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An- other macrophage-based cell therapy, which is under clinical investigation for the treatment of congestive heart failure and critical limb ischemia, is Ixmyelocel-T, a mixture of autologous macrophages and mesenchymal stem cells (MSCs) derived from a patient's bone mar- row mononuclear cells and expanded in culture over 14 days [52-54].
By contrast, intramyocardial delivery of non-expanded autologous bone marrow mononuclear cells failed to show clinical improvement in a separate study of patients treated for ischemic cardiomyopathy [56], although the two treatments have not been directly compared in the same study.
For example, when tissue- engineered vascular grafts formed from human bone mononuclear cells and poly(glycolic acid) scaffolds were implanted into immuno- compromised mice, murine macrophages replaced the human cells within the grafts, later repopulating them with murine endothelial cells and smooth muscle cells and transforming them into patent, func- tional blood vessels over 24 weeks [93].
, Effect of transendocardial delivery of autologous bone marrow mononuclear cells on func- tional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial, JAMA 307 (16) (2012) 1717-1726.
, interleukins; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MCP-1/5, monocyte chemoattractant protein-1/5 (CCL2/CCL12); MHCII, major histocompatibility complex class II; MIP- 1α/β, macrophage inflammatory protein-1 alpha/beta (CCL3/CCL4); MNCs, mononuclear cells; MMPs, matrix metalloproteinases; MSCs, mesenchymal stromal cells; NF-κβ, nuclear factor kappa beta; PAMPs, pathogen-associated molecular patterns; PDGF, platelet-derived growth factor; PGE-2, prostaglandin E-2; ROS, reactive oxygen species; TAMs, tumor-associated macrophages; TGF- β1, transforming growth factor beta 1; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor.
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