Inverse opal substrate-loaded mesenchymal stem cells contribute to decreased myocardial remodeling after transplantation into acute myocardial infarction mice

Abstract

BackgroundThe two-dimensional incubation method is now the most commonly method for mesenchymal stem cell (MSC) production. however, gene expression and secretion of growth factors are relatively low; thus, the transplanted cells cannot be effectively utilized for potential clinical applications after acute myocardial infarction (AMI).ObjectivesWe aimed to investigate whether our newly made substrates of inverse opal with specific surface microstructures for MSC culturing can increase the viability of the cells and can contributes to decreased myocardial remodeling after transplanted to AMI mice.MethodsThe inverse opal structure is fabricated by the convenient bottom-up approach of the self-assembly of colloidal nanoparticles. Mouse-derived MSCs were then cultured on the substrates when expanded at different times to investigate the cell growth status including morphology. Then the inverse opal substrates loaded MSCs were transplanted to AMI mice, cardiomyocyte apoptosis and LV remodeling were further compared. To explore the possible mechanisms of curation, the secretions and viability of MSCs on substrates were determined using mice ELISA kits and JC-1 mitochondrial membrane potential assay kits respectively at normal and hypoxic conditions.Results6 times expanded inverse opals allowed greatly the orderly growth of MSCs as compared to four (34% ± 10.6%) and two (20%±7.2%) times expanded as well as unexpanded (13%±4.1%) (P<0.001). Nearly 90% of MSCs showed orientation angle intervals of less than 30° when at the 6X expanded (89.6%±25%) compared to the percent of cells with 30°–60° (8.7%±2.6%) or ≥60° (1.7%±1.0%) orientation angle (P<0.001). After inverse opal loaded MSCs transplanted to AMI mice, greatly decreased apoptosis of cardiomyocytes (20.45%±8.64% vs.39.63%±11.71%, P<0.001) and infarction area (5.87±2.18 mm2 vs 9.31±3.11 mm2, P<0.001) were identified. In the end, the viability of inverse opal loaded MSCs determined by membrane potential (P<0.001) and the secretion of growth factors including VEGF-α, SDF-1 and Ang-1 (P<0.001) were both confirmed significantly higher than that of the conventional culture in petri dish.ConclusionThe structure of inverse opal can not only adjust the arrangement of MSCs but also contribute to its orientated growth. Inverse opal loaded MSCs transplantation extremely curbed myocardial remodeling, the underlying mechanisms might be the high viability and extremely higher secretions of growth factors of MSCs as devoted by this method.

Guarana (Paullinia cupana) as a potential tool for mesenchymal stromal cells priming in regenerative medicine

“…Their transmembrane potential is eventually lost after significant cellular damage ( 27 ). Lu et al ( 28 ) has observed improvements in mitochondrial membrane potential in activated MSCs and this was associated with better therapeutic effects. We demonstrated that guarana, as well as caffeine, preserved mitochondrial membrane potential and that caffeine promoted a significant hyperpolarization.…”

Advanced Nanomedicine Approaches for Myocardial Infarction Treatment

“… ECM/silk proteins NPs [ 125 ] ADSCs with inverse opals n.a. Inverse opals [ 126 ] ADSCs with simvastatin NPs Simvastatin Polymer NPs [ 127 ] SPIO-ADSCs n.a. Superparamagnetic iron oxide NPs [ 128 ] IONP–MSC–derived NVs Extracellular nanovesicles n.a.…”

“…Furthermore, Au@Pt/Alg hydrogel loaded with BASCs showed effective antioxidant and anti-inflammatory ability, enhanced the survival of implanted BASCs, and improved electrical conduction velocity and cardiac function, indicating the excellent ability of the hydrogel to promote cardiac repair. 14 In addition, melatonin-loaded PLGA‐mPEG nanoparticles, 124 chitosan-silk fibroin hydrogel incorporated with gold nanoparticles, 139 nanoparticles incorporated with ECM/silk proteins, 125 and inverse opals 126 were used to achieve higher ADSC survival rates in the infarcted areas and improve the therapeutic efficacy for MI treatment. In addition, ADSCs could also function as drug-delivery tools.…”

MSCs Contribute to the Conversion of Ly6Chigh Monocytes into Ly6Clow Subsets under AMI

“…(from C57BL/6 wild-type mice) were prepared as previously described [14]. The femurs and tibias of 6-week-old mice were first flushed with PBS (HyClone) to collect the bone marrow cells.…”