eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2017   Volume No 33 – pages 252-267

Title: The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro

Authors: A Massa, F Perut, T Chano, A Woloszyk, TA Mitsiadis, S Avnet, N Baldini

Address: Istituto Ortopedico Rizzoli, Orthopaedic Pathophysiology and Regenerative Medicine Unit, Via di Barbiano 1/10, 40136 Bologna, Italy

E-mail: nicola.baldini at

Key Words: mesenchymal stem cells, dental pulp stem cells, extracellular pH, stemness, osteogenic differentiation.


Publication date: April 3rd 2017

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.

Article download: Pages 252-267(PDF file)