Abstract 1804: The role of adipose derived stromal cells for reversal of radiation fibrosis
Bibliographic record
Abstract
Abstract Hypothesis: Up to 70% of patients after radiotherapy develop radiation fibrosis (RF), an irreversible scarring of normal tissue resulting in functional morbidity and increased risk of surgical complications. Adipose-derived stromal cells (ADSCs) have been used effectively for the treatment of complex wounds in animal models and clinical trials. We hypothesize that ADSCs may reverse RF by repopulating mesenchymal precursor cells and by providing angiogenic, anti-inflammatory, and matrix remodeling factors. Methods: A RF animal model was developed and ADSC isolation was confirmed by immunophenotype and differentiation assay. GFP and luciferase labelled ADSCs were used to assess biodistribution after transplantation. To determine the therapeutic effect of ADSC transplantation for RF, we assessed functional changes to leg contracture, oxygen saturation and perfusion and molecular changes to inflammation, vascularization, and matrix remodeling. To determine the mechanism of ADSC-mediated fibrosis reversal, we assessed transcriptomic and epigenetic changes to RF tissue. Results: A RF model was created by radiating the hind limb of C3H mice. This model showed a dose dependent leg contracture and histological findings of fibrosis. We confirmed the immunophenotype of isolated ADSC and their ability to differentiate into adipogenic, chondrogenic, and osteogenic lineages. ADSC transplantation showed a statistically significant trend towards improved leg contracture (2-way ANOVA, p<0.05). Biodistribution studies confirmed the presence of ADSCs in the subdermis of RF tissue with persistence for at least 18 days post-transplantation. Preliminary RNA-seq analysis using unsupervised hierarchical clustering showed ADSC treated radiation tissue was more similar to normal tissue than control. In depth RNA-seq data analysis is underway. Conclusions: ADSC transplantation may be an effective treatment for the reversal of radiation fibrosis. As cancer survivorship increases, the prevalence of radiation fibrosis will rise and necessitate increased focus on effective treatment strategies for this condition. Citation Format: Xiao Zhao, Ju Hee Lee, Kenneth Yip, Laurie Ailles, Fei-Fei Liu. The role of adipose derived stromal cells for reversal of radiation fibrosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1804. doi:10.1158/1538-7445.AM2015-1804
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".