Calcium channels and their role in regenerative medicine

Abstract

Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types. Based on their plasticity potential, they are divided into totipotent (morula stage cells), pluripotent (embryonic stem cells), multipotent (hematopoietic stem cells, multipotent adult progenitor stem cells, and mesenchymal stem cells [MSCs]), and unipotent (progenitor cells that differentiate into a single lineage) cells. Though bone marrow is the primary source of multipotent stem cells in adults, other tissues such as adipose tissues, placenta, amniotic fluid, umbilical cord blood, periodontal ligament, and dental pulp also harbor stem cells that can be used for regenerative therapy. In addition, induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells, and thus could be another source for regenerative medicine. Several diseases including neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, virus infection (also coronavirus disease 2019) have limited success with conventional medicine, and stem cell transplantation is assumed to be the best therapy to treat these disorders. Importantly, MSCs, are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair. Moreover, MSCs have the potential to migrate towards the damaged area, which is regulated by various factors and signaling processes. Recent studies have shown that extracellular calcium (Ca 2+ ) promotes the proliferation of MSCs, and thus can assist in transplantation therapy. Ca 2+ signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors, Ca 2+ channels/pumps/exchangers, Ca 2+ buffers, and Ca 2+ sensors, which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity, which will be discussed in this review.

Calcium Signaling Regulates Autophagy and Apoptosis

“…The principal tissue reservoir of mammalian adult stem cells is the bone marrow. However, other sources are skin, placenta, adipose tissue and umbilical cord, where these stem cells, especially MSCs, proliferate and differentiate and heal the spoiled tissue during injury [91]. Self-renewal and differentiation requirements drive stem cells' capacity that is dependent on their ability to have adequate autophagic processes [92].…”

Increasing cytosolic Ca2+ levels restore cell proliferation and stem cell potency in aged MSCs

“…Mammalian bone marrow is recognized as the largest reservoir of adult stem cells and a variety of stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), multipotent adult progenitor cells (MAPCs), and even small embryonic-like stem cells (VSELs) ( Ahamad and Singh, 2021 ). Though bone marrow is the primary source of MSCs in adults, other tissues such as adipose tissues, placenta, amniotic fluid, umbilical cord blood, periodontal ligament, and dental pulp also harbor MSCs.…”

“…Though bone marrow is the primary source of MSCs in adults, other tissues such as adipose tissues, placenta, amniotic fluid, umbilical cord blood, periodontal ligament, and dental pulp also harbor MSCs. However, bone marrow still remains the most common and consistently trustworthy source for in vitro studies, including isolation, culture, propagation, and characterization ( Ahamad and Rath, 2019 ; Ahamad and Singh, 2021 ). In addition, recent research has revealed that stem cells do not remain static, and their properties, including surface marker expression and stem cell potential, are decreased as they are passaged and in aged animals.…”

Twist1 as a pivotal regulator of hematopoietic stem cell fate

“…In embryonic and human mesenchymal stem cells, calcium entry into the cytoplasm from the extracellular space is mediated mainly by store-operated Ca 2+ channels rather than the voltage-gated calcium channels (VGCCs) or by the Na + /Ca 2+ exchangers. 11 The mechanism of calcium entry seems to be different in HSCs. A previous study found that suppression of intracellular Ca 2+ level into HSCs by Nifedipine (blockers of L-type voltage-gated Ca 2+ channels) abolished the resultant mitochondrial activation and prolonged cell division interval in HSCs, and simultaneously achieved both cell division and HSC maintenance.…”

“…In embryonic and human mesenchymal stem cells, calcium entry into the cytoplasm from the extracellular space is mediated mainly by store-operated Ca 2+ channels rather than the voltage-gated calcium channels (VGCCs) or by the Na + /Ca 2+ exchangers 11 . The mechanism of calcium entry seems to be different in HSCs.…”