Kang, Jung-Mi Yoon, Jeong-Kee Oh, Seong-ja Kim, Byung-Soo Kim, Sang-Heon 2024-01-19T23:03:15Z 2024-01-19T23:03:15Z 2021-09-03 2018-04 1937-3341 https://pubs.kist.re.kr/handle/201004/121560 Peripheral artery disease (PAD) is an ischemic disease characterized by reduced blood flow to the legs, feet, and hands. Human mesenchymal stem cells are an attractive cell source to treat PAD in regenerative medicine. However, in clinical applications, the use of adult stem cells has several limitations, such as low cell viability and low therapeutic efficiency. In this study, we described an innovative method of culturing three-dimensional stem cell clusters (Angiocluster [AC]), demonstrated the potential for ACs to differentiate into vascular cells, and assessed the synergistic effects of ACs and angiopoietin-1 (Ang-1) on angiogenesis in ischemic animal models. ACs were formed by culturing human adipose-derived stem cells (hASCs) on a maltose-binding protein-linked basic fibroblast growth factor-immobilized polystyrene surface. ACs released various angiogenic factors, such as vascular endothelial growth factor and interleukin-8, and could differentiate into endothelial lineage cells. However, ACs did not secrete Ang-1, which is an essential component of vascular maturation and anti-inflammation. ACs were combined with Ang-1 and were transplanted into the ischemic lesions of mice for 28 days. Most of the mice receiving the AC+Ang-1 treatment exhibited limb salvage and exhibited similar blood perfusion ratio compared to normal limb. The combination therapy of AC and Ang-1 enhanced angiogenic efficacy by increasing blood vessel regeneration and facilitating the implantation of stem cells into host vessels. Importantly, fibrotic collagen was observed in most of the groups after 28 days of treatment, except for the AC+Ang-1 group. This indicates that the combination therapy is synergistic in minimizing ischemic fibrosis and muscle degeneration. Our results demonstrate that the combination therapy significantly enhanced tissue regeneration and angiogenic efficacy of hASCs and may have wide applications in regenerative medicine. English MARY ANN LIEBERT, INC ANGIOGENESIS DIFFERENTIATION ENHANCEMENT MAINTENANCE MECHANISMS SECRETION SUBSTRATE ADHESION DELIVERY Synergistic Therapeutic Effect of Three-Dimensional Stem Cell Clusters and Angiopoietin-1 on Promoting Vascular Regeneration in Ischemic Region Article 10.1089/ten.tea.2017.0260 1 TISSUE ENGINEERING PART A, v.24, no.7-8, pp.616 - 630 TISSUE ENGINEERING PART A 24 7-8 616 630 scie scopus 000429016300009 2-s2.0-85044864665 Cell & Tissue Engineering Cell Biology Engineering, Biomedical Materials Science, Biomaterials Cell Biology Engineering Materials Science Article ANGIOGENESIS DIFFERENTIATION ENHANCEMENT MAINTENANCE MECHANISMS SECRETION SUBSTRATE ADHESION DELIVERY human adipose-derived stem cells growth factor immobilization three-dimensional stem cell clusters angiopoietin-1 critical limb ischemia angiogenesis