Microalgae share key features with human erythrocytes and can safely circulate through the vascular system in mice.

As animal cells cannot produce oxygen, erythrocytes are responsible for gas interchange, being able to capture and deliver oxygen upon tissue request. Interestingly, several other cells in nature produce oxygen by photosynthesis, raising the question of whether they could circulate within the vascular networks, acting as an alternative source for oxygen delivery. To address this long-term goal, here some physical and mechanical features of the photosynthetic microalga Chlamydomona reinhardtii were studied and compared with erythrocytes, revealing that both exhibit similar size and rheological properties. Moreover, key biocompatibility aspects of the microalgae were evaluated in vitro and in vivo, showing that C. reinhardtii can be co-cultured with endothelial cells, without affecting each other's morphology and viability. Moreover, short-term systemic perfusion of the microalgae showed a thoroughly intravascular distribution in mice. Finally, the systemic injection of high numbers of microalgae did not trigger deleterious responses in living mice. Altogether, this work provides key scientific insights to support the notion that photosynthetic oxygenation could be achieved by circulating microalgae, representing another important step towards human photosynthesis. KEY POINTS: • C. reinhardtii and endothelial cells are biocompatible in vitro. • C. reinhardtii distribute throughout the entire vasculature after mice perfusion. • C. reinhardtii do not trigger deleterious responses after injection in mice.

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

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.

The increase in body weight induced by lack of methyl CpG binding protein-2 is associated with altered leptin signalling in the hypothalamus.

Methyl CpG binding protein-2 (MECP2) is a chromatin-remodelling factor with a dual role in gene expression. Evidence from patients carrying MECP2 mutations and from transgenic mouse models demonstrates that this protein is involved in the control of body weight. However, the mechanism for this has not been fully elucidated. To address this, we used a previously characterized Mecp2-null mouse model and found that the increase in body weight is associated with an increased amount of adipose tissue and high leptin levels. Appropriate body weight control requires the proper expression of pro-opiomelanocortin (Pomc) and agouti-related peptide (Agrp), two neuropeptides essential for satiety and appetite signals, respectively. Our results show that in the absence of Mecp2, Pomc and Agrp mRNA expression are altered, and the mice are leptin resistant. To determine the mechanism underlying the defective leptin sensing, we evaluated the expression of genes and the post-translational modifications associated with leptin signalling, which are fundamental to Pomc and Agrp transcriptional control and proper leptin response. We found a decrease in the phosphorylation level of Akt and its target protein Foxo1, which indicate an alteration in leptin-induced signal transduction. Our results demonstrate that the absence of Mecp2 disrupted body weight balance by altering post-translational modifications in leptin-signalling components that regulate Pomc and Agrp expression.