title: Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells.
abstract: Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.
authors: Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors: Jun Hee
authors: JH
authors: Lee
authors: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.|Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.
authors: Yong-Seok
authors: YS
authors: Han
authors: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.|Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.
authors: Sang Hun
authors: SH
authors: Lee
keywords: Adipose-derived mesenchymal stem cells; Apoptosis; Cell transplantation; Extracellular matrix; Ischemic disease; Spheroid