Oocytes, embryos and pluripotent stem cells from a biomedical perspective.

Poul Hyttel,Laís Vicari De Figueiredo Pessôa,Remmy John Assey,Torben Greve,Lotte Björg Stroebech,Trudee Fair,Kristine Freude,Katarina Stoklund Dittlau,Jozef Laurincik,Jan Bojsen-Møller Secher,Vanessa J Hall,Henrik Callesen

doi:10.21451/1984-3143-ar2019-0054

Abstract

The veterinary and animal science professions are rapidly developing and their inherent and historical connection to agriculture is challenged by more biomedical and medical directions of research. While some consider this development as a risk of losing identity, it may also be seen as an opportunity for developing further and more sophisticated competences that may ultimately feed back to veterinary and animal science in a synergistic way. The present review describes how agriculture-related studies on bovine in vitro embryo production through studies of putative bovine and porcine embryonic stem cells led the way to more sophisticated studies of human induced pluripotent stem cells (iPSCs) using e.g. gene editing for modeling of neurodegeneration in man. However, instead of being a blind diversion from veterinary and animal science into medicine, these advanced studies of human iPSC-derived neurons build a set of competences that allowed us, in a more competent way, to focus on novel aspects of more veterinary and agricultural relevance in the form of porcine and canine iPSCs. These types of animal stem cells are of biomedical importance for modeling of iPSC-based therapy in man, but in particular the canine iPSCs are also important for understanding and modeling canine diseases, as e.g. canine cognitive dysfunction, for the benefit and therapy of dogs.

Highlights

The veterinary and animal science professions are rapidly developing in a shifting scientific environment
Through our struggles towards establishing bovine and porcine embryonic stem cells (ESCs), we developed a skill set that allowed us to embark on human induced pluripotent stem cells (iPSCs) and the use of these fascinating cells for modelling neurodegeneration
Based on the use of patient iPSC-derived neurons and their isogenic controls, we have clearly demonstrated specific disease phenotypes in the Frontotemporal dementia linked to chromosome 3 (FTD3) neurons, all of which can be rescued by correction of the disease-causing mutation

Summary

Introduction

The veterinary and animal science professions are rapidly developing in a shifting scientific environment. The competences gained by our studies of oocyte maturation, fertilization and initial embryonic development in cattle allowed us to move into the stem cell area for creating novel potentials in agriculture and biomedicine. Based on the use of patient iPSC-derived neurons and their isogenic controls, we have clearly demonstrated specific disease phenotypes in the FTD3 neurons, all of which can be rescued by correction of the disease-causing mutation These include misregulated expression of genes related to endosomes, mitochondria and iron homeostasis, which was verified by immunocytochemistry, electron microscopy and cellular assays demonstrating large neuronal accumulations of endosomes, lack of mitochondrial axonal distribution and cristae formation, reduction in mitochondrial respiration capacity and intracellular iron accumulation (Zhang et al, 2017). It has been a great privilege to encompass a full circle of scientific progress from bovine oocytes and embryos through bovine and porcine stem cells into human stem cell-based disease modeling and back to animal stem cells and, practical implementation of bovine oocyte and embryo technologies

Conclusions

Findings

Acknowledgments and Funding disclosure statement