Magnetic Nanoparticles and Magnetic Field Exposure Enhances Chondrogenesis of Human Adipose Derived Mesenchymal Stem Cells But Not of Wharton Jelly Mesenchymal Stem Cells.

Luminita Labusca,Cristina Stavila,Anca Emanuela Minuti,Camelia Danceanu,Nicoleta Lupu,Horia Chiriac,Petru Plamadeala,Dumitru-Daniel Herea

doi:10.3389/fbioe.2021.737132

Abstract

Purpose: Iron oxide based magnetic nanoparticles (MNP) are versatile tools in biology and medicine. Adipose derived mesenchymal stem cells (ADSC) and Wharton Jelly mesenchymal stem cells (WJMSC) are currently tested in different strategies for regenerative regenerative medicine (RM) purposes. Their superiority compared to other mesenchymal stem cell consists in larger availability, and superior proliferative and differentiation potential. Magnetic field (MF) exposure of MNP-loaded ADSC has been proposed as a method to deliver mechanical stimulation for increasing conversion to musculoskeletal lineages. In this study, we investigated comparatively chondrogenic conversion of ADSC-MNP and WJMSC with or without MF exposure in order to identify the most appropriate cell source and differentiation protocol for future cartilage engineering strategies. Methods: Human primary ADSC and WJMSC from various donors were loaded with proprietary uncoated MNP. The in vitro effect on proliferation and cellular senescence (beta galactosidase assay) in long term culture was assessed. In vitro chondrogenic differentiation in pellet culture system, with or without MF exposure, was assessed using pellet histology (Safranin O staining) as well as quantitative evaluation of glycosaminoglycan (GAG) deposition per cell. Results: ADSC-MNP complexes displayed superior proliferative capability and decreased senescence after long term (28 days) culture in vitro compared to non-loaded ADSC and to WJMSC-MNP. Significant increase in chondrogenesis conversion in terms of GAG/cell ratio could be observed in ADSC-MNP. MF exposure increased glycosaminoglycan deposition in MNP-loaded ADSC, but not in WJMSC. Conclusion: ADSC-MNP display decreased cellular senescence and superior chondrogenic capability in vitro compared to non-loaded cells as well as to WJMSC-MNP. MF exposure further increases ADSC-MNP chondrogenesis in ADSC, but not in WJMSC. Loading ADSC with MNP can derive a successful procedure for obtaining improved chondrogenesis in ADSC. Further in vivo studies are needed to confirm the utility of ADSC-MNP complexes for cartilage engineering.

Highlights

Musculoskeletal diseases are an increasing burden worldwide and a principal cause of persistent pain and disability
ADSC are relatively easy to extract by means of enzymatic or mechanical methods from the adipose tissue derived from elective cosmetic procedures
We found that viability of Wharton jelly-derived mesenchymal stem cells (WJMSC) exposed to MNPs after 24 h was only 83,5% compared to non-loaded control as assessed by cell mitochondrial activity

Summary

Introduction

Musculoskeletal diseases are an increasing burden worldwide and a principal cause of persistent pain and disability. Mechanical stem cell preconditioning using biophysical stimulation by applying various types of mechanical stress within dynamic bioreactors (compression, shear stress, and hydrostatic pressure) requires ancillary equipment and often a direct contact with the cells or cell media This introduces supplementary steps in the process of cell manufacturing when intending clinical application. Iron oxide MNP internalized by ADSC preserve their proliferative and differentiation capability while inducing cell magnetization This is opening fascinating possibilities for remote cell manipulation under magnetic field (MF) aiming for MNP mediated cell actuation. Such particularity can be used as a modality to deliver remote micromechanical stimulation to stem cells differentiating to musculoskeletal lineages—osteoblasts and chondrocytes (Lima et al, 2015)

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