3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney

Abstract

Three‐dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose‐derived MSCs for acute kidney injury (AKI). In vitro studies indicated that 3D spheroids of MSCs produced higher levels of extracellular matrix proteins (including collagen I, fibronectin and laminin), and exhibited stronger anti‐apoptotic and anti‐oxidative capacities than two‐dimensional (2D) cultured cells. Furthermore, 3D culture increased the paracrine secretion of cytokines by MSCs, including angiogenic factors (VEGF and basic fibroblast growth factor), anti‐apoptotic factors (epidermal growth factor and hepatocyte growth factor), the anti‐oxidative factor insulin‐like growth factor and the anti‐inflammatory protein tumour necrosis factor‐alpha stimulated gene/protein 6. Consistent with in vitro experiments, 3D spheroids of MSCs showed enhanced survival and paracrine effects in vivo. More importantly, when injected into the kidney of model rats with ischemia‐reperfusion (I/R)‐induced AKI, 3D spheroids were more beneficial in protecting the I/R kidney against apoptosis, reducing tissue damage, promoting vascularization and ameliorating renal function compared with 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs, and might be promising for AKI treatment.

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

“…3D-culture models can be divided into those utilizing scaffold materials and scaffold-free, cell-only systems. Scaffold free-systems, such as hanging drop spheroid formation, have been shown to better preserve regenerative capacity of mesenchymal stem cells compared to monolayer culture 26 . Embedding in scaffold materials such as PLGA has been shown to preserve tenocyte phenotype better than 2D culture 8 .…”

Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury

“…Using 3D spheroid culture, Xu et al found that 3D spheroids of MSCs produced higher levels of extracellular matrix (ECM) and had significantly higher expression of the ROS‐scavenging protein Bcl‐2 and prosurvival protein phosphorylated AKT when stimulated by an oxidative condition of H 2 O 2 . After injection into rat models of I/R‐induced AKI, these cells showed enhanced survival rate confirmed by DiI staining, as well as enhanced therapeutic effects of MSCs for AKI …”

“…Improved culture conditions were also beneficial for MSCs’ paracrine ability. 3D spheroid culture increased the secretion of VEGF, bFGF, epidermal growth factor (EGF), HGF, IGF and tumour necrosis factor‐alpha stimulated gene/protein 6 (TSG‐6) . In 2013, Katsuno et al cultured MSCs in a low serum culture medium containing (2% fetal bovine serum) (lMSCs).…”

“…3D spheroid culture increased the secretion of VEGF, bFGF, epidermal growth factor (EGF), HGF, IGF and tumour necrosis factor-alpha stimulated gene/protein 6 (TSG-6). 39…”

Autologous bionic tissue for inguinal hernia repair

“…In this research, we prepared an ABT based on PLGA scaffold and autologous bone marrow‐derived MSCs for the treatment of inguinal hernias in rabbit models. Current data showed that MSCs produced a variety of ECM complexes, such as collagen, elastin, HA or GAG, as well as functional proteins such as integrins, fibronectin (Xu, Shi, Xu, & Zhang, ). We found that MSCs reduced inflammation caused by PLGA scaffold by increasing Macrophage 2 (M2) infiltration or M2/M1 ratio (Chamberlain, Saether, Aktas, & Vanderby, ).…”