Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

Abstract

Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation.

Towards an In Vitro 3D Model for Photosynthetic Cancer Treatment: A Study of Microalgae and Tumor Cell Interactions

“…It is recognized as the go-to microorganism model for studying photosynthesis as it is easy to culture and has an extensive array of molecular tools available [ 36 ]. Moreover, it does not produce exotoxins or infectious agents [ 37 ], which has propelled its use as a nutritional supplement and its application in several biomedical approaches [ 28 , 29 , 35 ]. On the other hand, human melanomas were chosen as the cellular model because they tend to develop acidic and hypoxic areas [ 38 ] that lead to increased tumor malignancy [ 39 ] and high resistance to conventional ROS induction and drug treatments [ 40 ].…”

“…By using photosynthetic microorganisms, such as microalgae and cyanobacteria, researchers have explored the induction of photosynthesis as a simple and controllable local source of oxygen for tissues. This approach has been evaluated in various in vitro and in vivo hypoxic models, such as wound healing [ 24 ], myocardial ischemia [ 25 ], 3D bioprinted constructs [ 26 , 27 ], and ex situ kidney preservation [ 28 ]. Moreover, a phase I clinical trial using photosynthetic collagen scaffolds with the microalgae Chlamydomonas reinhardtii was recently published [ 29 ], showing the safety of such photosynthetic approaches in humans.…”

Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

“…The first results show an adequate and non‐harmful O 2 production. This could represent a novel and promising strategy for delivering oxygen in organ preservation 41 …”

New trends in biotechnological applications of photosynthetic microorganisms

“…Organ damage and failure represent a crucial health care problem and are among the leading causes of clinical patient deaths globally (Home -GODT, 2019). One of the major challenges in engineered tissues, including brain, cardiac, skin, muscle, or pancreas, is the sustained supply of oxygen and nutrients to prevent critical hypoxia of tissue-engineered constructs during cultivation (Suvarnapathaki et al, 2019;Zhong et al, 2021a), which is called oxygenation (Veloso-Giménez et al, 2021). To resolve the aforementioned issues, recent research has been exploring the development of a new class of multifunctional "breathing" biomaterials that will provide adequate oxygen and vascularization of immobilized cells.…”