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Review
. 2018;205(5-6):350-371.
doi: 10.1159/000493162. Epub 2018 Oct 1.

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Shahrzad Fathollahipour  1 , Pritam S Patil  1 , Nic D Leipzig  2
Affiliations
Review

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Shahrzad Fathollahipour et al. Cells Tissues Organs. 2018.

Abstract

Oxygen is a vital source of energy necessary to sustain and complete embryonic development. Not only is oxygen the driving force for many cellular functions and metabolism, but it is also involved in regulating stem cell fate, morphogenesis, and organogenesis. Low oxygen levels are the naturally preferred microenvironment for most processes during early development and mainly drive proliferation. Later on, more oxygen and also nutrients are needed for organogenesis and morphogenesis. Therefore, it is critical to maintain oxygen levels within a narrow range as required during development. Modulating oxygen tensions is performed via oxygen homeostasis mainly through the function of hypoxia-inducible factors. Through the function of these factors, oxygen levels are sensed and regulated in different tissues, starting from their embryonic state to adult development. To be able to mimic this process in a tissue engineering setting, it is important to understand the role and levels of oxygen in each developmental stage, from embryonic stem cell differentiation to organogenesis and morphogenesis. Taking lessons from native tissue microenvironments, researchers have explored approaches to control oxygen tensions such as hemoglobin-based, perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic tissue engineering scaffolds and organoids, with the aim of overcoming insufficient or nonuniform oxygen levels and nutrient supply.

Keywords: Embryonic development; Hypoxia; Morphogenesis; Organoids; Oxygen bioavailability; Oxygen delivery; Tissue engineering.

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Conflict of interest statement

Disclosure Statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
(A) Oxygen levels in different embryonic development stages. (B) Measures of in vivo O2 levels in different tissues ([Fitzgerald et al., 1999; Simon and Keith, 2008; Mohyeldin et al., 2010; Wang and Zhao, 2010; Abdollahi et al., 2011; Carreau et al., 2011; Ortega et al., 2017]).
Fig. 2.
Fig. 2.
Oxygen levels in the adult mammal.
Fig. 3.
Fig. 3.
(A) Oxygen levels depend on the distance from the primary blood flow and are location-specific in a vascularized tissue engineering scaffold. (B) Different oxygen carrier strategies shown encapsulated in tissue engineering scaffolds creates a more uniform oxygen gradient (Figure modified from [papStoppel and Roberts, 2012]).
Fig. 4.
Fig. 4.
The overall development and application of organoids emphasizing the issue of inhomogeneous oxygen delivery throughout the developing spheroid.
See this image and copyright information in PMC

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