Mitochondrial Transfer to Host Cells from Ex Vivo Expanded Donor Hematopoietic Stem Cells.

Autor: Kawano H; Division of Hematology/Oncology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.; James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Kawano Y; James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.; Division of Endocrinology and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Yu C; Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., LaMere MW; Division of Hematology/Oncology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.; James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., McArthur MJ; Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Becker MW; Division of Hematology/Oncology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.; James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Ballinger SW; Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Gojo S; Department of Regenerative Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan., Eliseev RA; Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Calvi LM; James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.; Division of Endocrinology and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 May 25; Vol. 12 (11). Date of Electronic Publication: 2023 May 25.
DOI: 10.3390/cells12111473
Abstrakt: Mitochondrial dysfunction is observed in various conditions, from metabolic syndromes to mitochondrial diseases. Moreover, mitochondrial DNA (mtDNA) transfer is an emerging mechanism that enables the restoration of mitochondrial function in damaged cells. Hence, developing a technology that facilitates the transfer of mtDNA can be a promising strategy for the treatment of these conditions. Here, we utilized an ex vivo culture of mouse hematopoietic stem cells (HSCs) and succeeded in expanding the HSCs efficiently. Upon transplantation, sufficient donor HSC engraftment was attained in-host. To assess the mitochondrial transfer via donor HSCs, we used mitochondrial-nuclear exchange (MNX) mice with nuclei from C57BL/6J and mitochondria from the C3H/HeN strain. Cells from MNX mice have C57BL/6J immunophenotype and C3H/HeN mtDNA, which is known to confer a higher stress resistance to mitochondria. Ex vivo expanded MNX HSCs were transplanted into irradiated C57BL/6J mice and the analyses were performed at six weeks post transplantation. We observed high engraftment of the donor cells in the bone marrow. We also found that HSCs from the MNX mice could transfer mtDNA to the host cells. This work highlights the utility of ex vivo expanded HSC to achieve the mitochondrial transfer from donor to host in the transplant setting.
Databáze: MEDLINE
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