Abstract
Introduction: Adipose-derived stem/stromal cells (ASCs) are considered a promising cell source for therapeutic angiogenesis because the cells can be prepared following a minimally invasive procedure and because they secrete a variety of angiogenic cytokines. In the present study, the influence of donor age and passage number on angiogenic activity of ASC-conditioned media (ASC-CM) was examined. Methods: Human ASCs (donor age, 5 months to 82 years; n = 10) were cultured, and ASC-CM were collected at passages 2, 4, and 6. The angiogenic activity of ASC-CM was evaluated with the tube formation assay using a system in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were co-cultured. The concentrations of vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF) in each ASC-CM were measured using an enzyme-linked immunosorbent assay. Results: A donor age over 60 years affected the proliferative capacity of ASCs at passage 4 and later. ASCCM significantly enhanced HUVEC tube formation, and this response was not influenced by donor age. ASC-CM at passage 6 showed a lower tube formation capacity compared to ASC-CM at passage 4, although the capacity was still equivalent to the positive control (medium containing10 ng/mL VEGF-A). A donor age over 26 years affected VEGF-A but not HGF levels in ASC-CM, although we found no direct correlation between VEGF-A/HGF levels and the tube formation capacity. Conclusion: Our results demonstrate a passage number-dependent but a donor age-independent decline in the angiogenic activity of ASC-CM.
Highlights
Adipose-derived stem/stromal cells (ASCs) are considered a promising cell source for therapeutic angiogenesis because the cells can be prepared following a minimally invasive procedure and because they secrete a variety of angiogenic cytokines
Cultured ASCs satisfy the minimal criteria for defining mesenchymal stem cells (MSCs) as proposed by the International Society of Cell Therapy based on their phenotype (CD73+, CD90+, CD105+, CD11b/CD14−, CD19/CD73b−, CD34−, CD45−, HLA-DR−), their plastic-adherent properties, and their potential to differentiate into multiple lineages including adipogenic, chondrogenic, and osteogenic lineages [2]
Correlation analysis revealed that neither the vascular endothelial growth factor-A (VEGF-A) nor the hepatocyte growth factor (HGF) level correlated with the tube formation capacity in ASC-conditioned media (ASC-CM). These results suggest that donor age affects VEGF-A secretion but not HGF secretion in ASCs, and that no significant relationship exists between levels of these angiogenic factors and the tube formation capacity
Summary
Adipose-derived stem/stromal cells (ASCs) are considered a promising cell source for therapeutic angiogenesis because the cells can be prepared following a minimally invasive procedure and because they secrete a variety of angiogenic cytokines. The phenotype and functional properties of ASCs are similar to bone marrow mesenchymal stem cells (MSCs). Cultured ASCs satisfy the minimal criteria for defining MSCs as proposed by the International Society of Cell Therapy based on their phenotype (CD73+, CD90+, CD105+, CD11b/CD14−, CD19/CD73b−, CD34−, CD45−, HLA-DR−), their plastic-adherent properties, and their potential to differentiate into multiple lineages including adipogenic, chondrogenic, and osteogenic lineages [2]. Because adipose tissue is abundant in most individuals and can be harvested with a less invasive procedure that required for harvesting bone marrow, ASCs are thought to be a promising cell source for a variety of cell-based therapies and tissue engineering [3]. Transplantation of ASCs improves recovery of blood flow in mice and rats following an ischemic vascular injury [4,5,6,7]
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