The proliferation and differentiation of placental-derived multipotent cells into smooth muscle cells on fibrillar collagen
Journal
Biomaterials
Journal Volume
31
Journal Issue
15
Pages
4367-4375
Date Issued
2010
Author(s)
Abstract
Type I collagen constitutes a major portion of the extracellular matrix (ECM) in arterial wall and it is the major substrate for cell growth and differentiation. The goal of this study was to evaluate the differentiation and proliferation of placenta-derived multipotent cells (PDMCs) on polymerized type I collagen fibrils and monomer collagen. PDMCs grown on both polymerized collagen and monomer collagen with transforming growth factor (TGF)-beta treatment increases the expression of smooth muscle cell (SMC)-specific markers, including calponin, alpha-smooth muscle actin (alpha-SMA) and smooth muscle-myosin heavy chain (SM-MHC). Polymerized collagen increased the expressions of p21(CIP1) and p27(KIP1); decreased cyclin A, cyclin D1, cyclin-dependent protein kinase 2 (Cdk2); and led to G(0)/G(1) arrest in PDMCs. Furthermore, PDMC-differentiated SMCs exhibited significant collagen contractility in the presence or absence of endothelin-1 (ET-1) stimulation. By using specific inhibitors and small interfering RNA (siRNA), we demonstrated that p38 MAPK pathway and serum response factor (SRF)-DNA binding activity is critical for the polymerized collagen-induced PDMC differentiation into SMCs. Thus, polymerized collagen exhibits the great potential in inducing PDMCs differentiation into SMCs, and exerts anti-proliferative effect on PDMC-differentiated SMCs.
Type
journal article