Amniotic mesenchymal stem cells have robust angiogenic properties and are effective in treating hindlimb ischaemia

• Published in: Cardiovascular research Vol. 93; no. 3; pp. 525 - 534
• Main Authors: Kim, Sung-Whan, Zhang, Hong-Zhe, Kim, Chae Eun, An, Hyun Sook, Kim, Jong-Min, Kim, Moo Hyun
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2012
• Subjects: Amnion - cytology; Animals; Cell Differentiation - physiology; Dermis - cytology; Disease Models, Animal; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Fibroblasts - cytology; Gene Expression Profiling; Graft Survival - physiology; Hindlimb - blood supply; Human Umbilical Vein Endothelial Cells; Humans; Ischemia - physiopathology; Ischemia - therapy; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Mesenchymal Stromal Cells - secretion; Mice; Mice, Inbred NOD; Mice, SCID; Neovascularization, Physiologic - physiology; Ischaemic hindlimb; Amnion; Angiogenesis; Cell-based therapy; Mesenchymal stem cells
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvr328

Aims In this study, we aimed to evaluate whether human amniotic mesenchymal stem cells (AMMs) have angio-vasculogenic properties and to determine their therapeutic effects on experimental ischaemia. Although AMMs are a promising source of stem cells, their angio-vasculogenic properties are not fully understood. Methods and results We have characterized AMMs by quantitative real-time polymerase chain reaction, Matrigel tube formation assays, and various in vitro endothelial differentiation assays. AMMs expressed significantly higher levels of representative proangiogenic genes, vascular endothelial growth factor-A, angiopoietin-1, hepatocyte growth factor, and fibroblast growth factor-2 (FGF-2) than adipose-derived mesenchymal stem cells. In addition, the anti-apoptotic factor Akt-1 was highly expressed in the AMMs. Cells were directly transplanted into the ischaemic hindlimbs of mice to evaluate their angio-vasculogenic and therapeutic effects. They spontaneously differentiate into vascular-like structures and exhibit endothelial-specific genes and proteins. In an in vivo study on hindlimb ischaemia, implantation of AMMS augmented blood perfusion and capillary density, indicating AMM-augmented neovascularization. The engraftment rate of AMMs was high, and the transplanted AMMs showed vasulogenic potential. Conclusion AMMs are not only markedly angiogenic but also vasculogenic, thus ameliorating hindlimb ischaemia. Our data suggest that AMMs have considerable therapeutic effects on ischaemic hindlimb through high angiogenic and engraftment abilities.