title: The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro.
abstract: The stem cell fraction of a cell population is finely tuned by stimuli from the external microenvironment. Among these stimuli, a decrease of extracellular pH (pHe) may occur in a variety of physiological and pathological conditions, including hypoxia and inflammation. In this study, by using bone marrow stem cells and dental pulp stem cells, we provided evidence that extracellular acidosis endows the maintenance of stemness in mesenchymal cells. Indeed, continuous exposure for 21 d to low pHe (6.5-6.8) conditions impaired the osteogenic differentiation of both cell types. Moreover, the exposure to low pHe, for 1 and up to 7 d, induced the expression of stemness-related genes and proteins, drove cells to reside in the quiescent G0 alert state and enhanced their ability to form floating spheres. The pre-conditioning with extracellular acidosis for 7 d did not affect the differentiation potential of dental pulp stem cells since, when the cells were cultured again at physiological pHe, their multilineage potential was almost unmodified. Our data provided evidence of the role of extracellular acidosis as a modulator of the stemness of mesenchymal cells. This condition is commonly found both in systemic and local bone conditions, hence underlining the relevance of this phenomenon for a better comprehension of bone healing and regeneration.
authors.forename: A
authors.initials: A
authors.lastname: Massa
authors.forename: F
authors.initials: F
authors.lastname: Perut
authors.forename: T
authors.initials: T
authors.lastname: Chano
authors.forename: A
authors.initials: A
authors.lastname: Woloszyk
authors.forename: T A
authors.initials: TA
authors.lastname: Mitsiadis
authors.forename: S
authors.initials: S
authors.lastname: Avnet
authors.affiliation: Istituto Ortopedico Rizzoli, Orthopaedic Pathophysiology and Regenerative Medicine Unit, Via di Barbiano 1/10, 40136 Bologna, Italy.nicola.baldini@ior.it.
authors.forename: N
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D003782:Dental Pulp / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010012:Osteogenesis; D013234:Stem Cells / Q000166:cytology
chemical_list: D015415:Biomarkers