title: Mitochondrial Functional Changes Characterization in Young and Senescent Human Adipose Derived MSCs.
abstract: Mitochondria are highly dynamic organelles that in response to the cell's bio-energetic state continuously undergo structural remodeling fission and fusion processes. This mitochondrial dynamic activity has been implicated in cell cycle, autophagy, and age-related diseases. Adult tissue-derived mesenchymal stromal/stem cells present a therapeutic potential. However, to obtain an adequate mesenchymal stromal/stem cell number for clinical use, extensivein vitroexpansion is required. Unfortunately, these cells undergo replicative senescence rapidly by mechanisms that are not well understood. Senescence has been associated with metabolic changes in the oxidative state of the cell, a process that has been also linked to mitochondrial fission and fusion events, suggesting an association between mitochondrial dynamics and senescence. In the present work, we studied the mitochondrial structural remodeling process of mesenchymal stromal/stem cells isolated from adipose tissuein vitroto determine if mitochondrial phenotypic changes were associated with mesenchymal stromal/stem cell senescence. For this purpose, mitochondrial dynamics and oxidative state of stromal/stem cell were compared between young and old cells. With increased cell passage, we observed a significant change in cell morphology that was associated with an increase in β-galactosidase activity. In addition, old cells (population doubling seven) also showed increased mitochondrial mass, augmented superoxide production, and decreased mitochondrial membrane potential. These changes in morphology were related to slightly levels increases in mitochondrial fusion proteins, Mitofusion 1 (MFN1), and Dynamin-related GTPase (OPA1). Collectively, our results showed that adipose tissue-derived MSCs at population doubling seven developed a senescent phenotype that was characterized by metabolic cell changes that can lead to mitochondrial fusion.
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Stab
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Laura
authors.initials: L
authors.lastname: Martinez
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Grismaldo
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Lerma
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad JaverianaBogotá, Colombia; Institute for the Study of Inborn Errors of Metabolism, Faculty of Sciences, Pontificia Universidad JaverianaBogotá, Colombia.
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, Faculty of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Jhon J
authors.initials: JJ
authors.lastname: Sutachan
authors.affiliation: Department of Nutrition and Biochemistry, School of Sciences, Pontificia Universidad Javeriana Bogotá, Colombia.
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Albarracín
keywords: adipose derived mesenchymal stromal cells; fission and fusion; mitochondria; reactive oxygen species; senescence