Abstract 1863: Cell-Based Therapy without Cell Transplantation: Tissue Engineering of an Acellular Matrix for the Recruitment of Endogenous Circulating Progenitor Cells
Bibliographic record
Abstract
Objectives: Following a cardiac event, circulating progenitor cells can home and engraft to sites of neovascularization, mediated in part by the adhesion molecule L-selectin; however, accumulation in the heart is low. We developed an acellular matrix containing the oligosac-charide sialyl Lewis X (sLe X ; 0.1mM), which binds L-selectin, in order to specifically enhance the engraftment of endogenous circulating progenitor cells. Methods: Adhesion and phenotype of CD133 + and CD34 + progenitor cells on sLe X -collagen or collagen matrix were assessed, and the role of L-selectin was characterized by blocking experiments. In animal work, a double hindlimb ischemic rat model was used (N=8): one hindlimb was injected with sLe X -collagen matrix, and the other with collagen matrix (200μl each). Rats underwent laser Doppler perfusion analysis at 0, 7 and 14 days post-operation. Two-week tissue was analysed by immunohistochemistry. Results: Cell adhesion was greater on sLe X -collagen matrix (9.0± 2.3%) as compared to collagen matrix (4.3± 2.6%), and was reduced by pre-incubating cells with sLe X (2.8± 1.3%) or anti-L-selectin (2.7± 1.0%; P< 0.001), demonstrating a role for sLe X in enhanced adhesion mediated by L-selectin binding. The proportion of CD133 + CD34 + L-selectin + cells was greater in the adherent population (8.1±3.4%) than in the non-adherent population (1.9±1.4%; P<0.001), indicating active recruitment of vasculogenic progenitors. Also, the sLe X -collagen matrix recruited 3.2±1.4 fold more CD133 + CD34 + L-selectin + cells than the collagen matrix (P<0.05). Rat ischemic hindlimbs treated with sLe X -collagen matrix recruited a greater number of CD133 + and c-kit + progenitor cells (3.0±1.0 and 2.1±1.0 fold, respectively; P<0.05) vs. collagen matrix treatment. The increase in progenitor cell engraftment was associated with a 3.8±1.1 fold greater intramuscular arteriole density (P<0.001) and with a 54% increase in hindlimb perfusion in sLe X -collagen matrix treated limbs (P<0.05). Conclusions: The sLe X -collagen matrix selectively enhances progenitor cell homing/engraftment mechanisms and endogenous cell-based tissue repair. Effectively, we have achieved progenitor cell-based therapy without the need for actual transplantation of cells.
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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".