Fig. 4. Lineage hierarchy of vascluogenic cells participating in postnatal angiogenesis.

Probable cellular origins of postnatal vasa vasorum angiogenesis in normal and pathological states include differentiation of adventitia-laden progenitor cells toward a pericyte phenotype, and subsequent migration toward PDGF-BB producing branching endothelial tip cells and/or differentiation toward SMCs. Tissue-resident ECFCs give rise to smooth muscle and mature endothelial cells. Pericytes can adopt a more mature SMC phenotype. Bone marrow–derived cells are precursors of myeloid angiogenic cells, macrophages, SMCs, pericytes, and endothelial cells. Endothelial cells can transdifferentiate toward smooth muscle and pericytes through endothelial-to-mesenchymal transition (EndoMT). Tissue-resident Sca1⁺ cells that are non–bone marrow–derived may originate from medial SMCs and give rise to mature SMCs, endothelial cells, and macrophages.