title: Cell Expansion-Dependent Inflammatory and Metabolic Profile of Human Bone Marrow Mesenchymal Stem Cells.
abstract: Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in cultureviaplastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansionin vitromay be limited mainly due to "cell aging" related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity. We have exposed human MSCs after several passages to TLRs ligands and analyzed their inflammatory response. These cells responded to pro-inflammatory stimuli (i.e., NOS-2 expression) and to anti-inflammatory cytokines (i.e., HO1 and Arg1) until two expansions, rapidly declining upon subculture. Moreover, in the first passages, MSCs were capable to release IL1β, IL6, and IL8, as well as to produce active MMPs allowing them to migrate. Interestingly enough, after two passages, anaerobic glycolysis was enhanced releasing high levels of lactate to the extracellular medium. All these results may have important implications for the safety and efficacy of MSCs-based cell therapies.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Prieto
authors.affiliation: Instituto de Investigación Hospital Universitario La Paz Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Velasco
authors.affiliation: Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón Madrid, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Fernández-Santos
authors.affiliation: Servicio de Cardiología, Hospital Clínico de Salamanca Salamanca, Spain.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Sánchez
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Terrón
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín-Sanz
authors.affiliation: Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio MarañónMadrid, Spain; Facultad de Medicina, Universidad Complutense de Madrid, Ciudad UniversitariaMadrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández-Avilés
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Madrid, Spain.
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
keywords: bone marrow; cytokines; human; inflammation; stem cell