Abstract 14480: Synthetic Smooth Muscle Cells are Derived from Multipotent Vascular Stem Cells Instead of Contractile Smooth Muscle Cells
Background: In the past few decades, it is generally believed that the de-differentiation of contractile SMCs results in proliferative synthetic SMCs upon vascular injury. However, the heterogeneous phenotypes and responses of SMCs in the vascular wall suggest that only a subpopulation of SMCs responds to vascular injury and participate in neointima formation. Currently, there is no definitive mechanism that clearly explains the heterogeneous SMCs phenotypes in diseased vessels. In addition, the possibility that synthetic SMCs might be SMC progenitors has never been investigated.
Methods & Results: Myh11-Cre/loxP-EGFP lineage tracing experiments showed that isolated synthetic SMCs were negative for EGFP, which indicated that they were not derived from contractile SMCs. Immunostaining and differentiation assay showed that synthetic SMCs at early stage (within 5 days of primary culture) are multipotent vascular stem cells (MVSCs), which can be characterized by various neural crest markers. MVSCs could spontaneously differentiate into contractile SMCs and can be induced into multiple neural and mesenchymal lineages. MVSCs isolated from arteries and veins showed identical global gene expression patterns as well as the multipotency as evidenced by DNA microarray and differentiation assay. Quantitative polymerase chain reaction showed that various growth factors significantly elevated matrix proteins expression in partially differentiated MVSCs (15 days of primary culture) but not undifferentiated MVSCs, suggesting “synthetic phenotype” of the partially differentiated MVSCs. Vascular injury model showed that upon vascular injuries, MVSCs were activated to proliferate and expanded into a major cell population (80%-90%) in neointima. Furthermore, MVSCs could be isolated from neointima and showed multipotency.
Conclusions: The previously identified “synthetic SMCs” are not derived from contractile SMCs. Instead, they are derived from a type of multipotent stem cells resident in blood vessel wall. The rapid proliferation and migration MVSCs instead of de-differentiation of contractile SMCs result in the neointima formation after vascular injury.
- © 2011 by American Heart Association, Inc.