Effect of electric stimulation on human chondrocytes and mesenchymal stem cells under normoxia and hypoxia

Abstract

During joint movement and mechanical loading, electric potentials occur within cartilage tissue guiding cell development and regeneration. Exposure of cartilage exogenous electric stimulation (ES) may imitate these endogenous electric fields and promote healing processes. Therefore, the present study investigated the influence of electric fields on human chondrocytes, mesenchymal stem cells and the co-culture of the two. Human chondrocytes isolated from articular cartilage obtained post-mortally and human mesenchymal stem cells derived from bone marrow (BM-MSCs) were seeded onto a collagen-based scaffold separately or as co-culture. Following incubation with the growth factors over 3 days, ES was performed using titanium electrodes applying an alternating electric field (700 mV, 1 kHz). Cells were exposed to an electric field over 7 days under either hypoxic or normoxic culture conditions. Following this, metabolic activity was investigated and synthesis rates of extracellular matrix proteins were analyzed. ES did not influence metabolic activity of chondrocytes or BM-MSCs. Gene expression analyses demonstrated that ES increased the expression of collagen type II mRNA and aggrecan mRNA in human chondrocytes under hypoxic culture conditions. Likewise, collagen type II synthesis was significantly increased following exposure to electric fields under hypoxia. BM-MSCs and the co-culture of chondrocytes and BM-MSCs revealed a similar though weaker response regarding the expression of cartilage matrix proteins. The electrode setup may be a valuable tool to investigate the influence of ES on human chondrocytes and BM-MSCs contributing to fundamental knowledge including future applications of ES in cartilage repair.

The effect of electric fields on hyaline cartilage: an in vitro and in silico study

“…A decrease in cell proliferation was observed after 2 and 7 days of stimulation, while an increase cell population was evidenced after 14 days of stimulation compared with controls. This finding contrasts with previous reports, which have not noticed that MSCs cultured in micromass and collagen scaffolds do not proliferate after 7 days of electrical stimulation [341], [343], [354]. However, it has been evidenced that short exposure times of electrical stimulation increased the proliferation rate of MSCs growth in monolayer in presence of chondrogenic medium [340].…”

“…Some literature reports have evidenced that micro-mass cultures of MSCs stimulated with 20 mV/cm at 1 and 60 kHz experienced an increase in SOX-9, aggrecan and collagen type II; however, the increase in gene expression was obtained under chondrogenic conditions using TGF-β3 [341], [343]. A recent study showed that MSCs encapsulated in bovine collagen-based scaffolds and stimulated with direct coupled EFs for seven days had weaker response regarding the expression of cartilage matrix proteins [354]. These results suggest that the stimulated HA-GEL injectable hydrogel here presented is a very good alternative to induce chondrogenic differentiation not only in the absence of exogenous factors, but also in the presence of a biophysical stimulus.…”

Electro‐Stimulation, a Promising Therapeutic Treatment Modality for Tissue Repair: Emerging Roles of Sulfated Glycosaminoglycans as Electro‐Regulatory Mediators of Intrinsic Repair Processes

“…[ 128 ] Electro‐stimulation increases the expression of collagen type II mRNA and aggrecan mRNA in human chondrocytes and mesenchymal stem cells, further supporting a role in tissue repair. [ 129 ]…”

Emerging Gene-Editing Modalities for Osteoarthritis

“…Exogenous-cell-based therapy is gaining traction for the regeneration of articular cartilage over stimulation therapy such as electric stimulation of endogenous cartilage growth factors [ 97 ]. Exogenous cell therapy can be done through the delivery of chondrocytes (either autologous or allogeneic), mesenchymal stem cells (MSCs), or extracellular vesicles [ 98 ].…”

“…MSCs are used for regenerative medicine due to their ability to promote regeneration based on environmental signals at sites of injury. As inhibitors of the immune system and multilineage differentiators, MSCs are an important alternative cell source for articular cartilage repair and regeneration [ 97 ]. MSCs derived from the synovial membranes of joints have been shown to be more effective in terms of articular cartilage formation in in vitro studies when compared to MSCs from other tissues, joint and nonjoint [ 99 , 100 ].…”