Abstract 708: Platelet Derived Growth Factor-Beta Communication Axis is Critical for Mediating Pericyte-Endothelial Cell Interactions and Angiogenic Support in Combination Therapy of Human Umbilical Cord Perivascular Cells and Endothelial Progenitor Cells
Bibliographic record
Abstract
Introduction: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVC) have higher cardiovascular regenerative potential compared to older sources of MSC. We designed a cell combination therapy with FTM HUCPVC and endothelial progenitor cells (EPC) to enhance angiogenesis after MI. However, the mechanism of PVC-EPC interaction is unclear. Hypothesis: Platelet derived growth factor beta receptor (PDGFB-R) expression of HUCPVC mediates homing and integration with endothelial networks and required for supporting neovasculature. Methods: Expression of pericyte markers PDGFB-R and CD146 of xeno-free expanded (HPL 2.5%) FTM and term HUCPVC was analyzed by flow cytometry. PDGFB-driven trans-ECM migration was assessed by Corning Biocoat Invasion assay with 1-100 ng/ml PDGFB. siRNA for PDGFB-R, CD146 and scrambled control was used with lipofectamine for 72 hours. Silencing was confirmed by qPCR and flow cytometry. 10% HPL was used for PDGFB-R desensitization. HUCPVC of all treatment groups were co-cultured with EPC and rat aortic rings on Matrigel TM . Cell migration, endothelial adhesion and network properties were quantified. Statistics: one-way ANOVA N=5 Results: PDGFB-R and CD146 expression and endothelial network augmenting function of FTM HUCPVC was significantly higher than of term HUCPVC. PDGFB dependent migration of FTM HUCPVC was disabled by both ligand (<10%) and siRNA-based (<5%) downregulation of PDGFB-R. Fluorescence microscopy (24 h) showed limited homing and endothelial interactions of PDGFB-R-reduced FTM HUCPVC. PDGFB-R-reduced FTM HUCPVC had significantly decreased network growth and nodes ( p <0.0001) compared to control groups (day3). In EPC co-cultures, PDGFB-R-reduced FTM HUCPVC had limited endothelial interactions and coverage compared to control FTM HUCPVC. PDGFB-R-reduced FTM HUCPVC treated networks had significantly thinner ( p <0.001) and shorter tubules ( p <0.001) compared to control FTM HUCPVC groups. Down-regulation of C146 did not alter FTM HUCPVC pericyte properties. Conclusions: PDGFB-R is crucial for the homing and endothelial support of HUCPVC. This interaction is critical in vascular cell combination therapies and PDGFB-R expression can be a novel criterion for cardiovascular cell therapy.
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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) | 0.003 | 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".