Psoriasis is a skin disorder characterized by epidermal hyperplasia, hyperkeratosis, and inflammation. The treatments currently available on the market only improve patients’ quality of life and are associated with undesirable side effects. Thus, research leading to the development of new, effective, and safer therapeutic agents is still relevant. Populus balsamifera L. buds were used traditionally by Native Americans to treat various skin pathologies such as eczema and psoriasis. In this study, the antipsoriatic activities of dihydrochalcone derivatives from Populus balsamifera L. buds, known as balsacones, were investigated. The experiments were performed in vitro using a psoriatic skin substitute model. Also, anti-inflammatory and antioxidant activities were investigated. The tested balsacones showed promising antipsoriatic properties by slowing down cell growth and by regulating the expression of involucrin, loricrin, and Ki67 better than methotrexate in psoriatic substitutes. All five tested compounds could be an effective topical treatment for psoriasis, with promising anti-inflammatory and antioxidant actions that may contribute to clinical improvement in patients with psoriasis.

BackgroundInadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of compound effects. Consequently, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcomes.MethodsThe current research aims to compare the impact of using serum-free medium instead of complete culture medium during the last step of psoriatic skin substitute reconstruction. Skin substitutes were produced according to the self-assembly approach.ResultsSerum-free conditions have no negative impact on the reconstruction of healthy or psoriatic skin substitutes presented in this study regarding their macroscopic or histological appearances. ATR-FTIR results showed no significant differences in the CH2 bands between psoriatic substitutes cultured with or without serum, thus suggesting that serum deprivation did not have a negative impact on the lipid organization of their stratum corneum. Serum deprivation could even lead to a better organization of healthy skin substitute lipids. Percutaneous analyses demonstrated that psoriatic substitutes cultured in serum-free conditions showed a higher permeability to hydrocortisone compared to controls, while no significant differences in benzoic acid and caffeine penetration profiles were observed.ConclusionsResults obtained with this 3D-psoriatic skin substitute demonstrate the potential and versatility of the model. It could offer good prediction of drug related toxicities at preclinical stages performed in order to avoid unexpected and costly findings in the clinic.General significanceTogether, these findings offer a new approach for one of the most important challenges of the 21st century, namely, prediction of drug toxicity.

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Tissue engineering of the skin is used for various applications. However, to develop treatments for skin pathologies such as psoriasis, robust pathological skin models are needed. The purpose of the work presented in this chapter was to optimize the production of more reproducible psoriatic skin substitutes by modifying the original self-assembly method. Substitutes were produced according to the self-assembly method partially modified. The culture flasks of 25 cm 2 were replaced by 6-well and 12-well plates. Fibroblasts were cultured in 6-well and 12-well plates with ascorbic acid until they form manipulable sheets, which were superimposed and incubated for 7 days to form a dermal layer. Afterwards, keratinocytes were seeded on the dermal layer forming an epidermal layer. Then, the substitutes were raised to the air-liquid interface and cultured 21 days before being analyzed. Analyses demonstrated that psoriatic substitutes have a significantly thicker epidermis than healthy substitutes and the persistence of nuclear structures in corneocytes, with original and both modified methods. Immunofluorescence markers such as filaggrin, loricrin, and keratin 14 have confirmed these results. However, some differences were observed in substitutes produced with 12-well plates. Modifications made to the original method for the production of psoriatic substitutes are effective and lead to highly reproducible substitutes more suitable for pharmacological testing.

Despite the emergence of serum-free media for cell culture, the use of serum to supplement the culture media is still essential in order to produce engineered urologic tissues using the self-assembly approach, not only for the stromal compartment but also for the uroepithelium. Effects of sera on thickness of these two compartments were measured and quality of the epithelial differentiation was evaluated. For bladder mucosa substitute reconstruction, the use of postnatal sera failed to produce an adequate uroepithelium whereas the fetal sera supplementation did. Postnatal sera also provided thinner stromal compartments than the one obtained using fetal sera, no matter if the fibroblasts from healthy or psoriatic donors were used to reconstruct human skin substitutes.