1. Ex vivo generation of a highly potent population of circulating angiogenic cells using a collagen matrix
- Author
-
Kuraitis, Drew, Hou, Chenchen, Zhang, Yan, Vulesevic, Branka, Sofrenovic, Tanja, McKee, Daniel, Sharif, Zahra, Ruel, Marc, and Suuronen, Erik J.
- Subjects
- *
NEOVASCULARIZATION , *COLLAGEN , *CELL populations , *COLLOIDS in medicine , *CELL culture , *CELLULAR therapy , *BIOMEDICAL materials - Abstract
Abstract: Biomaterials that have the ability to augment angiogenesis are highly sought-after for applications in regenerative medicine, particularly for revascularization of ischemic and infarcted tissue. We evaluated the culture of human circulating angiogenic cells (CAC) on collagen type I-based matrices, and compared this to traditional selective-adhesion cultures on fibronectin. Culture on a collagen matrix supported the proliferation of CD133+ and CD34+CD133+ CACs. When subjected to serum starvation, the matrix conferred a resistance to cell death for CD34+ and CD133+ progenitors and increased phosphorylation of Akt. After 4days of culture, phenotypically enriched populations of endothelial cells (CD31+CD144+) and progenitor cells (CD34+CD133+) emerged. Culture on matrix upregulated the phosphorylation and activation of ERK1/2 pathway members, and matrix-cultured cells also had an enhanced functional capacity for adhesion and invasion. These functional improvements were abrogated when cultured in the presence of ERK inhibitors. The formation of vessel-like structures in an angiogenesis assay was augmented with matrix-cultured cells, which were also more likely to physically associate with such structures compared to CACs taken from culture on fibronectin. In vivo, treatment with matrix-cultured cells increased the size and density of arterioles, and was superior at restoring perfusion in a mouse model of hindlimb ischemia, compared to fibronectin-cultured cell treatment. This work suggests that a collagen-based matrix, as a novel substrate for CAC culture, possesses the ability to enrich endothelial and angiogenic populations and lead to clinically relevant functional enhancements. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF