A Computational Model of Cellular Engraftment on Lung Scaffolds

Abstract

The possibility that stem cells might be used to regenerate tissue is now being investigated for a variety of organs, but these investigations are still essentially exploratory and have few predictive tools available to guide experimentation. We propose, in this study, that the field of lung tissue regeneration might be better served by predictive tools that treat stem cells as agents that obey certain rules of behavior governed by both their phenotype and their environment. Sufficient knowledge of these rules of behavior would then, in principle, allow lung tissue development to be simulated computationally. Toward this end, we developed a simple agent-based computational model to simulate geographic patterns of cells seeded onto a lung scaffold. Comparison of the simulated patterns to those observed experimentally supports the hypothesis that mesenchymal stem cells proliferate preferentially toward the scaffold boundary, whereas alveolar epithelial cells do not. This demonstrates that a computational model of this type has the potential to assist in the discovery of rules of cellular behavior.

Bioprintable Lung Extracellular Matrix Hydrogel Scaffolds for 3D Culture of Mesenchymal Stromal Cells

“…In the case of lung diseases, although the main hypothesis is that most benefits induced by the use of MSCs for treatment come from their paracrine effect, the determination of the technical issues related to cell culture previous to administration is still an open issue [ 10 ]. Accordingly, a considerable effort is now currently devoted to precondition the MSCs by optimizing culture conditions to improve their therapeutic potential before infusion [ 11 , 12 ]. Most strategies for pre-conditioning MSCs involve the use of routine tissue culture in which different cytokines, growth factors, hormones [ 13 ], or pharmacological agents [ 14 ] are supplemented to the cells.…”

The Potential Contribution of Biopolymeric Particles in Lung Tissue Regeneration of COVID-19 Patients

“…Mesenchymal stem cells preferentially developed toward the scaffold border, while alveolar epithelial cells did not. This highlights the significance of computational models in understanding cellular activity [122]. In addition, the cell responses to gemcitabine therapy were equivalent to those reported in clinical trials for lung carcinoma, showing that they may help design anticancer treatments by offering more accurate preclinical predictions [123].…”

What is the need and why is it time for innovative models for understanding lung repair and regeneration?

“…In parallel with imaging, increasing advances in “omics” technologies, including in situ genomics and proteomics, along with advances in machine learning, single cell RNA sequencing and development of multi-omics atlases including gene and protein lung maps, are all tools that will help advance lung regenerative medicine and engineering ( Pothen et al, 2016 ; Jorba et al, 2019 ; Marklein et al, 2019 ; Andreu et al, 2021 ).…”