Primary cell culture model

Reinhardt CA (1993) Neurodevelopmental toxicity in vitro Primary cell culture models for screening and risk assessment. Reprod Toxicol, 7(Suppl 1) 165-170. 

The primary cell culture model is a more valid model for the study of absorption and transport processes of a drug via the pulmonary route. It provides a tight epithelial barrier with morphological and functional properties resembling those of the in-vivo condition. Primary alveolar epithelial cells from rats [39], rabbits [40] and humans [41] which display morphological and biochemical characteristics similar to the native epithelium have been isolated and can be used for drug transport studies. 

In summary, primary cultures of hPT cells represent a unique and highly relevant experimental model for the study of drug metabolism, transport, mechanism of action, and nephrotoxicity. Although there exist the usual cautions with primary cell culture models, and cell culture models in general, once technique is mastered and appropriate conditions are used to minimize potential issues with the culture process, the primary hPT cells have numerous advantages over other models for obtaining information about drug action that is directly relevant to humans. 

In a primary cell culture model from embryonic day 18 rat brains in which striatal neurones un-... 

In vitro cell culture models of human nasal epithelium based on primary culture technologies have proven to be extremely useful for mechanistic studies of nasal epithelial permeability and drug absorption [13]. However, efforts... 

In Vitro Primary and Passaged Cell Culture Models... 

For in vitro toxicity studies and assessment of the barrier function, drug transport, cell physiology, and metabolism as well as the development of delivery systems, cell culture models provide powerful systems for scientific research. As the corneal epithelium is the main barrier for ocular penetration, various corneal epithelial cell cultures were established besides the corneal constructs that mimic the whole cornea and serve as reductionist models for the ocular barrier. In general, two types of cell culture models are available primary cell cultures and immortalized, continuous cell lines. 

Different hypotheses have been raised to explain these purported beneficial effects. Ono et al. have shown that the neuroprotective effects of various polyphenols (e.g., myricetin, morin, and, to a lesser extent, quercetin) may be due to their ability to inhibit amyloid fibrils and to destabilize fibrilized forms of Ap,20 suggesting that they could be considered as new therapeutic agents for the treatment of AP-associated diseases.21 Resveratrol, a red-wine polyphenol, has been proposed to promote the intracellular degradation of Ap by a proteasome-dependent and secretase-independent activity.22 Based on these findings, we compared the effects of polyphenols found in teas and red wine, using the model of AP-induced toxicity in rat hippocampal primary cell cultures. 

However, demands for non-human tests are still there, and several challenges have been tried, based on cell culture models or animal models, for measuring protein release as an indicator of irritancy Finally, the systemic toxicity of additives is a common concern with any route of administration. The nasal absorption of the additives, as well as of the primary ingredients, should be carefully assessed. 

Whole animal models and traditional cell culture models have been the primary mode of validation for this purpose. However, animal models are subject to significant expense, lengthy experiments, ethical issues, and it is often difficult to extrapolate results from animals directly to effects on human beings. Results from traditional in vitro cell culture are of limited usefulness due to the difficulty sustaining in vivo functions of primary cells as an isolated, static system [95],... 

Cell culture models to evaluate the pulmonary fate of inhaled drugs have not been used extensively for characterizing inhalation drugs. However, this technique is promising and will be briefly discussed. This section focuses on airway and alveolar epithelial models using cell lines and primary cell culture methods. 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

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