Abstract
Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.
Highlights
Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to selfrenew and to differentiate towards osteoblasts, chondrocytes, and adipocytes [1]
A recent review from Hassan et al extensively analyzed the different in vitro expansion protocols for MSCs isolated from different sources: the authors reported that expansion up to 20-fold can be achieved for adipose-derived MSCs (ADMSCs) and bone marrow MSCs (BM-MSCs) without compromising cell viability and differentiation potential, with bioreactor and multi-layered flask being the most effective bioprocessing strategies [4]
The newly discovered ability of Pulsed electromagnetic fields (PEMFs) to modulate miRNAs involved in osteogenesis deserves further investigation to unravel their potential for translation into therapeutical approaches [68]
Summary
Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to selfrenew and to differentiate towards osteoblasts, chondrocytes, and adipocytes [1] Due to their multilineage differentiation potential, MSCs represent an attractive cell source for regenerative medicine approaches. Cartilage engineering repair strategies relying on differentiation of MSCs represent an attractive candidate to treat cartilage lesions. In addition to their multilineage differentiation potential, MSCs have the ability to migrate to injured sites in response to environmental signals and promote tissue regeneration by either directly replacing damaged tissue or interacting with resident cells to promote endogenous repair. Treatments capable of improving the performance of MSCs, acting both on their repair/regenerative capacity and their ability to modulate the immune/inflammatory response, will bring significant value to current regenerative medicine and tissue repair approaches
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