Acidic Microenvironments Inhibit the Proliferation, Differentiation, and Bone Formation Potential of Human Adipose-derived Stem Cells

Abstract

Balanced local pH serves a vital role in extracellular microenvironment homeostasis. However, the impact of local pH disturbance on the proliferation, differentiation, and bone formation potential of human adipose-derived stem cells (ASCs) remain to be fully addressed. In the present study, we evaluated proliferation and multilineage differentiation ability in vitro by culturing human ASCs in mediums at pH 6.8 (acidic medium) and 7.4 (normal medium). The results indicated that the proliferation was markedly inhibited after 120 hours of culture in an acidic medium (p < 0.05). Additionally, osteogenic differentiation ability was also hampered by the acidic condition. Notably, adipogenic capacity was unaffected. ASCs were then seeded in Ultrafoam constructs and induced into chondrocytes and hypertrophic chondrocytes in vitro to verify the chondrogenic ability in acidic and normal medium. The normal condition group presented glycosaminoglycan (GAG) accumulation and large chondrocyte-shaped cells found in lacunae. In contrast, the acidic medium group showed no typical chondrocytes or GAG. When implanted subcutaneously in mice, there was no de novo bone tissue in the acidic cultured constructs when compared to the bone formation and blood vessel invasion of the normal pH group, which was consistent with the in vitro study. In conclusion, even minor changes in extracellular pH could significantly affect the proliferation and differentiation ability of ASCs. Thus, the control of extracellular pH condition is crucially important to successful chondrogenic priming, tissue engineering, and the study of chondrocyte physiology and functions. (Am J Transl Med 2020. 5(1):25-36).