Abstract

Human mesenchymal stem cells (hMSC) are becoming increasingly popular in tissue engineering. They are the most frequently used stem cell source for clinical applications due to their high potential to differentiate into several lineages. Cartilage is known for its low capacity for self-maintenance and currently there are no efficient methods to improve cartilage repair. Chondrogenic differentiation of hMSC isolated from different tissues is widely employed due to a high clinical demand for the improvement of cartilage regeneration. Calcium channels that are regulated by physical stimuli seem to play a pivotal role in chondrogenic differentiation of MSCs. These channels increase intracellular calcium concentration, which leads to the initiation of the relevant cellular processes that are required for differentiation. This review will focus on the impact of different physical stimuli, including electrical, electromagnetic/magnetic and mechanical on various calcium channels and calcium signaling mechanisms during chondrogenic differentiation of hMSC.

Highlights

  • The poor regenerative capacity of human articular cartilage is a major challenge for researchers and clinicians that are working in the area of cartilage repair and it has gained particular attention during the past decades

  • This review presents an up-to-date overview of the role of physical stimuli on calcium channels in chondrogenic differentiation of mesenchymal stem cells (MSCs)

  • In order to understand the mechanism of action of Electrical stimulation (ES), electromagnetic fields (EMF), or magnetic field on either cell type and mechanotransductive Ca2+ channels, and, their potential in developing novel therapies based on cell chondrogenic differentiation capability, first of all the parameters, such as frequency, intensity, and time of exposure have to be optimized for either living system where the experimental and environmental conditions are clearly analyzed, thereby allowing for the optimization of a treatment that may have beneficial regenerative effects

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Summary

Introduction

The poor regenerative capacity of human articular cartilage is a major challenge for researchers and clinicians that are working in the area of cartilage repair and it has gained particular attention during the past decades. MSCs can be isolated from different sources, including bone marrow, adipose tissue, synovial membrane, umbilical cord, dental pulp, menstrual blood, and others They are plastic- adherent cells characterized by expression of typical surface markers CD73, CD90, CD105 and lack of expression of hematogenic surface markers CD14, CD34, and CD45 and they have a potential to differentiate at least into chondrogenic, osteogenic and adipogenic lineages when cells are cultured under defined conditions in vitro. Members of the TRP channel superfamily were shown to be involved in chondrogenesis induction through activation of the SOX9 pathway [10] Stimulation of these calcium channels opens a new research area, which may lead to the development of innovative approaches to improve chondrogenic differentiation in vitro, and, most importantly, cartilage repair in vivo. We have focused on three different types of physical stimuli that have been described to influence calcium channel activation—electric, electromagnetic/magnetic, and mechanical forces

Calcium Signaling in Cells
VOCCs and Their Regulation
Calcium Oscillations during Chondrogenic Differentiation of MSCs
Stimulation of Chondrogenic Differentiation with Electric Fields
Stimulation of Chondrogenic Differentiation by Mechanical Forces
10. Conclusions
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