MusCle brOadband Impedance spectroscopy of ME/CFS patients for solving the roWdy diagnosis from liViNg CELLs
Progetto Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a
chronic disease characterized by unexplained and persistent postexertional
fatigue, that affects more than 2 million EU citizens. Although
many causes have been hypothesized, the aetiology and symptoms
heterogeneity of ME/CFS remains blurry, and no single biomarker or
pathognomonic sign has been identified yet. Skeletal muscle (SM) has been
mostly neglected in the diagnosis while persistent fatigue is strictly linked to
muscle metabolism and plasticity. SM plasticity resides in satellite cells
(SCs), adult stem cells that continuously renew muscle fibres. The lack of
SM recovery post exertion suggests altered functions of SCs. SCs, as well
as SM fibres, are ionically and metabolically regulated at the plasmamembrane,
cytosolic and mitochondria levels. Cultured SCs are an in vitro
model to investigate patients’ SM. Preliminary data on ME/CFS SCs showed
a significant increased [Ca2+] at the resting condition along with a high
oxidative stress exemplified mainly by elevated anion superoxide species.
These ionic species are crucial for the electrophysiology SCs and impact
the membrane and organelle integrity, both of which influence the cell
dielectric properties and electrical impedance.
MiCrOWaViNgCELL will characterize SCs by label-free, high-throughput
broadband electrical cytometry, which captures impedance signature of
single cells and reflects ionic, molecular, organelle and metabolic changes
on the subcellular and cellular levels to mirror the ME/CFS SM pathology.
The impedance signatures will be correlated with biological changes to
decipher and distinguish healthy versus ME/CFS SCs. The
MiCrOWaViNgCELL approach holds a great promise to objectively
diagnose ME/CFS patients. The proposed work will validate this approach
and aim to move it from the bench side to bedside, benefiting the ME/CFS
community.