Open Access3D spheroid culture enhances survival and therapeutic capacities of MSC s injected into ischemic kidney
Author(s) -
Xu Yong,
Shi Taoping,
Xu Axiang,
Zhang Lei
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12651
Subject(s) - paracrine signalling , mesenchymal stem cell , hepatocyte growth factor , growth factor , cancer research , microbiology and biotechnology , basic fibroblast growth factor , fibronectin , apoptosis , extracellular matrix , biology , biochemistry , receptor
Three‐dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells ( MSC s). In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose‐derived MSC s for acute kidney injury ( AKI ). In vitro studies indicated that 3D spheroids of MSC s 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 MSC s, 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 MSC s 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 MSC s, and might be promising for AKI treatment.