Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series

Bodmer, James E.; English, Anthony E.; Brady, M.C.; Blackwell, Ken; Haxhinasto, Kari; Fotedar, Sunaina; Borgman, Kurt; Bai, Er‐Wei; Moy, Alan B.

doi:10.1152/ajpcell.00103.2005

Cited by 10 publications

(12 citation statements)

References 31 publications

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“…Diabetic PDCs were found to proliferate slightly better than diabetic BMSCs, but underwent even poorer osteogenic differentiation than diabetic BMSCs in normal glucose osteogenic media. Although it was previously shown that restoring normal insulin levels could improve bone quality in T1DM patients [42], early intervention is needed to prevent detrimental “metabolic memory” caused by hyperglycemia [43]. Our observation that skeletal progenitors isolated from T1DM rats with poorly controlled blood glucose exhibit significant cellular impairments in normal glucose cultures supports that restoring normal blood glucose alone may not be sufficient in rescuing skeletal comorbidities of T1DM.…”

Section: Discussionmentioning

confidence: 50%

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

et al. 2017

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BackgroundPoor bone quality, increased fracture risks, and impaired bone healing are orthopedic comorbidities of type 1 diabetes (T1DM). Standard osteogenic growth factor treatments are inadequate in fully rescuing retarded healing of traumatic T1DM long bone injuries where both periosteal and bone marrow niches are disrupted. We test the hypotheses that osteogenesis of bone marrow-derived stromal cells (BMSCs) and periosteum-derived cells (PDCs), two critical skeletal progenitors in long bone healing, are both impaired in T1DM and that they respond differentially to osteogenic bone morphogenetic proteins (BMPs) and/or insulin-like growth factor-1 (IGF-1) rescue.MethodsBMSCs and PDCs were isolated from Biobreeding Diabetes Prone/Worcester rats acquiring T1DM and normal Wistar rats. Proliferation, osteogenesis, and adipogenesis of the diabetic progenitors were compared with normal controls. Responses of diabetic progenitors to osteogenesis rescue by rhBMP-2/7 heterodimer (45 or 300 ng/ml) and/or rhIGF-1 (15 or 100 ng/ml) in normal and high glucose cultures were examined by alizarin red staining and qPCR.ResultsDiabetic BMSCs and PDCs proliferated slower and underwent poorer osteogenesis than nondiabetic controls, and these impairments were exacerbated in high glucose cultures. Osteogenesis of diabetic PDCs was rescued by rhBMP-2/7 or rhBMP-2/7 + rhIGF-1 in both normal and high glucose cultures in a dose-dependent manner. Diabetic BMSCs, however, only responded to 300 ng/nl rhBMP-2/7 with/without 100 ng/ml rhIGF-1 in normal but not high glucose osteogenic culture. IGF-1 alone was insufficient in rescuing the osteogenesis of either diabetic progenitor. Supplementing rhBMP-2/7 in high glucose osteogenic culture significantly enhanced gene expressions of type 1 collagen (Col 1), osteocalcin (OCN), and glucose transporter 1 (GLUT1) while suppressing that of adipogenic marker peroxisome proliferator-activated receptor gamma (PPARγ) in diabetic PDCs. The same treatment in high glucose culture only resulted in a moderate increase in Col 1, but no significant changes in OCN or GLUT1 expressions in diabetic BMSCs.ConclusionsThis study demonstrates more effective osteogenesis rescue of diabetic PDCs than BMSCs by rhBMP-2/7 with/without rhIGF-1 in a hyperglycemia environment, underscoring the necessity to tailor biochemical therapeutics to specific skeletal progenitor niches. Our data also suggest potential benefits of combining growth factor treatment with blood glucose management to optimize orthopedic therapeutic outcomes for T1DM patients.

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Section: Discussionmentioning

confidence: 50%

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

et al. 2017

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“…A numerical analysis was used to calculate specific cell-cell and cell-substrate adhesion and C m on the basis of the measured transcellular impedance recorded by the ECIS system using a model described elsewhere (19,22,24) and determined by computer algorithms recently described in complete detail elsewhere (3). Briefly, the total impedance across a cell-covered electrode is composed of the impedance created between the ventral surface of the cell and the electrode (␣), the impedance created between cells (R b), the transcellular impedance created from transcellular current conduction (Zm), and the impedance of a naked electrode (Zn).…”

Section: Materials Humanmentioning

confidence: 99%

“…The computer algorithms resolve measurements of TER into measurements of cell-cell adhesion (R b ), cell-matrix adhesion (␣), and membrane capacitance (C m ). Additionally, these computer algorithms calculate the error of the numerical analysis, which provides an assessment of model stability and reliability (3).…”

mentioning

confidence: 99%

Growth factor- and heparin-dependent regulation of constitutive and agonist-mediated human endothelial barrier function

Moy¹,

Blackwell²,

Wu³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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We report functional differences in constitutive and agonist-mediated endothelial barrier function between cultured primary and Clonetics human umbilical vein endothelial cells (pHUVEC and cHUVEC) grown in soluble growth factors and heparin. Basal transendothelial resistance (TER) was much lower in pHUVEC than in cHUVEC grown in medium supplemented with growth factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and human epithelial growth factor (EGF), and heparin. On the basis of a numerical model of TER, the increased basal TER in cHUVEC was due to effects on cell-matrix adhesion and membrane capacitance. Heparin and bFGF increased constitutive TER in cultured pHUVEC, and heparin mediated additional increases in constitutive TER in pHUVEC supplemented with bFGF. EGF attenuated bFGF-mediated increases in TER. On the basis of the numerical model, in contrast to cHUVEC, heparin and bFGF augmented TER through effects on cell-cell adhesion and membrane capacitance in pHUVEC. Thrombin mediated quantitatively greater amplitude and a more sustained decline in TER in cultured cHUVEC than pHUVEC. Thrombin-mediated barrier dysfunction was attenuated in pHUVEC conditioned in EGF in the presence or absence of heparin. Thrombin-mediated barrier dysfunction was also attenuated when monolayers were exposed to low concentrations of heparin and further attenuated in the presence of bFGF. cAMP stimulation mediated differential attenuation of thrombin-mediated barrier dysfunction between pHUVEC and cHUVEC. VEGF displayed differential effects in TER in serum-free medium. Taken together, these data demonstrate marked differential regulation of constitutive and agonist-mediated endothelial barrier function in response to mitogens and heparin stimulation.

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“…These model parameters were then extracted by iteratively least–square–fitting the function to the measured impedance–related RMS output voltages shown in Fig. 1 (Bodmer et al, 2005). A multiple–step–fitting approach was employed in our multi–parameter extraction process in order to minimize the errors (Gordon et al, 1989; Lo et al, 1995).…”

Section: Data Fitting With the Equivalent Circuit Modelmentioning

confidence: 99%

Response characteristics of single-cell impedance sensors employed with surface-modified microelectrodes

Thein

Asphahani

Cheng

et al. 2010

Biosensors and Bioelectronics

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The underlying sensing mechanism of single-cell-based integrated microelectrode array (IMA) biosensors was investigated via experimental and modeling studies. IMA chips were microfabricated and single-cell-level manipulation was achieved through surface chemistry modification of IMA chips. Individual fibroblast cells (NIH3T3) were immobilized on either lysine-arginine-glycineaspartic acid (KRGD) short peptide-modified or fibronectin extracellular-cell-adhesion-moleculemodified microelectrodes to record the impedance variations of cell-electrode heterostructure over a frequency range of 1 to 10 kHz. By fitting experimental data to an application-specific single-celllevel equivalent circuit model, important sensing parameters, including specific cell membrane capacity, cell membrane resistivity, and averaged cell-to-substrate separation, were determined. It was demonstrated that biofunctionalization of planar microelectrode surface by covalently linking short peptides or fibronectin molecules could achieve strong or tight cell adhesion (with an estimated averaged cell-to-substrate separation distance of 11-16 nm), which, in turn, improves the transduced electrical signal from IMA chips. Analyses on frequency-dependent characteristics of single-cellcovered microelectrode impedance and of IMA sensor circuitry response have revealed an addressable frequency band wherein electrical properties of single cells can be distinctively determined and monitored for cellular biosensing applications. The presented work addresses some major limitations in single-cell-based biosensing schemes, i.e. the manipulation of a single cell, the transduction of weak biological signals, and the implementation of a proper model for data analysis, and demonstrates the potential of IMA devices as single-cell biosensors.

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Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series

Abstract: . Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series.

Cited by 10 publications

References 31 publications

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

Growth factor- and heparin-dependent regulation of constitutive and agonist-mediated human endothelial barrier function

Response characteristics of single-cell impedance sensors employed with surface-modified microelectrodes

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