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

Aug 22, 2026

Mitochondrial dysfunction is implicated across metabolic disorders and mitochondrial diseases, and mitochondrial DNA (mtDNA) transfer is emerging as a route to restore mitochondrial activity in damaged cells. This study establishes an ex vivo expansion strategy for mouse hematopoietic stem cells (HSCs) and evaluates functional mitochondrial transfer after transplantation. Expanded donor cells engraft effectively in irradiated recipients. Using mitochondrial-nuclear exchange (MNX) mice, donor HSCs were shown to deliver mtDNA to host cells, supporting mitochondrial transfer in a transplant context.

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CategoryResearch & Report

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Reading Time40 min

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cells Article Mitochondrial Transfer to Host Cells from Ex Vivo Expanded Donor Hematopoietic Stem Cells Hiroki Kawano 1,2, Yuko Kawano 2,3, Chen Yu 4, Mark W. LaMere 1,2, Matthew J. McArthur 4, Michael W. Becker 1,2, Scott W. Ballinger 5, Satoshi Gojo 6, Roman A. Eliseev 4, * and Laura M. Calvi 2,3, * Citation: Kawano, H.; Kawano, Y.; Yu, C.; LaMere, M.W.; McArthur, M.J.; Becker, M.W.; Ballinger, S.W.; Gojo, S.; Eliseev, R.A.; Calvi, L.M. Mitochondrial Transfer to Host Cells from Ex Vivo Expanded Donor Hematopoietic Stem Cells. Cells 2023, 12, 1473. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12111473 Academic Editor: Nickolay Brustovetsky Received: 17 April 2023 Revised: 21 May 2023 Accepted: 23 May 2023 Published: 25 May 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Division of Hematology/Oncology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA 2 James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA 3 Division of Endocrinology and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA 4 Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA 5 Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA 6 Department of Regenerative Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan * Correspondence: [roman_eliseev@urmc.rochester.edu](roman_eliseev@urmc.rochester.edu) (R.A.E.); [laura_calvi@urmc.rochester.edu](laura_calvi@urmc.rochester.edu) (L.M.C.); Tel.: +1-585-276-3396 (R.A.E.); +1-585-275-4099 (L.M.C.) Abstract: Mitochondrial dysfunction is observed in various conditions, from metabolic syndromesto 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. Keywords: mitochondrial DNA 2; ex vivo HSC expansion 3; MNX mouse, 5; in vivo mitochondrial transfer 1. Introduction Mitochondria are highly dynamic organelles that regulate cell bioenergetics and ﬂuxes of key metabolites and ions [1] . Their diverse functions are regulated by ﬁssion and fusion machinery, factors controlling biogenesis, ion transport, quality control mechanisms such as autophagy/mitophagy, and other factors [2] . Mitochondrial impairment has been shown to play a role in vari

FAQs

What is the main objective of the study?

To develop an ex vivo approach that expands donor hematopoietic stem cells and to test whether donor HSCs can transfer mitochondrial DNA to host cells after transplantation.

How were donor hematopoietic stem cells prepared for transplantation?

Mouse HSCs were expanded ex vivo in culture to obtain sufficiently effective donor engraftment following transplantation.

What model was used to track mitochondrial transfer from donor to host?

Mitochondrial-nuclear exchange (MNX) mice were used, combining C57BL/6J nuclei with C3H/HeN mitochondria, enabling identification of mitochondrial DNA transfer.

Aug 22, 2026

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