Bibliographic record
Abstract
Mesenchymal stromal cells (MSCs) are increasingly used in human cell therapy protocols. Two major issues, however, have yet to be addressed with this intriguing cell population: the likelihood of true transdifferentiation and isolation of MSC stem cells. To date, neither has been convincingly demonstrated. We have attempted to address both issues here. The demonstration of self‐renewal and differentiation ‐ key criteria for stem cell characteristics ‐ have yet to be accomplished. To address this issue, we rigorously generated true clones from the highly proliferative population of MSCs derived from non‐transformed human umbilical cord perivascular cells (HUCPVCs) that share the properties and immunophenotype of bone marrow‐derived MSCs. We demonstrated a hierarchy of differentiation potential along adipocytic, osteogenic, chondrogenic, myogenic and fibroblastic lineages. Future studies will be aimed at characterizing clones for the regeneration of specific tissues. To address the issue of transdifferentiation, we employed a novel in vitro system in which embryonic rat cardiomyocytes are co‐cultured with adult murine MSCs derived from transgenic animals carrying the cardiac‐specific myosin heavy chain promoter driving green fluorescence protein (GFP). We found that some cells expressed GFP and, additionally, had acquired several cardiac‐specific markers but nevertheless had retained all previously assayed MSC determinants, suggesting the generation of a unique cell population that we also showed had not arisen from cell fusion. Furthermore, electrophysiological studies revealed that these unique GFP+ cells do not generate action potentials or ionic currents typical of cardiomyocytes, indicating that the cells are functionally, stromal and not cardiomyocytes. The presence of this population in vivo was confirmed in studies with a murine experimental acute myocardial infarction model. The implications of these findings on the nature of tissue regeneration with exogenous MSCs will be discussed in detail.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".