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 therapeut...
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Nature Portfolio
2021
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oai:doaj.org-article:07e67ce070a84572b832c40c4b1c99f02021-12-02T11:35:41ZCharacterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells10.1038/s41598-021-84071-62045-2322https://doaj.org/article/07e67ce070a84572b832c40c4b1c99f02021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84071-6https://doaj.org/toc/2045-2322Abstract 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 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 across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.Angela DuongAlesya EvstratovaAdam SivitilliJ. Javier HernandezJessica GosioAzizia WahediNeal SondheimerJeff L. WranaJean-Martin BeaulieuLiliana AttisanoAna C. AndreazzaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
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Medicine R Science Q Angela Duong Alesya Evstratova Adam Sivitilli J. Javier Hernandez Jessica Gosio Azizia Wahedi Neal Sondheimer Jeff L. Wrana Jean-Martin Beaulieu Liliana Attisano Ana C. Andreazza Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
description |
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 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 across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples. |
format |
article |
author |
Angela Duong Alesya Evstratova Adam Sivitilli J. Javier Hernandez Jessica Gosio Azizia Wahedi Neal Sondheimer Jeff L. Wrana Jean-Martin Beaulieu Liliana Attisano Ana C. Andreazza |
author_facet |
Angela Duong Alesya Evstratova Adam Sivitilli J. Javier Hernandez Jessica Gosio Azizia Wahedi Neal Sondheimer Jeff L. Wrana Jean-Martin Beaulieu Liliana Attisano Ana C. Andreazza |
author_sort |
Angela Duong |
title |
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
title_short |
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
title_full |
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
title_fullStr |
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
title_full_unstemmed |
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
title_sort |
characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/07e67ce070a84572b832c40c4b1c99f0 |
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