Functional differences between healthy and diabetic endothelial cells on topographical cues

Cutiongco, Marie F.A.; Chua, Bryan; Neo, Dawn Jing Hui; Rizwan, Muhammad; Yim, Evelyn K.F.

doi:10.1016/j.biomaterials.2017.10.037

Cited by 24 publications

(20 citation statements)

References 77 publications

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“…Surprisingly, when comparing between the two chondrocyte cell types, we also observed enhancement of SOX9 and COL2A1 expression on 62 nm. Similar to other reports [ 6 , 22 , 51 , 52 ], our results highlight how cell response to topography is highly dependent on intracellular context, even between cells of the same functional type.…”

Section: Resultssupporting

confidence: 91%

“…topography or substrate rigidity not found in the natural cell niche) can powerfully change cell behavior by inducing cell signaling mechanisms through mechanotransduction [ 15 – 18 ]. Artificial biophysical environments have therefore been shown to preferentially direct mesenchymal stem cell differentiation [ 19 – 21 ], alter endothelial cell functionality [ 22 – 24 ] and change in neurogenic subtype [ 14 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Customizable, engineered substrates for rapid screening of cellular cues

et al. 2020

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Biophysical cues robustly direct cell responses and are thus important tools for in vitro and translational biomedical applications. High throughput platforms exploring substrates with varying physical properties are therefore valuable. However, currently existing platforms are limited in throughput, the biomaterials used, the capability to segregate between different cues and the assessment of dynamic responses. Here we present a multiwell array (3 × 8) made of a substrate engineered to present topography or rigidity cues welded to a bottomless plate with a 96-well format. Both the patterns on the engineered substrate and the well plate format can be easily customized, permitting systematic and efficient screening of biophysical cues. To demonstrate the broad range of possible biophysical cues examinable, we designed and tested three multiwell arrays to influence cardiomyocyte, chondrocyte and osteoblast function. Using the multiwell array, we were able to measure different cell functionalities using analytical modalities such as live microscopy, qPCR and immunofluorescence. We observed that grooves (5 μ m in size) induced less variation in contractile function of cardiomyocytes. Compared to unpatterned plastic, nanopillars with 127 nm height, 100 nm diameter and 300 nm pitch enhanced matrix deposition, chondrogenic gene expression and chondrogenic maintenance. High aspect ratio pillars with an elastic shear modulus of 16 kPa mimicking the matrix found in early stages of bone development improved osteogenic gene expression compared to stiff plastic. We envisage that our bespoke multiwell array will accelerate the discovery of relevant biophysical cues through improved throughput and variety.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Customizable, engineered substrates for rapid screening of cellular cues

et al. 2020

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“…[7][8][9][10] Of particular interest are engineered substrates with defined biophysical properties that can recapitulate the substrate rigidity or surface topographical cues present in the natural cell environment. 11,12 Precisely engineered topographical cues or substrate rigidities have been shown to preferentially direct mesenchymal stem cell differentiation, [13][14][15] alter endothelial cell functionality [16][17][18] and change in neurogenic subtype. 19,20 Testing of engineered substrates has long relied on the use of individual substrates assessed in tandem to screen for positive hits but is severely hindered in throughput.…”

mentioning

confidence: 99%

Customizable, engineered substrates for rapid screening of cellular cues

Huethorst

Cutiongco

Campbell

et al. 2019

Preprint

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Biophysical cues robustly direct cell responses and are thus important tools for in vitro and translational biomedical applications. High throughput platforms exploring substrates with varying physical properties are therefore valuable, however, currently existing platforms are limited in throughput, the biomaterials used, the capability to segregate between different cues and the assessment of dynamic cellular responses. Here we present a multiwell array (3x8) using a substrate engineered with patterns that present topography or rigidity cues welded to a bottomless plate with a 96-well format. Both the patterns on the engineered substrate and the well plate format can be easily customized, permitting systematic and efficient screening of biophysical cues. Here, we demonstrate three multiwell arrays patterned with a variety of topographical and mechanical cues (nano-grooves, soft pillars and nano pillars) tested with three different cell types. Using the multiwell array, we were able to measure cell functionality using analytical modalities such as live microscopy, qPCR and fluorescent immunochemistry. Cardiomyocytes cultured on 5µm grooves showed less variation in electrophysiology and contractile function. Nanopillars with 127 nm height, 100 nm diameter and 300 nm pitch showed improved chondrogenic maintenance from matrix deposition and chondrogenic gene expression. High aspect ratio pillars with an elastic shear modulus of 16 kPa mimicking the cortical bone altered cell adhesion, morphology, and increased expression of osteogenic genes. We have demonstrated the bespoke, controlled and highthroughput properties of the multiwell array that are currently unparalleled in the field today.

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“…Ç'ÿñóâàííÿ ðîë³ ñóäèííîãî åíäîòåë³þ ðîçâèâàëîñÿ ïðîòÿãîì îñòàíí³õ äâîõ äåñÿòèë³òü òà ä³éøëî äî ðîçóì³ííÿ òîãî, ùî â³í º äèíàì³÷íîþ ðåãóëþþ÷îþ ñèñòåìîþ òà â³ä³ãðàº êëþ÷îâó ðîëü ÿê ó ô³ç³îëîã³÷íèõ, òàê ïðè ïàòîëîã³÷íèõ ïðîöåñàõ [9,12]. Åíäîòå-ë³àëüí³ êë³òèíè âèêîíóþòü áàð'ºðíó ðîëü òà àêòèâíî ðåãóëþþòü òîíóñ ñóäèí, êðîâîîá³ã ³ ôóíêö³þ òðîì-áîöèò³â [1,4,9]. Åíäîòåë³àëüíà äèñôóíêö³ÿ (ÅÄÔ) ôîðìóºòüñÿ ïðè çàïàëåíí³ ñóäèí, àòåðîñêëåðîç³, ã³ïåðòîí³¿, êàðä³îì³îïàò³¿, ðåòèíîïàò³¿, íåéðîïàò³¿ [5,13].…”

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“…Ïðè ÖÄ ö³ëèé êàñêàä ïàòîëîã³÷íèõ ðåàêö³é ðîçãîðòàºòüñÿ â åíäîòåë³¿ ñóäèí, ÿê³ ïîòåðïàþòü â³ä ãëþêîçîòîêñè÷íîñò³, íàäì³ðíî¿ ä³¿ ñòèìóëþþ÷èõ ã³ïåðòåíçèâíèõ òà çàïàëüíèõ ôàêòîð³â, àêòèâàòîð³â òðîìáîóòâîðåííÿ, ³íòåíñèô³êàö³¿ îêèñíîãî ñòðåñó [1,8,11]. Ââàaeàºòüñÿ, ùî äî ðîçâèòêó ÅÄÔ ïðèçâîäÿòü òàê³ ÷èííèêè: 1) ï³äâèùåíèé îêèñëþâàëüíèé ñòðåñ ³ ñèñòåìíå çàïàëåííÿ; 2) äåãðàäàö³ÿ ³ ïðîë³ôå-ðàö³ÿ ãë³êîêàë³êñó; 3) ïîðóøåííÿ ì³aeêë³òèííèõ êîí-òàêò³â åíäîòåë³îöèò³â òà ãåìàòî-òêàíèííîãî áàð'ºðó; 4) ïîñèëåííÿ àäãåç³¿ ëåéêîöèò³â ³ åêñòðàâàçàö³ÿ; 5) ³íäóêö³ÿ ïðîêîàãóëÿíò³â ³ àíò³ô³áð³íîë³ò³÷íèõ ñèñòåì [3].…”

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Connection of the Endothelial Dysfunction Factors and Diabetes Mellitus 2 Type Severities

2018

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Relevance. In the case of diabetes mellitus (DM), a whole cascade of pathological reactions unfolds in the endothelium of the vessels that afflict glucose toxicity, excessive action of stimulating hypertension and inflammatory factors, thrombotic activators, and the intensification of oxidative stress, which leads to the formation of endothelial dysfunction (EDF). On the other hand, the damaged endothelium itself is included in the pathogenesis of diabetes and causes the development of further violations. Objective: to investigate the association of EDF factors: endothelin 1 (ET1), endothelial NO-synthase (eNOS), nitric oxide (NO), tumor necrosis factor (TNFα), and diene conjugates (DC) with severity of type 2 diabetes. Materials and methods. Data were used for 152 hospital patients with type 2 diabetes at the age from 34 to 80 years (53.9±8.4 years). Women were 95 (62.5%), men – 57 (37.5%). According to the degree of severity of patients was divided into three groups: 1st (37.5% of patients) – the average stage in the compensation stage (HbA1s 7-9%), 2nd (41.4%) – the average stage in the stage of decompensation (HbA1s more than 9%), 3rd (21,1%) – a severe degree in the stage of decompensation. The control group included 95 practically healthy individuals. The plasma levels of the blood were determined by the enzyme-linked method: ЕТ1 (Biomedica Immunoassays, Austria), eNOS (BCM Diagnostics, USA) і TNFα (Bender Medsystems, Austria). The level of blood NO and DC were determined biochemically (spectrophotometer Specord, Germany). Statistica 10 (StatSoft, Inc., USA) was used to statistically process the data obtained. Results. Levels of EDF factors depended on the severity of DM 2 type. Thus, the level of ETI in patients exceeded control in 3.7-4.7 times (p<0.001) with the maximum values in the 2nd and 3rd groups; also increased blood levels of NO (1.4-1.5 times; p<0.001). The highest increase was observed in TNFα levels (4.2-6.5 times; p<0.001) and DC (2.3-2.7 times; p<0.001). The blood content of eNOS in the patients' groups was lower when compared with control (1.3-1.9 times; p<0.001). Single-factor regression analysis showed that ET1 caused high glycemia, albuminuria, increased the degree of decompensation of DM 2 type and the degree of diabetic nephropathy. NO accumulation in the blood affects the decrease in glomerular filtration rate and the deterioration of renal function. TNFα and DC contributed to almost all key indicators of DM 2 type, which had a synergistic effect with other EDF factors. Conclusion. Factors of EDF are closely linked with clinical and laboratory indicators of severity of DM 2 type, which highlights them in the pathogenesis of the disease.

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Functional differences between healthy and diabetic endothelial cells on topographical cues

Cited by 24 publications

References 77 publications

Customizable, engineered substrates for rapid screening of cellular cues

Customizable, engineered substrates for rapid screening of cellular cues

Customizable, engineered substrates for rapid screening of cellular cues

Connection of the Endothelial Dysfunction Factors and Diabetes Mellitus 2 Type Severities

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