scholarly journals Intracellular label-free detection of mesenchymal stem cell metabolism within a perivascular niche-on-a-chip

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Simone Perottoni ◽  
Nuno G. B. Neto ◽  
Cesare Di Nitto ◽  
Ruslan I. Dmitriev ◽  
Manuela Teresa Raimondi ◽  
...  

The stem cell niche at the perivascular space plays a role in dictating the fate of stem cells within it. This study predicts in silico and models the perivascular space, in a miniaturised bioreactor, with non-invasive assessment of cell metabolism.

2020 ◽  
Author(s):  
Simone Perottoni ◽  
Nuno G. B. Neto ◽  
Cesare Di Nitto ◽  
Manuela Teresa Raimondi ◽  
Michael G. Monaghan

AbstractThe stem cell niche at the perivascular space in human tissue plays a pivotal role in dictating the overall fate of stem cells within it. Mesenchymal stem cells (MSCs), in particular, experience influential microenvironmental conditions, which induce specific metabolic profiles that affect processes such as cell differentiation and dysregulation of the immunomodulatory funtion. Reports focusing specifically on the metabolic status of MSCs under the effect of pathophysiological stimuli - in terms of flow velocities, shear stresses or oxygen tension – do not model heterogenous gradients, highlighting the need of more advanced models reproducing the metabolic niche. Organ-on-a-chip technology offers the most advanced tools for stem cell niche modelling thus allowing for controlled dynamic culture conditions while profiling tunable oxygen tension gradients. However, current systems for live cell detection of metabolic activity inside microfluidic devices require the integration of microsensors that allow for extracellular measurments only, giving innacurate and indirect information about the metabolic state of cells. Here, we present a metabolic toolbox coupling a miniatuirzed in vitro system for human-MSCs dynamic culture, that mimics microenvironmental conditions of the perivascular niche, with high-resolution imaging of intracellular metabolism. Using Fluorescence Lifetime Imaging Microscopy (FLIM) we monitor the spatial metabolic machinery and correlate it with experimentally validated intracellular oxygen concentration after designing the oxygen tension decay along the fluidic chamber by in silico models prediction. Our platform allows for the subjection of a metabolic profile to MSCs, mimicking the physiological niche in space and time, and its real-time monitoring representing a functional tool for modelling perivascular niches, relevant diseases and metabolic-related uptake of pharmaceuticals.


2019 ◽  
Vol 401 (1) ◽  
pp. 81-95 ◽  
Author(s):  
Dieter Häussinger ◽  
Claus Kordes

Abstract Recent evidence indicates that the plasticity of preexisting hepatocytes and bile duct cells is responsible for the appearance of intermediate progenitor cells capable of restoring liver mass after injury without the need of a stem cell compartment. However, mesenchymal stem cells (MSCs) exist in all organs and are associated with blood vessels which represent their perivascular stem cell niche. MSCs are multipotent and can differentiate into several cell types and are known to support regenerative processes by the release of immunomodulatory and trophic factors. In the liver, the space of Disse constitutes a stem cell niche that harbors stellate cells as liver resident MSCs. This perivascular niche is created by extracellular matrix proteins, sinusoidal endothelial cells, liver parenchymal cells and sympathetic nerve endings and establishes a microenvironment that is suitable to maintain stellate cells and to control their fate. The stem cell niche integrity is important for the behavior of stellate cells in the normal, regenerative, aged and diseased liver. The niche character of the space of Disse may further explain why the liver can become an organ of extra-medullar hematopoiesis and why this organ is frequently prone to tumor metastasis.


2020 ◽  
Vol 71 (2) ◽  
pp. 211-213
Author(s):  
K. Sato ◽  
S. Chitose ◽  
K. Sato ◽  
F. Sato ◽  
T. Kurita ◽  
...  

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