Mesenchymal stem cells reside under precise hypoxic conditions that are paramount in determining cell fate and behavior (metabolism, proliferation, differentiation, etc.). In this work, we show that different oxygen tensions promote a distinct proliferative response and affect the biosynthetic demand and global metabolic profile of umbilical cord-mesenchymal stem cells (UC-MSCs). Using both gas-based strategies and CoCl2 as a substitute for the costly hypoxic chambers, we found that specific oxygen tensions influence the fate of UC-MSCs differently. While 5% O2 potentiates proliferation, stimulates biosynthetic pathways, and promotes a global hypermetabolic profile, exposure to <1% O2 contributes to a quiescent-like cell state that relies heavily on anaerobic glycolysis. We show that using CoCl2 as a hypoxia substitute of moderate hypoxia has distinct metabolic effects, when compared with gas-based strategies. The present study also highlights that, while severe hypoxia regulates global translation via mTORC1 modulation, its effects on survival-related mechanisms are mainly modulated through mTORC2. Therefore, the experimental conditions used in this study establish a robust and reliable hypoxia model for UC-MSCs, providing relevant insights into how stem cells are influenced by their physiological environment, and how different strategies of modulating hypoxia may influence experimental outcomes.
The main purpose of this paper is to show that if three specific contextual factors are present in a company, it is possible to achieve great performance improvements with a lean and industry 4.0 implementation. In terms of research methods, a case study was carried out of a project to implement digitalization and Lean practices in a cutlery company, which in fact encompassed a project of master’s degree in engineering and industrial management. Thus, the research question is: “It is possible to achieve major improvements in a lean and industry 4.0 implementation if three specific contextual factors are present in the company, namely (i) commitment of top management, (ii) knowledge on digitalization and lean, and (iii) very low Value-Added Ratio?”. Regarding the company project, action-research was adopted, and the project team began by mapping and diagnosing the production processes of the two product families (knives and spoons/forks). High levels of work in process, long throughput times, poor flow planning and control, and high stocks of finished products, quickly stood out in both families. Improvement proposals were developed and implemented, namely: (i) creation of a production scheduling and control system, (ii) improvement of the warehouse stock management system, and (iii) adoption of new routines, management tools, visual management, and kaizen meetings. The results achieved were excellent (e.g., throughput time reduced by 27.6% and productivity increased by 36.5%) and aligned with Sustainable Development Goals SDG 9 and 12. The findings of this study corroborate that exceptional results in the company performance can be achieved through a lean and industry 4.0 intervention, if the three referred contextual factors occur.
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