Single-cell microencapsulation improves lung retention of endothelial colony forming cells after intravascular delivery and unmasks therapeutic benefit in severe pulmonary arterial hypertension
Bibliographic record
Abstract
Abstract Background Pulmonary arterial hypertension (PAH) is triggered by pulmonary vascular endothelial cell apoptosis and microvascular loss; therefore, therapies that can regenerate lost vasculature may offer therapeutic benefit. Endothelial colony forming cells (ECFCs) can directly repair damaged blood vessels and may have therapeutic potential for the treatment of PAH. However, poor retention of ECFCs in the lungs following intravenous delivery greatly limits their therapeutic application. Therefore, we studied whether cellular microencapsulation could enhance ECFCs viability and retention in the lung after systemic delivery and improve therapeutic efficacy of ECFCs in a rat monocrotaline (MCT) PAH model. Methods ECFCs were encapsulated by vortex-emulsion using various concentrations of agarose, and capsule size and initial cell viability were assessed. Encapsulated and free ECFCs were transduced with luciferase and administered to Sprague-Dawley rats three days after injection of MCT. ECFCs were tracked in vivo by bioluminescence imaging (BLI) to assess cell persistence and bio-distribution. At end-study, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were assessed for therapeutic efficacy. Results Microgel encapsulation using 3.5% agarose improved cells survival and supported cell migration from capsules. At 15 minutes after delivery, BLI radiance were similar for free and microencapsulated ECFCs; however, only encapsulated cells could be detected by BLI at 4 and 24 hours. Transplantation of microencapsulated ECFCs led to significant improvement in RVSP three weeks after delivery compared to non-encapsulated ECFCs. Conclusion Together, microencapsulation increased retention of ECFCs within the lungs. Furthermore, even a modest increase in ECFCs persistence over 24 hours can provide an important therapeutic benefit in the rat MCT model of PAH.
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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) | 0.000 | 0.000 |
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".