Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit

Abstract Mitochondria are cellular organelles critical for numerous cellular processes and harboring their own circular mitochondrial DNA (mtDNA). Most mtDNA associated disorders (either deletions, mutations, or depletion) lead to multisystemic disease, often severe at a young age, with no disease-m...

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Autores principales:	Elad Jacoby, Moriya Ben Yakir-Blumkin, Shiri Blumenfeld-Kan, Yehuda Brody, Amilia Meir, Naomi Melamed-Book, Tina Napso, Gat Pozner, Esraa Saadi, Ayelet Shabtay-Orbach, Natalie Yivgi-Ohana, Noa Sher, Amos Toren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/ea28dd8efa07497c88f0f158a175ba5b
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spelling	oai:doaj.org-article:ea28dd8efa07497c88f0f158a175ba5b2021-12-02T17:27:13ZMitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit10.1038/s41536-021-00167-72057-3995https://doaj.org/article/ea28dd8efa07497c88f0f158a175ba5b2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00167-7https://doaj.org/toc/2057-3995Abstract Mitochondria are cellular organelles critical for numerous cellular processes and harboring their own circular mitochondrial DNA (mtDNA). Most mtDNA associated disorders (either deletions, mutations, or depletion) lead to multisystemic disease, often severe at a young age, with no disease-modifying therapies. Mitochondria have a capacity to enter eukaryotic cells and to be transported between cells. We describe a method of ex vivo augmentation of hematopoietic stem and progenitor cells (HSPCs) with normal exogenous mitochondria, termed mitochondrial augmentation therapy (MAT). Here, we show that MAT is feasible and dose dependent, and improves mitochondrial content and oxygen consumption of healthy and diseased HSPCs. Ex vivo mitochondrial augmentation of HSPCs from a patient with a mtDNA disorder leads to superior human engraftment in a non-conditioned NSGS mouse model. Using a syngeneic mouse model of accumulating mitochondrial dysfunction (Polg), we show durable engraftment in non-conditioned animals, with in vivo transfer of mitochondria to recipient hematopoietic cells. Taken together, this study supports MAT as a potential disease-modifying therapy for mtDNA disorders.Elad JacobyMoriya Ben Yakir-BlumkinShiri Blumenfeld-KanYehuda BrodyAmilia MeirNaomi Melamed-BookTina NapsoGat PoznerEsraa SaadiAyelet Shabtay-OrbachNatalie Yivgi-OhanaNoa SherAmos TorenNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Elad Jacoby Moriya Ben Yakir-Blumkin Shiri Blumenfeld-Kan Yehuda Brody Amilia Meir Naomi Melamed-Book Tina Napso Gat Pozner Esraa Saadi Ayelet Shabtay-Orbach Natalie Yivgi-Ohana Noa Sher Amos Toren Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
description	Abstract Mitochondria are cellular organelles critical for numerous cellular processes and harboring their own circular mitochondrial DNA (mtDNA). Most mtDNA associated disorders (either deletions, mutations, or depletion) lead to multisystemic disease, often severe at a young age, with no disease-modifying therapies. Mitochondria have a capacity to enter eukaryotic cells and to be transported between cells. We describe a method of ex vivo augmentation of hematopoietic stem and progenitor cells (HSPCs) with normal exogenous mitochondria, termed mitochondrial augmentation therapy (MAT). Here, we show that MAT is feasible and dose dependent, and improves mitochondrial content and oxygen consumption of healthy and diseased HSPCs. Ex vivo mitochondrial augmentation of HSPCs from a patient with a mtDNA disorder leads to superior human engraftment in a non-conditioned NSGS mouse model. Using a syngeneic mouse model of accumulating mitochondrial dysfunction (Polg), we show durable engraftment in non-conditioned animals, with in vivo transfer of mitochondria to recipient hematopoietic cells. Taken together, this study supports MAT as a potential disease-modifying therapy for mtDNA disorders.
format	article
author	Elad Jacoby Moriya Ben Yakir-Blumkin Shiri Blumenfeld-Kan Yehuda Brody Amilia Meir Naomi Melamed-Book Tina Napso Gat Pozner Esraa Saadi Ayelet Shabtay-Orbach Natalie Yivgi-Ohana Noa Sher Amos Toren
author_facet	Elad Jacoby Moriya Ben Yakir-Blumkin Shiri Blumenfeld-Kan Yehuda Brody Amilia Meir Naomi Melamed-Book Tina Napso Gat Pozner Esraa Saadi Ayelet Shabtay-Orbach Natalie Yivgi-Ohana Noa Sher Amos Toren
author_sort	Elad Jacoby
title	Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
title_short	Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
title_full	Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
title_fullStr	Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
title_full_unstemmed	Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
title_sort	mitochondrial augmentation of cd34+ cells from healthy donors and patients with mitochondrial dna disorders confers functional benefit
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ea28dd8efa07497c88f0f158a175ba5b
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Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit

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