TY - JOUR T1 - Breathing in vitro: Designs and applications of engineered lung models JF - Journal of Tissue Engineering Y1 - 2021 A1 - Nossa, Roberta A1 - Costa, Joana A1 - Cacopardo, Ludovica A1 - Ahluwalia, Arti KW - aerosol exposure KW - fluidic systems KW - in vitro models KW - Lung models KW - stretching systems AB -

The aim of this review is to provide a systematic design guideline to users, particularly engineers interested in developing and deploying lung models, and biologists seeking to identify a suitable platform for conducting in vitro experiments involving pulmonary cells or tissues. We first discuss the state of the art on lung in vitro models, describing the most simplistic and traditional ones. Then, we analyze in further detail the more complex dynamic engineered systems that either provide mechanical cues, or allow for more predictive exposure studies, or in some cases even both. This is followed by a dedicated section on microchips of the lung. Lastly, we present a critical discussion of the different characteristics of each type of system and the criteria which may help researchers select the most appropriate technology according to their specific requirements. Readers are encouraged to refer to the tables accompanying the different sections where comprehensive and quantitative information on the operating parameters and performance of the different systems reported in the literature is provided.

VL - 12 ER - TY - JOUR T1 - Scaling of joint mass and metabolism fluctuations in in silico cell-laden spheroids JF - Proceedings of the National Academy of Sciences Y1 - 2021 A1 - Botte, Ermes A1 - Biagini, Francesco A1 - Magliaro, Chiara A1 - Rinaldo, Andrea A1 - Maritan, Amos A1 - Ahluwalia, Arti AB -

Variations and fluctuations are characteristic features of biological systems and are also manifested in cell cultures. Here, we describe a computational pipeline for identifying the range of three-dimensional (3D) cell-aggregate sizes in which nonisometric scaling emerges in the presence of joint mass and metabolic rate fluctuations. The 3D cell-laden spheroids with size and single-cell metabolic rates described by probability density functions were randomly generated in silico. The distributions of the resulting metabolic rates of the spheroids were computed by modeling oxygen diffusion and reaction. Then, a method for estimating scaling exponents of correlated variables through statistically significant data collapse of joint probability distributions was developed. The method was used to identify a physiologically relevant range of spheroid sizes, where both nonisometric scaling and a minimum oxygen concentration (0.04 mol⋅m−3) is maintained. The in silico pipeline described enables the prediction of the number of experiments needed for an acceptable collapse and, thus, a consistent estimate of scaling parameters. Using the pipeline, we also show that scaling exponents may be significantly different in the presence of joint mass and metabolic-rate variations typically found in cells. Our study highlights the importance of incorporating fluctuations and variability in size and metabolic rates when estimating scaling exponents. It also suggests the need for taking into account their covariations for better understanding and interpreting experimental observations both in vitro and in vivo and brings insights for the design of more predictive and physiologically relevant in vitro models.

VL - 118 UR - https://www.pnas.org/content/118/38/e2025211118 ER - TY - JOUR T1 - Tools and approaches for analysing the role of mitochondria in health, development and disease using human cerebral organoids JF - Developmental Neurobiology Y1 - 2021 A1 - Liput, Michał A1 - Magliaro, Chiara A1 - Kuczyńska, Zuzanna A1 - Zayat, Valery A1 - Ahluwalia, Arti A1 - Buzanska, Leonora KW - cerebral organoids; computational models; mitochondria imaging; mitochondrial dyes; reporter fluorescent proteins. AB -

Mitochondria are cellular organelles involved in generating energy to power various processes in the cell. Although the pivotal role of mitochondria in neurogenesis was demonstrated (first in animal models), very little is known about their role in human embryonic neurodevelopment and its pathology. In this respect human-induced pluripotent stem cells (hiPSC)-derived cerebral organoids provide a tractable, alternative model system of the early neural development and disease that is responsive to pharmacological and genetic manipulations, not possible to apply in humans. Although the involvement of mitochondria in the pathogenesis and progression of neurodegenerative diseases and brain dysfunction has been demonstrated, the precise role they play in cell life and death remains unknown, compromising the development of new mitochondria-targeted approaches to treat human diseases. The cerebral organoid model of neurogenesis and disease in vitro provides an unprecedented opportunity to answer some of the most fundamental questions about mitochondrial function in early human neurodevelopment and neural pathology. Largely an unexplored territory due to the lack of tools and approaches, this review focuses on recent technological advancements in fluorescent and molecular tools, imaging systems, and computational approaches for quantitative and qualitative analyses of mitochondrial structure and function in three-dimensional cellular assemblies-cerebral organoids. Future developments in this direction will further facilitate our understanding of the important role or mitochondrial dynamics and energy requirements during early embryonic development. This in turn will provide a further understanding of how dysfunctional mitochondria contribute to disease processes.

UR - https://pubmed.ncbi.nlm.nih.gov/33725382/ ER -