Mitochondrial augmentation of CD34
Journal
NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846
Informations de publication
Date de publication:
24 Sep 2021
24 Sep 2021
Historique:
received:
18
02
2021
accepted:
19
08
2021
entrez:
25
9
2021
pubmed:
26
9
2021
medline:
26
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34561447
doi: 10.1038/s41536-021-00167-7
pii: 10.1038/s41536-021-00167-7
pmc: PMC8463667
doi:
Types de publication
Journal Article
Langues
eng
Pagination
58Informations de copyright
© 2021. The Author(s).
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