(149) PD.SPHERE, a Novel Three-dimension Cellular Model for Peyronie’s Disease via ‘Microgravity’ Condition: The New Era of in vitro Cell Culture-based Model for PD
Bibliographic record
Abstract
Abstract Introduction Peyronie's disease (PD) is a common problem that affects 4-13% of the male population and results in a significant decline in patient and partner quality of life. Currently, in vitro monolayer fibroblast culture and animal models are actively used to study pathogenesis and treatments. However, both models are not a great pathophysiological representative for human PD due to the lack of cellular architecture and limited insight into the PD mechanism. Objective We aimed to develop a three-dimensional (3D) cellular model to reveal the PD pathogenesis mechanism and perhaps use this model as a treatment screening tool. Methods Human PD fibroblasts isolated from PD patients during surgery were cultured in various non-adhesive culture plates under the 'microgravity' condition. Complete media (DMEM+10% FBS+2mM L-glutamine) with and without TGF-β supplement was used to optimize the conditions for the PD.SPHERE, a 3D cell culture model of PD fibroblasts. Molecular probes against nucleus, actin, vimentin (VIM) and smooth muscle actin (SMA) were used to study the morphology and expression of molecular markers. Confocal-microscopic analyses were performed to obtain the morphological snapshots of and molecular data of the PD.SPHERE. Results We successfully developed a 3D cell culture (spheroid) model from human PD fibroblasts with our defined conditions. The PD spheroids were formed individually in each vessel of a 96-well plate coated with a non-adhesive substance. A PD.SPHERE was made in each well in a 96-well plate from three different individuals. Moreover, the size and circularity of spheroids were consistent across the plate. Although TGF-β supplemented condition significantly increased the cell division capability of the PD fibroblasts in the monolayer model, this supplementation was not necessary for our 3D model since TGF-β did not significantly increase the size and circularity of the 3D model. Despite the spheroids' increases in cell density over the culturing period, TGF-β did not affect the cell density in the 3D-cellular structure. Throughout the PD.SPHERE architecture, it also expressed SMA and VIM, the intracellular skeletal markers. Conclusions In conclusion, our model is consistent, reproducible and morphologically relevant to a PD plaque. Our model also demonstrates that we have the potential to produce high throughput treatment screening platforms for PD. Additionally, the PD.SPHERE platform is personalized and customizable to the specific individual; thus, our model indicated the potential to develop this platform for personalized treatment planning. However, signature gene expression and physiological and immunological information (i.e., collagen production, extracellular matrix organization, cellular expression of tight junctions, chemokines, and cytokines) should be further collected to verify the pathophysiological, immunological and treatment response for this model. Disclosure No
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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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".