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1 WHOLE LUNG Tissue Engineering Petersen et al. [“Tissue-Engineered Lungs for in Vivo Implantation”, 2010] decellularized murine lungs and then recellularized them with epithelial cells and micro-vascular lung endothelial cells isolated from neonatal rat lungs. Suppose to design a specific bioreactor to mimic certain features of the human adult lung environment, including vascular perfusion (red arrows), which delivers oxygenated and glucose - rich medium to the lungs, and cyclic inflation -deflation of the alveoli with a liquid medium, mimicking ventilation (green arrows). Bioreactor sketch Exemplification of lung structure at alveolar level Answer briefly to the questions in the table: What is the therapeutic product? What are the elements that identify the therapeutic product as a PTC? In what phase of the regulatory process for new PTCs can this PTC be localized? What are the standards that apply in this stage of the PTC process of development? What are the risks associated with this PTC (immunogenic, tumour, teratoma, infection, toxicity)? 2 Classify the cell sources potentially usable in human patients for this therapy. Cell source Cell type/s Advantages Criticalities Can be used? NB: conventional therapy: drugs administration 3 EXERCISE A Knowing that the vascular medium flow rate Qm is equal to 5 𝑙𝑙 𝑚𝑚𝑚𝑚𝑚𝑚, the arterial concentration c1 of glucose is 4.86 mM [P. Pezzati, M. Tronchin, G. Messeri. Biochimica clinica, 2004, vol. 28, n. 5-6] and the venous concentration c2 is 5% lower, assess the total consumption of glucose. Determine also the total consumption of oxygen knowing that the difference of oxygen concentration between arterial and venous blood is 2 mM. Consider that the alveolo-capillary oxygen transfer (𝑄𝑄𝑎𝑎) is 310 𝑚𝑚𝑙𝑙 𝑚𝑚𝑚𝑚𝑚𝑚 and the molar volume of…