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Mitochondrial Respiration Regulates Proliferation, Micromotion, and Wound Healing Migration of Human Mesenchymal Stem Cells
Author(s) -
Lee Yu Wei,
Tung Tse Hua,
Gomez Sofia,
Lo Chun Min
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1300.10
Subject(s) - mesenchymal stem cell , mitochondrion , chemistry , wound healing , cell growth , oxidative phosphorylation , cell , extracellular , stem cell , respiration , biophysics , microbiology and biotechnology , biochemistry , biology , anatomy , immunology
Mitochondria plays an important role in human mesenchymal stem cell (hMSC) proliferation and differentiation. Carbonyl cyanide 4‐(trifluoromethoxy) phenylhydrazone (FCCP), which uncouples mitochondrial oxidative phosphorylation from the electron transport chain, is known to increase oxygen consumption rates. In this study, hMSCs derived from umbilical cord were chronically exposed to different concentrations of FCCP. Cell proliferation and mitochondrial activities were measure by CyQUANT® NF cell proliferation assay and Seahorse XF‐24 extracellular flux analyzer respectively. Compared with control group, chronic exposure of hMSCs to 1 μM and 3 μM FCCP for two days led to approximately 10% and 60% reduction of proliferation. Furthermore, chronic exposure of hMSCs to 3 μM FCCP for 20 hours significantly reduced their mitochondrial function. Electric cell‐substrate impedance sensing (ECIS) was also used to detect the alternation of hMSC micromotion and wound healing migration in response to different concentrations of FCCP treatment for 20 hours. The variance and energy of level 1 DWT (discrete wavelet transform) detail coefficients of the measured resistance time series at 4 kHz were calculated and the results demonstrated a dose‐dependent decrease from 1 μM to 3 μM FCCP, implying the dose‐dependent reduction of cell micromotion. For wound healing migration, the recovery resistance curves were fitted by sigmoid curve and the hill slope showed a dose‐dependent decline from 0.3 μM to 3 μM FCCP, indicating the decrease in migration rate. Moreover, dose dependent incline of the inflection points from 0.3 μM to 3 μM FCCP implied the increase of the half time for wound recovery migration. If the measured capacitance time series at 40 kHz were analyzed and compared with the previous resistance results, the variance and energy of level 1 DWT detail coefficients dose‐dependently decreased from 0.1 μM to 3 μM FCCP. Together, these results demonstrate that partial uncoupling of mitochondrial oxidative phosphorylation reduces proliferation, micromotion, and wound healing migration of hMSCs. Support or Funding Information This work was supported by the Ministry of Science and Technology, Taiwan. (Grant number: NSC 102‐2628‐B‐010‐010‐MY3)