Smooth Muscle Cell Plasticity: Fact or Fiction?
More than 50 years ago, smooth muscle cells (SMC) of the carotid artery were shown to undergo "de-differentiation" upon ligation injury.1 Since this classic study, scores of research groups have used a variety of in vivo and in vitro model systems as well as numerous clinical studies to demonstrate the conversion of normally contractile vascular SMC to a less differentiated state of proliferation, migration, and exuberant extracellular matrix secretion, a process generally referred to as phenotypic modulation or plasticity [reviewed in 2-6]. Such changes in vascular SMC phenotype are thought to underlie many vascular occlusive diseases. However, in a recent issue of Nature Communications, Tang et al7 provide data from in vitro cell culture, flow cytometry, and lineage tracing experiments which they believe directly challenge this long-standing and widely accepted paradigm. Specifically, these authors contend that: (1) differentiated (SM myosin heavy chain, SM MHC+) vascular SMC are incapable of proliferation either in vivo in response to injury or in vitro in cell culture; (2) within the media of mature blood vessels there exists a small population (<10%) of undifferentiated (SM MHC-) cells that activate markers of mesenchymal stem cells, including Sox17, Sox10, and S100β, and proliferate to completely reconstitute medial cells in response to vascular injury; and (3) these so-called medial-derived multi-potential vascular stem cells (MVSC) also proliferate and express several mesenchymal stem cell markers when placed in cell culture, and can be induced to differentiate into neural, chondrogenic, and SMC lineages with appropriate culture methods. The authors' bold conclusion that "MVSC activation and differentiation, instead of SMC de-differentiation, results in the proliferative and synthetic cells in the vascular wall," if true, would have a huge impact on our understanding of the role of SMC in vascular injury-repair and disease. Since an implicit aspect of the authors' claims is that previous studies have been conducted on MVSC, not SMC, it also potentially impacts conclusions from thousands of papers using cultured SMC as model systems. However, close examination of their results, which are in direct contradiction to a large body of published research, reveals a number of misinterpretations, overstatements, and technical deficiencies which seriously undermine most of their major conclusions as discussed further in this Perspective. [Extract]
- Accepted October 18, 2012.
- Copyright © 2012, American Heart Association