There have been many studies showing that electrical stimulation can promote the maturation of hPSC-CMs, but few have explained the specific mechanism. So does anyone speculate what the possible mechanism is?
Dear Dr. Ning Hm
The heart is an electromechanical pump with CMs that are constantly exposed to regular electrical stimuli during the early development and into adulthood. In the development of the heart, the embryonic environment which includes the electrical field in addition to extracellular matrix, mechanical signals, and soluble factors, determine the cardiac lineage commitment. The external electrical stimulation can mimic the electric properties of native heart tissue and facilitate CM differentiation of hiPSCs, and continuous electrical stimulation preconditioning can facilitate the functional maturation of derived CMs.
The mechanism during electrical stimulation will include mediating the expression of the key cardiac transcription factors and structural genes through the activation of calcium signaling pathways as well as cooperation with PKC/ERK pathway networks.
For instance, the cardiac progenitor genes like the Nkx2-5 and GATA4 and the structural genes namely, alpha myosin heavy chain [αMHC] and connexin 43 [CX43] are upregulated by electrical stimulation in hiPSCs after 1-week of induction, while the relative expression of pluripotent markers namely, KLF4 and OCT4 are decreased.
Also, cardiogenic markers such as Nkx2-5, GATA4, and cardiac troponin T [cTnT] and peptides [such as Apelin] are significantly increased in differentiated hiPSCs under electrical stimulation.
Additionally, the mRNA levels of cardiac genes like the TNNI3, α-actinin, and ryanodine receptor 2 [RYR2] which is related to functional maturation are also upregulated by electrical stimulation.
Regards,
Malcolm Nobre
Electrical stimulation plays a pivotal role in promoting the maturation of cardiomyocytes, the specialized heart muscle cells. By mimicking the natural electrical environment of the heart, this technique can significantly enhance the development and function of these cells.
Key Mechanisms of Electrical Stimulation:
Electrical stimulation improve cardiomyocytes maturation in number of way by improving gene expression, calcium handling , increasing sarcomere organisation, and shortening, improving response to pacing and enhancing cellular alignment
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