Injectable, cryopreservable mesenchymal stromal cell-loaded microbeads for pro-angiogenic therapy: in vitro proof-of-concept
Bibliographic record
Abstract
Abstract Despite their recognized potential for ischemic tissue repair, the clinical use of human mesenchymal stromal cells (hMSC) is limited by the poor viability of cells after injection and the variability of their paracrine function. In this study, we show how the choice of biomaterial scaffolds and the addition of cell preconditioning treatment can address these limitations and establish a proof-of-concept for cryopreservable hMSC-loaded microbeads. Injectable microbeads in chitosan, chitosan–gelatin, and alginate were produced using stirred emulsification to obtain a similar volume moment mean diameter (D[4,3] ∼ 500 µm). Cell viability was determined through live/dead assays, and vascular endothelial growth factor (VEGF) release was measured by ELISA. Proangiogenic function was studied by measuring the wound closure velocity of human umbilical vein endothelial cells (HUVEC) co-cultured with MSC-loaded microbeads. The effect of freeze–thawing on microbeads morphology, porosity, injectability and encapsulated MSC was also studied. hMSC-loaded chitosan-based microbeads were found to release 11-fold more VEGF than alginate microbeads ( p < 0.0001) and chitosan–gelatin was chosen for further studies because it presented the best cell viability. Preconditioning with celastrol significantly enhanced the viability (1.12-fold) and VEGF release (1.40-fold) of MSC-loaded in chitosan–gelatin microbeads, as well as their proangiogenic paracrine function (1.2-fold; p < 0.05). In addition, preconditioning significantly enhanced the viability of hMSC after 1 and 3 d in low-serum medium after cryopreservation ( p < 0.05). Cryopreserved hMSC-loaded microbeads maintained their mechanical properties, were easily injectable through a 23G needle, and kept their paracrine function, enhancing the proliferation and migration of scratched HUVEC. This study shows the advantage of chitosan as a scaffold material and concludes that chitosan–gelatin microbeads with celastrol-preconditioned cells form a promising off-the-shelf, cryopreservable allogenic MSC product. In vivo testing is required to confirm their potential in treating ischemic diseases or other clinical applications.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 | 0.000 |
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 teacher head, 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".