外周血单核细胞作为周围神经损伤修复中线粒体移植治疗的新型来源

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Published: 14 October 2026

Haihao Gao¹^na1,
Zhe Wang^1,2,3^na1,
Yuhui Cui^1,2^na1,
Haofeng Cheng¹ &
…
Jianning Zhang ORCID: orcid.org/0009-0003-2796-5451¹

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Abstract

Peripheral nerve injury remains a significant clinical challenge, with energy metabolism disorders severely hampering complete nerve regeneration. While mitochondrial transplantation has emerged as a promising therapeutic approach to restore cellular bioenergetics and promote neural repair, current mitochondrial sources from mesenchymal stem cells or skeletal muscles require invasive harvesting procedures. This study investigated peripheral blood mononuclear cells as a novel, minimally invasive source for therapeutic mitochondria in peripheral nerve regeneration. Functional mitochondria were isolated from both rat and human peripheral blood mononuclear cells and adipose-derived stem cells using standardized protocols. Mitochondrial structure and function were evaluated through transmission electron microscopy, proteomic analysis, and ATP production assays. Therapeutic efficacy was assessed in both a rat sciatic nerve crush injury model and a 10-mm segmental sciatic nerve defect model bridged with an acellular nerve allograft (ANA). Functional recovery was evaluated by histological, electrophysiological, muscular, and gait analyses. In vitro studies further examined mitochondrial internalization and bioenergetic effects in neuronal cells, while transcriptomic analysis of dorsal root ganglion neurons were performed to explore potential mechanisms underlying mitochondrial-enhanced axonal growth. Successfully isolated peripheral blood mononuclear cell-derived mitochondria demonstrated intact ultrastructure and shared similar protein profiles with adipose-derived stem cell mitochondria, particularly in oxidative phosphorylation pathways. In the sciatic nerve crush model, sub-epineural injection of peripheral blood mononuclear cell-derived mitochondria significantly improved functional recovery at 21 days post-injury, with enhanced axonal regeneration and reduced muscle atrophy comparable to adipose-derived stem cell mitochondria. In the 10-mm nerve defect model, PBMC-derived mitochondria loaded into ANAs improved CMAP recovery, axonal regeneration, Schwann cell-associated nerve reconstruction, target muscle preservation, and gait function at 12 weeks postoperatively. Human-derived mitochondria did not produce an evident systemic inflammatory response or major-organ injury under the conditions examined. In vitro studies showed effective mitochondrial internalization within 3 h, significantly enhancing cellular respiratory capacity. Mitochondrial transplantation promoted axon growth in dorsal root ganglia neurons, with transcriptomic analysis implicating axon-guidance-related pathways. PBMCs represent a readily accessible and minimally invasive source of mitochondria for transplantation therapy. PBMC-derived mitochondria achieved regenerative efficacy comparable to conventional ADSC-derived mitochondria in both crush and segmental nerve defect models, while avoiding the need for additional tissue harvesting and prolonged cell expansion. These findings support the further development of autologous PBMC-derived mitochondrial transplantation as a potential strategy for peripheral nerve repair.

Abbreviations

PBMCs:: Peripheral blood mononuclear cells
ADSCs:: Adipose-derived stem cells
NIH:: National Institutes of Health
FBS:: Fetal bovine serum
TEM:: Transmission electron microscope
TOMM20:: Mitochondrial membrane complex subunit 20
DTT:: Dithiothreitol
ABC:: Ammonium bicarbonate
DIA:: Data-independent acquisition
FA:: Formic acid
DEPs:: Differentially expressed proteins
COG:: clusters of orthologous groups
KEGG:: Kyoto Encyclopedia of Genes and Genomes
SFI:: Sciatic Functional Index
DAPI:: 4’,6-diamidino-2-phenylindole
ANA:: Acellular nerve allograft
SD:: Sprague–Dawley
CMAPs:: Compound muscle action potentials
MOI:: Multiplicity of infection
FCCP:: Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone
Rot/AA:: Rotenone/Antimycin A
CMST:: Cell Mito Stress Test
DRG:: Dorsal root ganglion
RIN:: RNA integrity number
DEGs:: differentially expressed genes
GO:: Gene Ontology
GSEA:: Gene set enrichment analysis
SEM:: Standard error of the mean
CCK-8:: Cell Counting Kit-8
NF-200:: Neurofilament-200
OCR:: Oxygen consumption rate
MF:: Molecular Function
CC:: Cellular Component
BP:: Biological Process
P5CS:: Pyrroline-5-carboxylate synthase
NTFs:: Neurotrophic factors
MOM:: Mitochondrial outer membrane

Funding

This study was supported by Open Project of Chongqing Engineering Research Center of Organ Intelligent Bio-Manufacturing (CQERC-OIBM20241001).

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Author notes

Haihao Gao, Zhe Wang and Yuhui Cui contributed equally to this work.

Authors and Affiliations

Department of Neurosurgery, 1st Medical Center of PLA General Hospital, Beijing, 100853, China
Haihao Gao, Zhe Wang, Yuhui Cui, Haofeng Cheng & Jianning Zhang
Chinese PLA Medical School, Beijing, 100853, China
Zhe Wang & Yuhui Cui
Department of Neurosurgery, Hainan Hospital of PLA General Hospital, Sanya, 572013, Hainan Province, China
Zhe Wang

Authors

Haihao Gao
Zhe Wang
Yuhui Cui
Haofeng Cheng
Jianning Zhang

Corresponding author

Correspondence to Jianning Zhang.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The Administration Committee of Experimental Ethics, the Chinese PLA General Hospital approved the use of animals in this study (approval No. 2023-X19-79) and usage of human sample (Approval No. 2023KY088-KS001). We confirmed that all methods were carried out in accordance with relevant guidelines and regulations and approved by the Chinese PLA General Hospital. Informed consents were obtained from all volunteers who donated the peripheral blood.

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No individual person’s data were obtained or used in this study.

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Gao, H., Wang, Z., Cui, Y. et al. Peripheral blood mononuclear cells as a novel source for mitochondrial transplantation therapy in peripheral nerve injury repair. Sci Rep (2026). https://doi.org/10.1038/s41598-026-73623-3

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Received: 14 October 2025
Accepted: 24 September 2026
Published: 14 October 2026
DOI: https://doi.org/10.1038/s41598-026-73623-3