Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells

Int J Mol Sci. 2019 Mar 4;20(5):1097. doi: 10.3390/ijms20051097.


A deeper understanding of the detailed mechanism of in vivo tissue healing is necessary for the development of novel regenerative therapies. Among several external factors, environmental pH is one of the crucial parameters that greatly affects enzyme activity and cellular biochemical reactions involving tissue repair and homeostasis. In this study, in order to analyze the microenvironmental conditions during bone healing, we first measured the pH in vivo at the bone healing site using a high-resolution fiber optic pH microsensor directly in femur defects and tooth extraction sockets. The pH was shown to decrease from physiological 7.4 to 6.8 during the initial two days of healing (inflammatory phase). In the same initial stages of the inflammatory phase of the bone healing process, mesenchymal stem cells (MSCs) are known to migrate to the healing site to contribute to tissue repair. Therefore, we investigated the effect of a short-term acidic (pH 6.8) pre-treatment on the stemness of bone marrow-derived MSCs (BMSCs). Interestingly, the results showed that pre-treatment of BMSCs with acidic pH enhances the expression of stem cell markers (OCT-4, NANOG, SSEA-4), as well as cell viability and proliferation. On the other hand, acidic pH decreased BMSC migration ability. These results indicate that acidic pH during the initial stages of bone healing is important to enhance the stem cell properties of BMSCs. These findings may enable the development of novel methods for optimization of stem cell function towards tissue engineering or regenerative medicine.

Keywords: acidic treatment; bone healing; mesenchymal stem cells; stemness.

MeSH terms

  • Acids / pharmacology*
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Regeneration / drug effects
  • Bone Regeneration / genetics*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cellular Microenvironment / drug effects
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Nanog Homeobox Protein / genetics
  • Octamer Transcription Factor-3 / genetics
  • Osteogenesis / drug effects*
  • Regenerative Medicine
  • Stage-Specific Embryonic Antigens / genetics
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Tissue Engineering / methods*
  • Wound Healing / genetics


  • Acids
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • Stage-Specific Embryonic Antigens
  • stage-specific embryonic antigen-4