title: Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation.
abstract: Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell-substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations. Superlots composed of hASCs from young (aged 24-36 years), middle-aged (aged 48-55 years), and elderly (aged 60-81 years) donors were seeded on gold electrode arrays. Complex impedance measurements were taken throughout proliferation and osteogenic differentiation. During osteogenic differentiation, four impedance phases were identified: increase, primary stabilization, drop phase, and secondary stabilization. Matrix deposition was first observed 48-96 hours after the impedance maximum, indicating, for the first time, that ECIS can identify morphological changes that correspond to late-stage osteogenic differentiation. The impedance maximum was observed at day 10.0 in young, day 6.1 in middle-aged, and day 1.3 in elderly hASCs, suggesting that hASCs from younger donors require a longer time to differentiate than do hASCs from older donors, but young hASCs proliferated more and accreted more calcium long-term. This is the first study to use ECIS to predict osteogenic potential of multiple hASC populations and to show that donor age may temporally control onset of osteogenesis. These findings could be critical for development of patient-specific bone tissue engineering and regenerative medicine therapies. Stem Cells Translational Medicine 2017;6:502-511.
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Nordberg
authors.affiliation: Edward P. Fitts Department of Industrial and Systems Engineering, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Jianlei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Griffith
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Frank
authors.affiliation: Edward P. Fitts Department of Industrial and Systems Engineering, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Binil
authors.initials: B
authors.lastname: Starly
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA.|University of Missouri College of Engineering, Columbia, Missouri, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Loboa
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D058266:Dielectric Spectroscopy / Q000379:methods*; D017097:Electric Impedance; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
keywords: Adipose stem cells; Bioimpedance; Electrical cell-substrate impedance spectroscopy; Osteogenesis