Editors' ChoiceRegenerative Medicine

Protein Cocktail Nourishes New Vessels

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Science Translational Medicine  17 Mar 2010:
Vol. 2, Issue 23, pp. 23ec45
DOI: 10.1126/scitranslmed.3001047

Angiogenesis is critical in the regeneration of tissues and organs. These developing body parts need new blood vessels to ensure sufficient transport of nutrients, cytokines, and cells that would otherwise be diffusion-limited. Therapeutic blood-vessel formation initially involved either the delivery of chemical agents or cell therapy, but for the latter, cell death was a considerable problem. The transplantation of endothelial cells (ECs) has shown some promise in therapeutic vascularization; however, even when the cells are delivered with the cytokine vascular endothelial growth factor (VEGF) stable vasculature fails to form. This failure stems from the absence of host mural cells, which are needed to stabilize the nascent vessels. In a recent article in Biomaterials, Jay et al. use a mouse model to suggest a possible solution: the codelivery of ECs, VEGF, and monocyte chemotactic protein-1 (MCP-1), which recruits host mural cells to the walls of the forming vessels.

VEGF and MCP-1 were encapsulated in alginate microparticles, which were combined with ECs in a collagen/fibronectin gel. The VEGF–MCP-1 cocktail caused a burst of functional vessel formation. The microparticles are less efficient at encapsulating MCP-1 than VEGF, and this situation leads to a rapid, lower-dose delivery of the former, which encourages the recruitment of host smooth-muscle cells and prevents the accumulation of inflammation-causing M1-macrophages. The authors note that VEGF is already known to be an effective agent for therapeutic angionensis for cases of restricted blood supply, as shown in the enhanced survival of transplanted ECs in a hindlimb ischemia model. Thus, they propose that their dual delivery method could be adapted to create a combined angiogenic and arteriogenic therapy for the treatment of ischemic disease.

S. M. Jay et al., Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization. Biomaterials 31, 3054–3062 (2010). [Full Text]

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