Clinical Trials with Mesenchymal Stem Cell Therapies for Osteoarthritis: Challenges in the Regeneration of Articular Cartilage.

Osteoarthritis (OA) is a whole-joint disease primarily characterized by the deterioration of hyaline cartilage. Current treatments include microfracture and chondrocyte implantation as early surgical strategies that can be combined with scaffolds to repair osteochondral lesions; however, intra-articular (IA) injections or implantations of mesenchymal stem cells (MSCs) are new approaches that have presented encouraging therapeutic results in animal models and humans. We critically reviewed clinical trials with MSC therapies for OA, focusing on their effectiveness, quality, and outcomes in the regeneration of articular cartilage. Several sources of autologous or allogeneic MSCs were used in the clinical trials. Minor adverse events were generally reported, indicating that IA applications of MSCs are potentially safe. The evaluation of articular cartilage regeneration in human clinical trials is challenging, particularly in the inflammatory environment of osteoarthritic joints. Our findings indicate that IA injections of MSCs are efficacious in the treatment of OA and the regeneration of cartilage, but that they may be insufficient for the full repair of articular cartilage defects. The possible interference of clinical and quality variables in the outcomes suggests that robust clinical trials are still necessary for generating reliable evidence with which to support these treatments. We suggest that the administration of just-sufficient doses of viable cells in appropriate regimens is critical to achieve effective and durable effects. In terms of future perspectives, genetic modification, complex products with extracellular vesicles derived from MSCs, cell encapsulation in hydrogels, and 3D bioprinted tissue engineering are promising approaches with which to improve MSC therapies for OA.

Biotechnological Assessment of Culture Conditions on the Stress-Induced Carotenoid Production of Dunaliella salina and Growth Kinetics of Chlorophyceae Microalgae Strains

Abstract Microalgae are potential sources of a wide range of bioproducts. It is essential to choose the proper microalgae strain and culture condition to achieve an efficient production. The production yield of carotenoids by Dunaliella salina under the stress-induced culture conditions of nitrogen deprivation and excessive light intensity was evaluated. Also, a survey at laboratorial scale of the growth kinetics under different culture conditions of photoperiod, aeration, and agitation was performed for the seven species of green microalgae Ankistrodesmus fusiformis, Chlamydocapsa bacillus, Desmodesmus brasiliensis, Kirchneriella lunaris, Pseudokirchneriella subcapitata, and Scenedesmus obliquus. As a result, aeration of atmospheric air is enough to improve the growth kinetics of the seven species studied. Production of carotenoids was enhanced under stress by excessive light intensity. Although D. salina does not grow effectively under nitrogen deprivation, this stress condition may be used to quickly stimulate carotenoid production once the culture reaches a high cellular population.

Analyzing the toxicity of bisphenol-A to microalgae for ecotoxicological applications.

Bisphenol-A (BPA) is a chemical used in the production of polycarbonate plastic and epoxy resins that may be related to the occurrence of human endocrine disorders. The present study aims to indicate a microalgae for use in ecotoxicological tests concerning BPA contamination of aquatic environments by analyzing its toxicity for the freshwater species Pseudokirchneriella subcapitata, and the two marine species Tetraselmis chuii and Skeletonema costatum. The standardization of the test involved determination of suitable nominal concentrations of BPA and the most appropriate species for use as biomarkers. S. costatum and P. subcapitata demonstrated resistance to BPA, features that are not of interest for toxicity markers. T. chuii presented an adequate sensitivity to BPA, compatible with parameters used in human toxicology for this substance, and is indicated as a potential biomarker for the presence of BPA in marine environments. The IC50 of T. chuii was 2.5 µM with R2 = 0.9, indicating reliability to demonstrate that low concentrations of BPA has significant toxicity to this species.