TY - JOUR
T1 - Acidic pre-conditioning enhances the stem cell phenotype of human bone marrow stem/progenitor cells
AU - Hazehara-Kunitomo, Yuri
AU - Hara, Emilio Satoshi
AU - Ono, Mitsuaki
AU - Aung, Kyaw Thu
AU - Komi, Keiko
AU - Pham, Hai Thanh
AU - Akiyama, Kentaro
AU - Okada, Masahiro
AU - Oohashi, Toshitaka
AU - Matsumoto, Takuya
AU - Kuboki, Takuo
N1 - Funding Information:
Funding: “This research was funded by the Japan Society for the Promotion of Science, grant numbers [JP18K19646, JP17H04392]” and “The APC was funded by JSPS Grant number [JP18K19646]”.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - Acidic treatment
KW - Bone healing
KW - Mesenchymal stem cells
KW - Stemness
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U2 - 10.3390/ijms20051097
DO - 10.3390/ijms20051097
M3 - Article
C2 - 30836626
AN - SCOPUS:85062639551
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 5
M1 - 1097
ER -