Toward Immunocompetent 3D Skin Models

Abstract

3D human skin models provide a platform for toxicity testing, biomaterials evaluation, and investigation of fundamental biological processes. However, the majority of current in vitro models lack an inflammatory system, vasculature, and other characteristics of native skin, indicating scope for more physiologically complex models. Looking at the immune system, there are a variety of cells that could be integrated to create novel skin models, but to do this effectively it is also necessary to understand the interface between skin biology and tissue engineering as well as the different roles the immune system plays in specific health and disease states. Here, a progress report on skin immunity and current immunocompetent skin models with a focus on construction methods is presented; scaffold and cell choice as well as the requirements of physiologically relevant models are elaborated. The wide range of technological and fundamental challenges that need to be addressed to successfully generate immunocompetent skin models and the steps currently being made globally by researchers as they develop new models are explored. Induced pluripotent stem cells, microfluidic platforms to control the model environment, and new real-time monitoring techniques capable of probing biochemical processes within the models are discussed.

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

“…Considering the limitations of the monolayer systems, the employment of more complex and stratified models is expected to provide further information on the effect and the role of key cytokines on the pathogenesis and thereby, on the pathology of psoriasis itself [ 119 ]. Indeed, although monolayer psoriatic models are very useful to study deregulated genes associated with pathological keratinocytes, this type of model does not provide a transcriptomic profile that highlights all the different interactions existing between the different components of psoriatic skin, hence the interest in 3D models for transcriptomic studies.…”

Human Skin Equivalents Demonstrate Need for Neuro‐Immuno‐Cutaneous System

“…In the current study, exchanging hASCs for lipoaspirate alters the tissue model and may be better suited to study obesity, for example, because the entire adipose tissue is exploited, including the immune component. The silk scaffold with lipoaspirate was used as a patient‐specific model . The main advantage of using lipoaspirate, as opposed to a single‐cell source such as hASCs, is that numerous primary, human cell types are contributed from the lipoaspirate (adipocytes, preadipocytes, endothelial cells, and smooth muscle cells, immune cells including macrophages) which results in a more physiologically relevant system than a stem‐cell‐only model .…”

“…The main advantage of using lipoaspirate, as opposed to a single‐cell source such as hASCs, is that numerous primary, human cell types are contributed from the lipoaspirate (adipocytes, preadipocytes, endothelial cells, and smooth muscle cells, immune cells including macrophages) which results in a more physiologically relevant system than a stem‐cell‐only model . However, the disadvantages include patient variability and variability in cell‐type composition which may differ from patient‐to‐patient, or even in different samples from the same patient source …”

“…There is interest in the neurological and immune components in skin, but most studies only focus on one system at a time, not both . The in vitro HSE system described herein is a multilayered, full thickness skin model, containing only primary human cells, including human induced neural stem cells (hiNSCs), and tissue‐inherent immune cells from lipoaspirate utilized in the hypodermis .…”

Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways

“…Indeed, models based on primary human cells are currently believed to more accurately reflect in vivo responses towards selected compounds, even though their applicability is partially restricted by limited life span and the necessity for cell isolation prior to experiment [ 1 , 5 ]. In addition to the usage of primary cells, significant advances have also been achieved in the field of tissue engineering, a promising approach in approximating in vitro results to observed in vivo responses [ 6 , 7 , 8 , 9 ]. Current research sets a special focus on primitive cell types (e.g., embryonal stem cells, induced pluripotent cells), as these are appreciated to be particularly vulnerable towards exogenous stimuli and also display a model for developmental toxicity testing [ 10 , 11 , 12 , 13 ].…”