- In the library
- 3 works, named in 12 passages elsewhere
Depolarization and fat differentiation
In the 2008 study, human mesenchymal stem cells were grown in adipogenic medium with 80 mM extracellular potassium added to depolarize them. Expression of the fat marker LPL was far lower than in untreated cells on Days 2, 7 and 141. Oil Red O staining showed only tiny lipid droplets at the cell edges, and absorbance fell 8.7-fold. LPL stayed lower at Day 22, so suppression lasted about three weeks2. Ouabain at 10 nM also suppressed differentiation, though less strongly, and some cells later recovered and formed lipid droplets3.
Variation between donors
The 2015 paper began from a gap: earlier work had not systematically assessed how much hMSC responses to bioelectric signals differ between people4. The authors tested five donors with high potassium. In cells pre-differentiated into osteoblasts, ALPL expression was unchanged or slightly raised after treatment. ALP enzyme activity proved an inconsistent osteogenic marker, since osteogenic cells showed the same, higher or lower activity than undifferentiated cells depending on the donor5. Depolarization generally had no significant effect on this activity in four of five donors.
Use by later authors
The 2016 genome-wide study, with Sundelacruz among the authors, stated that no systematic analysis of transcriptional change after steady depolarization in vivo had been done6. Later reviews cite the earlier work on stem cells. Yang and Brackenbury cite Sundelacruz et al. (2009) for the need for a hyperpolarized potential during stem cell maturation7. Abdul Kadir and colleagues read the experiments as showing that forced depolarization keeps cells in a stem-cell-like state8.
On Days 2, 7, and 14, samples treated with 80 mM K+ (denoted AD-80K) had significantly lower LPL expression compared to untreated AD samples
Sundelacruz S, Levin M, Kaplan DL, 2008 · Membrane potential controls adipogenic and osteogenic differentiation of… · open at passage 12These results demonstrate that exposure to 80 mM extracellular K+, which depolarizes hMSCs, can suppress AD differentiation
Sundelacruz S, Levin M, Kaplan DL, 2008 · Membrane potential controls adipogenic and osteogenic differentiation of… · open at passage 12Therefore, treatment with 10 nM ouabain also suppresses AD differentiation, although not to the same degree as treatment with 80 mM K+.
Sundelacruz S, Levin M, Kaplan DL, 2008 · Membrane potential controls adipogenic and osteogenic differentiation of… · open at passage 14However, to date, efforts toward this end have not included a systematic assessment of the heterogeneity of hMSC response to bioelectric signals
Sundelacruz S, Levin M, Kaplan DL, 2015 · Comparison of the depolarization response of human mesenchymal stem cells from… · open at passage 4we found ALPL activity to again be an inconsistent osteogenic marker: osteogenic cells were found to have the same, increased, or decreased enzyme activity relative to undifferentiated cells in the five donors
Sundelacruz S, Levin M, Kaplan DL, 2015 · Comparison of the depolarization response of human mesenchymal stem cells from… · open at passage 19However, no systematic analysis has been performed to identify and integrate genome‐wide transcriptional changes following steady‐state depolarization in vivo
Pai VP, Martyniuk CJ, Echeverri K, Sundelacruz S, Kaplan…, 2016 · Genome-wide analysis reveals conserved transcriptional responses downstream of… · open at passage 4In particular, a hyperpolarized Vm is required during stem cell maturation (Sundelacruz et al., 2009).
Yang M, Brackenbury WJ, 2013 · Membrane potential and cancer progression · open at passage 23The importance of the membrane potential in differentiation can be seen from the experiments of Sundelacruz et al. (2008) and Lange et al. (2011) where forced depolarization maintains cells in a stem-cell like state.
Abdul Kadir L, Stacey M, Barrett-Jolley R, 2018 · Emerging Roles of the Membrane Potential: Action Beyond the Action Potential · open at passage 22
2008
2008 · read
2015
2015 · read
2016
2016 · read