Document details

Towards the Maturation and Characterization of Smooth Muscle Cells Derived from...

Author(s): Vazão, Helena cv logo 1 ; Neves, Ricardo Pires das cv logo 2 ; Grãos, Mário cv logo 3 ; Ferreira, Lino cv logo 4

Date: 2011

Persistent ID: http://hdl.handle.net/10316/15680

Origin: Estudo Geral - Universidade de Coimbra


Description
In this study we demonstrate that CD34+ cells derived from human embryonic stem cells (hESCs) have higher smooth muscle cell (SMC) potential than CD34− cells. We report that from all inductive signals tested, retinoic acid (RA) and platelet derived growth factor (PDGFBB) are the most effective agents in guiding the differentiation of CD34+ cells into smooth muscle progenitor cells (SMPCs) characterized by the expression of SMC genes and proteins, secretion of SMC-related cytokines, contraction in response to depolarization agents and vasoactive peptides and expression of SMC-related genes in a 3D environment. These cells are also characterized by a low organization of the contractile proteins and the contractility response is mediated by Ca2+, which involves the activation of Rho A/Rho kinase- and Ca2+/calmodulin (CaM)/myosin light chain kinase (MLCK)-dependent pathways. We further show that SMPCs obtained from the differentiation of CD34+ cells with RA, but not with PDGFBB, can be maturated in medium supplemented with endothelin-1 showing at the end individualized contractile filaments. Overall the hESC-derived SMCs presented in this work might be an unlimited source of SMCs for tissue engineering and regenerative medicine. Marie Curie-Reintegration Grant MIT-Portugal program Crioestaminal Associação Viver a Ciência Fundação para a Ciência e a Tecnologia (PTDC/SA-BEB/098468/2008 and PTDC/CTM/099659/2008 to L.F.; SFRH/BD/40077/2007 to H.V.)
Document Type Article
Language English
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