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Culturing precision-cut human prostate slices as an in vitro model of prostate pathobiology
A R Parrish1, K Sallam, D W Nyman
1Department of Medical Pharmacology, Texas A&M University, College Station, USA.
Abstract:
Due to the complex morphology of the prostate, it was hypothesized that precision-cut tissue slices from human prostate would provide a unique in vitro model. Precision-cut slices were generated from zones of human prostate and their viability was assessed under conditions of different media for up to 120 h. Slices were also exposed to several concentrations of CdCI2, which was used as a model toxicant. Maintenance of both stromal and epithelial cells was noted; however, there was a gradual loss of luminal epithelial cells when the medium was not supplemented with dihydrotestosterone (DHT). Minimal leakage of lactate dehydrogenase occurred throughout the incubation. Prostate-specific antigen (PSA) was detected in the medium at all time points, although the rates of secretion fell over time. There was a loss of PSA-positive cells when the medium was not supplemented with DHT, consistent with a loss of luminal cells, whereas PSA-positive cells were maintained in the DHT-supplemented media. A proliferation of basal cells was observed in the presence of media containing 10% fetal bovine serum. Exposure of slices to CdCl2 demonstrated a dose-response effect ranging from proliferation to complete cellular necrosis. Given the retention of stromal-epithelial interactions and the use of acquired human tissue, prostate slices represent a unique in vitro model for investigating human prostate pathobiology.
Insights
Human prostate tissue slices offer a novel in vitro model for studying prostate diseases. Dihydrotestosterone (DHT) is crucial for maintaining luminal epithelial cells and prostate-specific antigen (PSA) secretion in these precision-cut slices.
Area of Science:
- Urology
- Cell Biology
- Toxicology
Background:
- The prostate's complex structure necessitates advanced in vitro models for research.
- Understanding prostate pathobiology requires models that retain stromal-epithelial interactions.
Purpose of the Study:
- To evaluate precision-cut human prostate tissue slices as a unique in vitro model.
- To assess the viability and key markers of prostate tissue slices under various conditions.
- To investigate the effects of dihydrotestosterone (DHT) and a model toxicant (CdCl2) on prostate slices.
Main Methods:
- Generating precision-cut slices from different zones of human prostate tissue.
- Assessing cell viability and morphology over 120 hours in different media.
- Measuring lactate dehydrogenase leakage and prostate-specific antigen (PSA) secretion.
- Exposing slices to varying concentrations of cadmium chloride (CdCl2).
Main Results:
- Prostate slices maintained both stromal and epithelial cells, with DHT crucial for luminal cell and PSA-positive cell survival.
- Minimal lactate dehydrogenase leakage indicated good tissue integrity.
- PSA secretion was detected, though it decreased over time.
- CdCl2 exposure showed a dose-dependent toxic effect, from proliferation to necrosis.
- Basal cell proliferation occurred in media with 10% fetal bovine serum.
Conclusions:
- Precision-cut human prostate slices represent a valuable in vitro model due to retained stromal-epithelial interactions.
- This model is suitable for studying human prostate pathobiology and toxicological effects.
- The necessity of DHT for maintaining specific cell populations and functions was confirmed.
