Towards Regenerative Audiology: Immune Modulation of Adipose-Derived Mesenchymal Cells Preconditioned with Citric Acid-Coated Antioxidant-Functionalized Magnetic Nanoparticles

Abstract

Introduction and Background: Based on stem cells, bioactive molecules and supportive structures, regenerative medicine (RM) is promising for its potential impact on field of hearing loss by offering innovative solutions for hair cell rescue. Nanotechnology has recently been regarded as a powerful tool for accelerating the efficiency of RM therapeutic solutions. Adipose-derived mesenchymal cells (ADSCs) have already been tested in clinical trials for their regenerative and immunomodulatory potential in various medical fields; however, the advancement to bedside treatment has proven to be tedious. Innovative solutions are expected to circumvent regulatory and manufacturing issues related to living cell-based therapies. The objectives of the study were to test if human primary ADSCs preconditioned with magnetic nanoparticles coated with citric acid and functionalized with antioxidant protocatechuic acid (MNP-CA-PCA) retain their phenotypic features and if conditioned media elicit immune responses in vitro. MNP-CA-PCA was synthesized and characterized regarding size, colloidal stability as well as antioxidant release profile. Human primary ADSCs preconditioned with MNP-CA-PCA were tested for viability, surface marker expression and mesenchymal lineage differentiation potential. Conditioned media (CM) from ADSCs treated with MNP-CA-PCA were tested for Il-6 and IL-8 cytokine release using ELISA and inhibition of lectin-stimulated peripheral blood monocyte proliferation. Results: MNP-CA-PCA-preconditioned ADSCs display good viability and retain their specific mesenchymal stem cell phenotype. CM from ADSCs conditioned with MNP-CA-PCA do not display increased inflammatory cytokine release and do not induce proliferation of allergen-stimulated allogeneic peripheral blood monocytes in vitro. Conclusions: While further in vitro and in vivo tests are needed to validate these findings, the present results indicated that CM from ADSCs preconditioned with MNP-CA-PCA could be developed as possible cell-free therapies for rescuing auditory hair cells.

Elastomeric Polyesters in Cardiovascular Tissue Engineering and Organs-on-a-Chip

“…12 Another recent design has looked into modification of patterns and porosity to obtain desirable elasticity matching that of the cardiac tissue. 25 Due to its tunable mechanical properties, the ability to be micromolded to various 3D patterns, and degradation into immunomodulatory monomers (i.e., citric acid 103 and itaconate 104 ), PICO has a great potential for 108 and staples 109−111 were used in surgical applications for holding tissues together, stopping body fluids and enabling healing mechanisms. These methods not only require an expert surgeon to apply them, but they also promote chronic inflammation, 112 involve a risk of infection, 113 and are hard to apply depending on the mechanics of the tissue of interest.…”

“…Another recent design has looked into modification of patterns and porosity to obtain desirable elasticity matching that of the cardiac tissue . Due to its tunable mechanical properties, the ability to be micromolded to various 3D patterns, and degradation into immunomodulatory monomers (i.e., citric acid and itaconate), PICO has a great potential for application in scaffolds for various soft tissues and in vivo implantation. PICO degradation releases itaconate (ITA), which has demonstrated capacity as a small molecule to regulate inflammation but has been limited in efficacy through oral delivery due to rapid removal from circulation .…”