients to generate Sca-1+ and Sca-1- chimeras. Quantification by flow cytometry of heart tissue revealed: 1) the Sca-1+ chimeras had more BM-derived cells that co-expressed PDGFRβ (1.65±0.13% for Sca-1+ vs 0.52±0.09% for Sca-1-, P<0.05, n=4/group) and 2) the number of GFP+ PDGFRβ+ cells was greater in the Sca-1+ chimeric hearts than the Sca-1- chimeric hearts after MI (3.77±0.55% for Sca-1+ vs 0.85±0.106% for Sca-1-, P<0.05, n=3/group). The BM-derived cells that homed to the heart in the Sca-1+ chimeras actively proliferated, stimulated proliferation of the host’s aged progenitors and improved ventricular function after MI. BM chimerism with Sca-1+ cells in aged mice restored the regenerative capability of cardiac resident progenitors and improved functional healing of the aged heart. Conclusions: BM Sca-1+ cells that homed to the heart in aged recipients proliferated and stimulated the propagation of host aged progenitor cells post-MI. This improved regeneration involved activation of the PDGFRβ/Akt/p27Kip1 signaling pathway. The number of BM-derived Sca-1+ progenitor cells in the aged myocardium was the major determinant for successful cardiac functional recovery. Restoration of the Sca-1 subset of stem cells by BM reconstitution improved cardiac repair and prevented heart failure.
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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) | 0.001 | 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) | 0.006 | 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".