Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2021; 13(4): 260-280
Published online Apr 26, 2021. doi: 10.4252/wjsc.v13.i4.260
Calcium channels and their role in regenerative medicine
Nassem Ahamad, Brij B Singh
Nassem Ahamad, Brij B Singh, School of Dentistry, UT Health Science Center San Antonio, San Antonio, TX 78257, United States
Author contributions: Ahamad N and Singh BB wrote and edited this manuscript.
Supported by National Institute of Dental & Craniofacial Research, No. 1R21DE028265-01A1.
Conflict-of-interest statement: The authors have nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Brij B Singh, PhD, Dean, Full Professor, School of Dentistry, UT Health Science Center San Antonio, 7703, Floyd Curl Dr., San Antonio, TX 78257, United States.
Received: January 19, 2021
Peer-review started: January 19, 2021
First decision: February 13, 2021
Revised: February 22, 2021
Accepted: March 29, 2021
Article in press: March 29, 2021
Published online: April 26, 2021

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.