Open AccessDifferentiation of Bone Marrow Mesenchymal Stem Cells into the Smooth Muscle Lineage by Blocking ERK/MAPK Signaling Pathway
Author(s) -
Kenichi Tamama,
Chandan K. Sen,
Alan Wells
Publication year - 2008
Publication title -
stem cells and development
Language(s) - English
Resource type - Journals
eISSN - 1557-8534
pISSN - 1547-3287
DOI - 10.1089/scd.2007.0155
Subject(s) - biology , mesenchymal stem cell , microbiology and biotechnology , mapk/erk pathway , myosin , myocardin , mek inhibitor , stem cell , cellular differentiation , caldesmon , bone marrow , endocrinology , immunology , medicine , signal transduction , serum response factor , gene expression , genetics , biochemistry , gene , calmodulin , enzyme
Smooth muscle cells (SMCs) are major components of blood vessels and other hollow visceral organs required for tissue engineering of these organs. This study aims to evaluate whether adult bone marrow-derived mesenchymal stem cells (BMMSCs), multipotent cells, can be converted into SMCs. We examined the ERK/MAPK pathway as it exerts anti-myogenic signals in SMCs. Undifferentiated BMMSCs express most SMC marker genes, albeit mainly at low levels, except smooth muscle myosin heavy chain (SMMHC), the most definitive marker of differentiated SMC. The treatment of BMMSC with MEK inhibitor up-regulated the expression of alpha-smooth muscle actin (ASMA), h-caldesmon, and SMMHC in BMMSC in low serum condition. MEK inhibitor-treated BMMSC also contracted a collagen gel in response to endothelin. Interestingly, inhibition of MEK induced myocardin expression in BMMSC. In conclusion, BMMSCs treated MEK inhibitor gain a SMC-like phenotype with ligand-induced cell contractility to endothelin in vitro. This approach has obvious implications for cell therapeutics and tissue engineering of hollow visceral organs such as blood vessels.