In Vitro Models for Studying Transport Across Epithelial Tissue Barriers

Abstract

Epithelial barriers are the body's natural defense system to regulating passage from one domain to another. In our efforts to understand what can and cannot cross these barriers, models have emerged as a reductionist approach to rigorously study and investigate this question. In particular, in vitro tissue models have become prominent as there is an increased exploration of understanding biological molecular transport. Herein, we introduce the pertinent physiology, then discuss recent studies and approaches for building models of five epithelial tissues: skin, the gastrointestinal tract, the lungs, the blood-brain barrier, and the placenta. In particular, we evaluated literature from the past 5 years utilizing a tissue model to evaluate molecular transport. We then compare physiology of these tissues and discuss similarities in approaches, across tissues, to validate these models. We conclude with a summary of the approaches of growing interest across multiple tissues and an outlook on future steps to improve these models.

Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

“…Some investigations have shown that oncogene-transfected hBMECs operate as same as primary cells. As transfected hBMECs have shown good barrier tightness and paracellular permeability, these cell lines are considered promising for establishing an in vitro BBB model ( Arumugasaamy et al, 2019 ). Brain endothelial cells derived from iPSCs (induced pluripotent stem cells) and hematopoietic stem cells are also used to develop BBB models ( Appelt-Menzel et al, 2017 ).…”

“…Microfluidic BBB models will soon replace animal testing to be employed in scientific and clinical research. Advanced microfluidics may represent the future of BBB models due to their design flexibility, capacity to combine coculture methods, and compliance ( Arumugasaamy et al, 2019 ). In addition, novel modeling techniques based on the culture of brain spheroids and organoids were established a few years earlier.…”

The Characteristic Recovery Time as a Novel, Noninvasive Metric for Assessing In Vivo Cartilage Mechanical Function

“…Moreover, quantitative MRI (qMRI) techniques have emerged as methods that reflect cartilage composition and health. 11 , 30 , 31 Specifically, qMRI measures such as T1rho and T2 relaxation times are sensitive to changes in proteoglycan concentration, collagen content and organization, and water content, 11 , 18 , 30 , 45 and can be obtained noninvasively. Studies have also shown that these qMRI measures change during OA progression, 20 , 28 – 31 , 35 motivating their use as indicators of cartilage health.…”

Dual‐chambered membrane bioreactor for coculture of stratified cell populations

“…Skin is composed of multiple stratified layers that act as a protective barrier against external mechanical and biochemical factors (Arumugasaamy, Navarro, Kent Leach, Kim, & Fisher, ; Zhang & Michniak‐Kohn, ). Mammalian skin layers include the epidermis, dermis, and hypodermis.…”

“…The interactions between layers allow for skin to be an efficient barrier and any damage to it causes immediate compromised thermoregulation, fluid shifts, and risk of sepsis (Arumugasaamy et al, ; Markeson et al, ; Peck, Molnar, & Swart, ). Also, blood vessels and nerves grow along the interfaces of these layers forming the vascular plexuses; a lack of synergistic development of the layers results in deficient vascularization and innervation which impairs skin function (Kolarsick et al, ; Markeson et al, ; McLafferty et al, ; Wong et al, ).…”