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 (Ca²⁺) promotes the proliferation of MSCs, and thus can assist in transplantation therapy. Ca²⁺ signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors, Ca²⁺ channels/pumps/exchangers, Ca²⁺ buffers, and Ca²⁺ 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.

Keywords: Ca²⁺ signaling; Ca²⁺ channels; Transient receptor potential channel 1/Orai1 stem cells; Regenerative medicine; Stem cells

Core Tip: Regenerative medicine has the potential to replace damaged tissues. Stem cells provide new hope for regenerative therapy as they have indefinite self-renewable capability and can differentiate into all cell types. Stem cells can be obtained from both exogenous and endogenous sources. Moreover, stem cells migrate towards the damaged organs; however, signaling molecules/factors that allow them to move to damaged organs and facilitate repair have not been fully identified. Ca²⁺ signaling is critical for appropriate functioning of stem cells. Importantly, Ca²⁺ signaling is highly adaptable, and how it modulates stem cell function and its regenerative capacity is discussed in this article.