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Author Spotlight: Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: May 26, 2023
Physiology of Ca(2+) signalling in stem cells of different origins and differentiation stages
Oksana Forostyak1, Serhiy Forostyak1, Stepan Kortus2
1Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, Prague 14220, Czech Republic; Department of Neuroscience, Charles University, Second Faculty of Medicine, V Uvalu 84, 15006 Prague, Czech Republic.
Abstract:
Stem cells (SCs) of different origins have brought hope as potential tools for the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis. Calcium signalling plays a key role in SC differentiation and proliferation, and dysregulation of Ca(2+) homeostasis may instigate pathological scenarios. Currently, the role of ion channels and receptors in SCs is not fully understood. In the recent years, we found that (i) the pre-differentiation of human embryonic SCs (hESCs) led to the activation of Ca(2+) signalling cascades and enhanced the functional activities of these cells, (ii) the Ca(2+) homeostasis and the physiological properties of hESC-derived neural precursors (NPs) changed during long term propagation in vitro, (iii) differentiation of NPs derived from human induced pluripotent SCs affects the expression of ion channels and receptors, (iv) these neuronal precursors exhibited spontaneous activity, indicating that their electrophysiological and Ca(2+) handling properties are similar to those of mature neurones, and (v) in mesenchymal SCs isolated from the adipose tissue and bone marrow of rats the expression profile of ion channels and receptors depends not only on the differentiation conditions but also on the source from which the cells were isolated, indicating that the fate and functional properties of the differentiated cells are driven by intrinsic mechanisms. Together, identification and assignment of a unique ion channel and a Ca(2+) handling footprint for each cell type would be necessary to qualify them as physiologically suitable for medical research, drug screening, and cell therapy.
Insights
Calcium signaling is crucial for stem cell (SC) function in neurodegenerative disease treatments. Understanding ion channels and Ca(2+) handling is vital for qualifying SCs for medical applications.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Calcium Signaling
Background:
- Stem cells (SCs) offer potential for treating neurodegenerative diseases.
- Calcium (Ca2+) signaling is integral to SC differentiation and proliferation.
- Dysregulated Ca2+ homeostasis can contribute to disease pathology.
Purpose of the Study:
- To investigate the role of ion channels and Ca2+ signaling in various stem cell types.
- To understand how SC properties change during differentiation and propagation.
- To identify unique cellular fingerprints for SCs in medical applications.
Main Methods:
- Studied human embryonic stem cells (hESCs) and their neural precursors (NPs).
- Analyzed differentiation of human induced pluripotent stem cell-derived NPs.
- Examined ion channel and Ca2+ handling in rat mesenchymal stem cells (MSCs).
Main Results:
- Pre-differentiation of hESCs activated Ca2+ signaling and enhanced cell activity.
- Ca2+ homeostasis and properties of hESC-derived NPs changed with long-term culture.
- Differentiation of iPSC-derived NPs altered ion channel and receptor expression.
- Neuronal precursors showed spontaneous activity, mimicking mature neurons.
- MSC ion channel expression varied with differentiation and cell source, indicating intrinsic control.
Conclusions:
- SC differentiation and propagation significantly impact Ca2+ signaling and electrophysiological properties.
- Intrinsic mechanisms influence the functional characteristics of differentiated cells.
- Defining unique ion channel and Ca2+ handling profiles is essential for qualifying SCs for research and therapy.
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