We ask the question whether cardiac cells, separated by a soft solid medium, can interact with one another mechanically, and if so, then how does the interaction depend on cell–cell separation, and the stiffness of the medium. First, we show that cardiac cells can be stimulated by a mechanical signal alone. We culture primary chicken embryonic cardiomyocytes on a 2D soft substrate. A mechanical probe is used to apply local cyclic stretch on the substrate near quiescent cells (cells not beating). Within 10 cycles of stretch, the cells begin to beat, and continue to do so for hours after the stimulation, while control non-beating cells remain quiescent. Next, we show that a beating cardiac cell (instead of the probe) can stimulate a neighbor. Our 2D culture of cardiomyocytes on a deformable soft substrate (0.5–1 kPa) shows that closer the cells are as a pair, higher is the probability of both of them beating over longer time. This probability is much higher than that of both cells beating as a pair when they are cultured on a harder substrate (47 kPa), or the probability of a single cell beating on the same soft substrate (0.5–1 kPa). The cell–cell interaction, namely, the stretch induced by one contractile cell onto another is modeled using the principles of continuum mechanics. The close correspondence between the predicted cell–cell interaction and the experimental observations suggests that cardiac cells are mechanically coupled through the deformable substrate, and that the coupling decreases with increasing distance between them and the substrate stiffness. The quantitative analysis and the experimental results provide a biophysical basis for the understanding of cell–cell interaction in cardiac tissue through the deformation field of the in vivo soft microenvironment.
The aim of this review is to provide an overview of physiologically relevant microengineered lung-on-a-chip (LoC) platforms for a variety of different biomedical applications with emphasis on drug screening. First, a brief outline of lung anatomy and physiology is presented followed by discussion of the lung parenchyma and its extracellular matrix. Next, we point out the technical challenges in recapitulating the complexity of lung in conventional static two-dimensional microenvironments and the need for alternate lung platforms. The importance of scaling laws is also emphasized in designing these in vitro microengineered lung platforms. The review then discusses current LoC platforms that have been used for testing the efficacy of drugs or as model systems for investigating disorders of the lung parenchyma. Finally, the design parameters in developing an ideal physiologically relevant LoC platform are presented. As this emerging field of organ-on-a-chip can serve an alternative platform for animal testing of drugs or modeling human diseases in vitro, it has significant potential to impact the future of pharmaceutical research.
Journal Article Patterning the differentiation of C2C12 skeletal myoblasts Get access Piyush Bajaj, Piyush Bajaj Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Fax: +1 217 244-6375; Tel: +1 217 333-30972000 Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 North Wright Street, Urbana, IL 61801, USA Search for other works by this author on: Oxford Academic Google Scholar Bobby Reddy, Jr., Bobby Reddy, Jr. 2000 Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 North Wright Street, Urbana, IL 61801, USADepartment of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Search for other works by this author on: Oxford Academic Google Scholar Larry Millet, Larry Millet 2000 Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 North Wright Street, Urbana, IL 61801, USADepartment of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Search for other works by this author on: Oxford Academic Google Scholar Chunan Wei, Chunan Wei Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Search for other works by this author on: Oxford Academic Google Scholar Pinar Zorlutuna, Pinar Zorlutuna Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Fax: +1 217 244-6375; Tel: +1 217 333-30972000 Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 North Wright Street, Urbana, IL 61801, USANow at Harvard-MIT's Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Search for other works by this author on: Oxford Academic Google Scholar Gang Bao, Gang Bao Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USA Search for other works by this author on: Oxford Academic Google Scholar Rashid Bashir Rashid Bashir Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Fax: +1 217 244-6375; Tel: +1 217 333-30972000 Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 North Wright Street, Urbana, IL 61801, USADepartment of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA E-mail: rbashir@illinois.edu Search for other works by this author on: Oxford Academic Google Scholar Integrative Biology, Volume 3, Issue 9, September 2011, Pages 897–909, https://doi.org/10.1039/c1ib00058f Published: 15 August 2011 Article history Received: 09 June 2011 Accepted: 29 July 2011 Published: 15 August 2011
The kidney is a major clearance organ of the body and is responsible for the elimination of many xenobiotics and prescription drugs. With its multitude of uptake and efflux transporters and metabolizing enzymes, the proximal tubule cell (PTC) in the nephron plays a key role in the disposition of xenobiotics and is also a primary site for toxicity. In this minireview, we first provide an overview of the major transporters and metabolizing enzymes in the PTCs responsible for biotransformation and disposition of drugs. Next, we discuss different cell sources that have been used to model PTCs in vitro, their pros and cons, and their characterization. As current technology is inadequate to evaluate reliably drug disposition and toxicity in the kidney, we then discuss recent advancements in kidney microphysiological systems (MPS) and the need to develop robust in vitro platforms that could be routinely used by pharmaceutical companies to screen compounds. Finally, we discuss the new and exciting field of stem cell–derived kidney models as potential cell sources for future kidney MPS. Given the push from both regulatory agencies and pharmaceutical companies to use more predictive "human-like" in vitro systems in the early stages of drug development to reduce attrition, these emerging models have the potential to be a game changer and may revolutionize how renal disposition and kidney toxicity in drug discovery are evaluated in the future.
Background: Nd:YAG laser is non-invasive and effective means to deal with the posterior capsule opacification.However safe it may have some inherent complications. Rise of intraocular pressure is frequently encountered and incompletely understood complication of YAG laser capsulotomy and documented with conflicting results.Aims and Objective: To assess the efficacy of Nd: YAG laser capsulotomy in term of visual outcome(Best Corrected Visual Acuity) and also study the changes in IOP after the procedure.Materials and Methods: Study evaluated the changes in IOP and visual acuity after Nd-YAG laser capsulotomy in 100 eyes with significant PCO after uncomplicated cataract surgery with IOL implantation. Complete ocular examination including visual acuity, anterior segment examination with slit lamp, fundus and applanation tonometry were performed pre and post-laser in all cases. Posterior capsulotomy was done with VISULAS YAG III Q-switched Nd: YAG laser machine by ZEISS. IOP was recorded before and then at 1hour, 1 Day, 1 week and 1 month post-laser in order to determine the IOP changes.Results: Pre-laser visual acuity ranged from 1/60 to 6/12. Results showed statistically significant improvement in BCVA with 70% patients had BCVA 6/6, 21% had BCVA 6/9 and 8% having BCVA 6/12 post-laser at 1 month. It was observed that 36% of the patients showed no change in IOP while 64% patients showed elevated IOP. Among these 59% patients show rise in IOP that was ≤5 mm Hg while only 5% of the patients had a rise of more than IOP >5 mm Hg. Most of these patients achieved their baseline IOP within 1 day and only 7 % patient had rise in IOP compared to baseline IOP on day 1. None of the patients show elevated IOP after 1 week.Conclusion: Our study showed that Nd: YAG laser posterior capsulotomy provided excellent results in terms of visual improvement and most of the patients had a rise of <5mm Hg which was transient in nature and routine antiglaucoma medication may not be needed in all the patient undergoing Nd;Yag capsulotomy, however caution should be exercised in glaucomatous, aphakic, high myopic and other high risk patients.Asian Journal of Medical Sciences Vol.8(5) 2017 93-97
Microphysiological systems are an emerging area of in vitro drug development, and their independent evaluation is important for wide adoption and use. The primary goal of this study was to test reproducibility and robustness of a renal proximal tubule microphysiological system, OrganoPlate 3-lane 40, as an in vitro model for drug transport and toxicity studies. This microfluidic model was compared with static multiwell cultures and tested using several human renal proximal tubule epithelial cell (RPTEC) types. The model was characterized in terms of the functional transport for various tubule-specific proteins, epithelial permeability of small molecules (cisplatin, tenofovir, and perfluorooctanoic acid) versus large molecules (fluorescent dextrans, 60-150 kDa), and gene expression response to a nephrotoxic xenobiotic. The advantages offered by OrganoPlate 3-lane 40 as compared with multiwell cultures are the presence of media flow, albeit intermittent, and increased throughput compared with other microfluidic models. However, OrganoPlate 3-lane 40 model appeared to offer only limited (eg, MRP-mediated transport) advantages in terms of either gene expression or functional transport when compared with the multiwell plate culture conditions. Although OrganoPlate 3-lane 40 can be used to study cellular uptake and direct toxic effects of small molecules, it may have limited utility for drug transport studies. Overall, this study offers refined experimental protocols and comprehensive comparative data on the function of RPETCs in traditional multiwell culture and microfluidic OrganoPlate 3-lane 40, information that will be invaluable for the prospective end-users of in vitro models of the human proximal tubule.
In vitro models that can faithfully replicate critical aspects of kidney tubule function such as directional drug transport are in high demand in pharmacology and toxicology. Accordingly, development and validation of new models is underway. The objective of this study was to characterize physiologic and transport functions of various sources of human renal proximal tubule epithelial cells (RPTECs). We tested telomerase reverse transcriptase 1 (TERT1)-immortalized RPTECs, including organic anion transporter 1 (OAT1)-, organic cation transporter 2 (OCT2)-, or OAT3-overexpressing variants and primary RPTECs. Cells were cultured on transwell membranes in static (24-well transwells) and fluidic (transwells in PhysioMimix T12 organ-on-chip with 2 μL/s flow) conditions. Barrier formation, transport, and gene expression were evaluated. We show that 2 commercially available primary RPTECs were not suitable for studies of directional transport on transwells because they formed a substandard barrier even though they exhibited higher expression of transporters, especially under flow. TERT1-parent, -OAT1, and -OAT3 cells formed robust barriers but were unaffected by flow. TERT1-OAT1 cells exhibited inhibitable para-aminohippurate transport that was enhanced by flow. However, efficient tenofovir secretion and perfluorooctanoic acid reabsorption by TERT1-OAT1 cells were not modulated by flow. Gene expression showed that TERT1 and TERT1-OAT1 cells were more correlated with human kidney than other cell lines but that flow did not have noticeable effects. Overall, our data show that addition of flow to in vitro studies of the renal proximal tubule may afford benefits in some aspects of modeling kidney function but that careful consideration of the impact such adaptations would have on the cost and throughput of the experiments is needed. SIGNIFICANCE STATEMENT: The topic of reproducibility and robustness of complex microphysiological systems is looming large in the field of biomedical research; therefore, uptake of these new models by the end-users is slow. This study systematically compared various renal proximal tubule epithelial cell sources and experimental conditions, aiming to identify the level of model complexity needed for testing renal tubule transport. We demonstrate that although tissue chips may afford some benefits, their throughput and complexity need careful consideration in each context of use.
This study aims at generating highly aligned functional myotubes using graphene as the underlying scaffold. Graphene not only supports the growth of C2C12 muscle cells but also enhances its differentiation and leads to spontaneous patterning of myotubes.
