Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells

Abstract

Mitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain 5 tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses acrossPBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach 10

Tools and approaches for analyzing the role of mitochondria in health, development and disease using human cerebral organoids

“…Confocal and two-photon imaging were used to demonstrate that the organoids exhibit progressive differentiation, robust integration, and survival within the host (Mansour et al, 2018). Two years later, Doung et al reported the first attempt at systematically tracking mitochondrial health, including their morphology, during the different stages of development in cerebral organoids cut in 100 μm slices and labeled with JC-1 (Duong et al, 2020). However, both CLSM and two-photon microscopy have several limitations when dealing with long-term live imaging experiments.…”