SDF-1-CXCR4 and HGF-c-met Axes Regulate Mobilization/Recruitment to Injured Tissue of Human Mesenchymal Stem Cells.
Bibliographic record
Abstract
Abstract Human mesenchymal stem cells (MSC) have been shown to egress from the bone marrow (BM), circulate in peripheral blood (PB) and differentiate into many cell types, making them attractive as a potential therapeutic tool for organ/tissue regeneration. However the signals required for their mobilization into PB and their recruitment into injured sites are not fully understood. We previously reported that stromal-derived factor (SDF)-1 and hepatocyte growth factor (HGF) are upregulated at sites of tissue damage (Cancer Research2003; 63:7926; Leukemia2004; 18:29) and in this study we examined whether these factors mediate the migration of MSC. We investigated (i) the expression in MSC of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF, (ii) whether they are functional after early and late passages (using a chemotaxis assay across fibronectin and the reconstituted basement membrane Matrigel), and (iii) whether MSC express matrix metalloproteinases (MMPs) known to facilitate mobilization and homing of stem cells. MSC were derived from human bone marrow (BM) or cord blood (CB) and maintained for up to 18 passages (in IMDM and 10–20% FCS) with monitoring of markers for cardiac (Nkx2.5/Csx, GATA-4 and MEF2-C), skeletal muscle (Myo-D and myogenin) and endothelial cells (VE-cadherin and VEGFR-2). We found that (i) CB and BM MSC strongly express CXCR4 and c-met transcripts for up to 15 passages, (ii) these receptors are functional as the MSC cells were chemotactic and chemoinvasive (across Matrigel) towards gradients of SDF-1 (100 ng/mL) or HGF (40 ng/mL), and (iii) CB and BM MSC express MMP-2 mRNA and secrete both latent and active forms of MMP-2. Moreover, we found that CB and BM MSC expressed mRNA for all three cardiac markers and the endothelial marker VE-cadherin, indicating their potential for heart regeneration. In conclusion, these results indicate that the SDF-1-CXCR4 and HGF-c-met axes are important signaling pathways in MSC mobilization and their trafficking in PB, and could be involved in recruitment of MSC to damaged tissues (e.g., myocardium).
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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) | 0.002 | 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".