ABSTRACT
We present a computational fluid dynamics (CFD)-based model aimed at the identification of optimized culture conditions promoting efficient cardiogenesis of hydrogel-bead-encapsulated embryonic stem cells (ESCs) within a rotating bioreactor. The numerical approach, integrating diffusion, convection, and multiphase fluid dynamics calculations, allowed to evaluate (i) the microgravity motion of the floating beads, (ii) the O(2) delivery to the cells, also (iii) taking into account the cellular O(2) consumption, as a function of different rotation speeds of the breeding chamber. According to our results, a 25 rpm rotation (i) enhances an adequate mixing of the cell carriers, avoiding sedimentation and excessive packing, also maintaining a quite homogeneous distribution of the suspended beads and (ii) imparts a proper cellular O(2) supply, providing cells close to a normoxia condition. The bioreactor working conditions derived from the numerical analysis allowed the attainment of in vitro long-term cell viability maintenance, supporting efficient large-scale generation of ESC-derived cardiomyocytes (ESC-DCs) through a chemical-based conditioning bioprocess. In conclusion, we demonstrated the feasibility of using CFD-based tools, as a reliable and cost-effective strategy to assist the design of a 3D cardiogenic bioprocess.
Subject(s)
Cell Culture Techniques/methods , Computer Simulation , Embryonic Stem Cells/cytology , Models, Biological , Organogenesis , Animals , Bioreactors , Cell Death , Cell Proliferation , Cell Survival , Cells, Immobilized/cytology , Cells, Immobilized/metabolism , Embryonic Stem Cells/metabolism , Gene Expression Regulation, Developmental , Kinetics , Mice , Myocytes, Cardiac/cytology , Organogenesis/genetics , Oxygen/metabolism , Partial Pressure , Reverse Transcriptase Polymerase Chain Reaction , Rotation , WeightlessnessABSTRACT
GOALS OF WORK: The goals of the study were to determine the relationship of upper gastrointestinal symptoms with nutritional status and to assess their association with performance status in patients with advanced cancer. MATERIALS AND METHODS: We studied 143 patients (50 F, 93 M, mean age 68 +/- 11 years, mean body mass index 22.39 +/- 4.3 kg/m(2)). Assessed symptoms were the following: anorexia, nausea, vomiting, dysphagia for solids, dysphagia for liquids, xerostomia, hypogeusia, dysgeusia, hiccup and chewing disturbances. We determined anthropometric parameters, daily energy intake and serum albumin, prealbumin and transferrin. MAIN RESULTS: The most common upper gastrointestinal symptoms were xerostomia (73%), anorexia (49%) and chewing disturbances (40%). Fifty-four percent of patients had weight loss greater than 10%. Seventy-three patients (51%) had daily energy intake lower than their resting energy expenditure. Mean serum prealbumin, albumin and transferrin were below normal range. Mean Eastern Cooperative Oncology Group performance status scale was 3.1 +/- 0.49. Symptoms were often strongly correlated, and usually, patients experienced at least three upper gastrointestinal symptoms at the same time. Anorexia, nausea and vomiting were the symptoms mostly correlated with other symptoms. A correlation was found between vomiting and hiccup. Energy intake (EI) was the nutritional parameter mostly affected by upper gastrointestinal symptoms; moreover, EI is the most predictive factor of upper gastrointestinal symptoms, particularly xerostomia, anorexia and dysphagia for solids. CONCLUSIONS: Upper gastrointestinal symptoms are linked to nutritional parameters: In particular, energy intake represents the most predictive variable of symptom occurrence. The performance status is not affected by upper gastrointestinal symptoms. A rigorous nutritional assessment and the managing of upper gastrointestinal symptoms are crucial in patients with advanced cancer.
