The role of progenitor cells in the development of intimal hyperplasia

Abstract

Recent evidence has suggested that bone marrow derived progenitor cells may contribute to the development of intimal hyperplasia after arterial injury, a process that classically has been believed to involve extracellular matrix deposition and the migration and proliferation of cells within the arterial wall. The first studies demonstrating the existence of bone marrow derived cells in the neointima employed mouse models of arterial injury in conjunction with whole bone marrow transplant. Later studies have shown specifically that bone marrow derived hematopoietic or mesenchymal stem cells can be recruited to the neointima and differentiate into smooth muscle cells or endothelial cells. Although the data vary widely depending on different animal models of arterial injury and methods of labeling bone marrow derived cells, it appears that progenitor cells do indeed contribute to intimal hyperplasia, at least in mouse models of arterial injury. To date, signaling molecules such as c-kit and c-kit ligand, and stromal derived factor-1alpha, in addition to matrix metalloproteinase-9, have emerged as critical factors that recruit progenitor cells to sites of arterial injury. While much progress has been made, several tasks remain, including the need for a more in-depth understanding of the mechanisms underlying progenitor cell recruitment, characterization of the involved progenitor cells, and finally validation that the observations made in these mouse models of disease are also applicable to human arterial restenosis.

Figure 1

Schematic of stem cell and progenitor cell classification. The hemangioblast is believed to be an embryonic precursor for HSCs and possibly also EPCs. HSCs differentiate into hematopoietic progenitors and then into the various blood cell lineages, but there is also evidence that HSCs can transdifferentiate into non-hematopoietic cells. MSCs are believed to differentiate into multiple mesenchymal lineages. Dotted grey lines indicate points that are still controversial.

Figure 2