Physiology of Ca2+ signalling in stem cells of different origins and differentiation stages

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.

TRPC3‐mediated Ca2+ signals as a promising strategy to boost therapeutic angiogenesis in failing hearts: The role of autologous endothelial colony forming cells

“…Understanding the signal transduction pathways that determine EPC activity is indispensable to enhance their regenerative outcome (Moccia, Bonetti, et al, ; Moccia, Dragoni, et al, ; Moccia, Lodola, et al, ). Intracellular Ca 2+ signals lie at the center of an intricate network of signalling cascades that finely tune stem cell behavior (Forostyak et al, ; Hao, Webb, Miller, & Yue, ; Moccia, Ruffinatti, & Zuccolo, ; Moccia, Tanzi, & Munaron, ; Pinto et al, ). Manipulating the Ca 2+ response to growth factors and local developmental cues has been shown to redirect stem/progenitor cell fate towards the desired lineage (Kawano et al, ; Yang & Li, ) and/or to increase the rate of expansion both in vitro (Kong et al, ; Ferreira‐Martins et al, ) and in vivo (Ferreira‐Martins et al, ).…”

Mesenchymal Stem Cells: A Future Option for Intervening Disease Management

“…The flow of calcium from the extracellular matrix (ECM) through mechanosensitive (Figure 1). Adult differentiated cells exhibit varied calcium dynamics depending on their anatomical location, tissue origins and physiological functions [27]. Cells of cardiac and vascular tissues, for example, withstand more stress, and their Ca 2+ buffering ability is higher than other cells [28,29].…”

“…The threshold of the progenitor cells like MSCs makes it unique in understanding the Ca 2+ homeostasis, for example, human MSCs (hMSCs) exhibit spontaneous Ca 2+ oscillations, a phenomenon not routine in other matured cells and progenitors with a few exceptions [32] though like other cell types in MSCs Ca 2+ oscillations are triggered by influx of extracellular Ca 2+ and release from endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors by calciuminduced calcium release [27]. There are studies that suggest mesenchymal stem cells respond to the extracellular Ca 2+ levels sensed by calcium sensing receptor (CaSR) in the cell membrane for its proliferation and differentiation [33].…”

Functional properties of different collagen scaffolds to create a biomimetic niche for neurally committed human induced pluripotent stem cells (iPSC)

“…Under certain pathological conditions, in which the central nervous system (CNS) microenvironment is altered due to disease-induced stress, infections or trauma, clinically effective therapies are currently lacking [7]. Restoring the function of a damaged brain or spinal cord has always been a challenge due to their limited capacity for regeneration.…”