Massa A, Perut F, Chano T, Woloszyk A, Mitsiadis T A, Avnet S, Baldini N
Istituto Ortopedico Rizzoli, Orthopaedic Pathophysiology and Regenerative Medicine Unit, Via di Barbiano 1/10, 40136 Bologna,
Eur Cell Mater. 2017 Apr 3;33:252-267. doi: 10.22203/eCM.v033a19.
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.
细胞群体中的干细胞部分会受到来自外部微环境刺激的精细调节。在这些刺激中，细胞外pH值（pHe）的降低可能发生在多种生理和病理状况下，包括缺氧和炎症。在本研究中，我们使用骨髓干细胞和牙髓干细胞，提供了证据表明细胞外酸中毒赋予间充质细胞干性的维持。事实上，连续21天暴露于低pHe（6.5 - 6.8）条件下会损害这两种细胞类型的成骨分化。此外，暴露于低pHe 1天至7天，会诱导干性相关基因和蛋白质的表达，促使细胞处于静止的G0警戒状态，并增强它们形成悬浮球的能力。用细胞外酸中毒预处理7天并不影响牙髓干细胞的分化潜能，因为当细胞在生理pHe条件下再次培养时，它们的多向分化潜能几乎未改变。我们的数据提供了证据证明细胞外酸中毒作为间充质细胞干性调节剂的作用。这种情况在全身性和局部骨状况中都很常见，因此突出了这一现象对于更好理解骨愈合和再生的相关性。
