Table 3.

Mitochondrial transplantation effect to prevent drug-related toxicity.

Author/Year	Model/Disease	Mitochondria source	Transfer parameters	Clinical & biological evidences	Mitochondrial mechanisms modulation
Jin 2024 [90]	C57BL/6N mice Doxorubicin cardiotoxicity	MSC cells Not specified	Dose: 3 mg/kg Administration: IV Site: not specified	Restore ejection fraction and fractional shortening ↓ fibrosis ↓ apoptosis	↑ ATP level ↑ mito quantity (image) ↑ anti-ox (mRNA Sdhaf2/4) ↓ autophagy (mRNA LC3BII, p62) ↓ autophagosomes (inhibit AMPK/mTOR pathway)
Kim 2024 [91]	Sprague Dawley rat Dexamethasone related amyotrophy	UC-MSC cells Human Xenogeneic	Doses: 0.5–5 μg/limb Administration: IM Site: soleus	Positive effect with 5 μg Recover muscle mass, fiber area, desmin, myogenin ↓ lactate	Act AMPK/AKT/Foxo pathway (↑Akt, ↓ FOXO3, ↓ MuRF-1, ↓ MAFbx) ↑ OXPHOS (CI, II, IV, V activity) ↑ mito biosynthesis (PGC-1, TFAM)
Kubat 2024 [92]	Sprague Dawley rat Doxorubicin muscular toxicity	Femoris Rat Allogenic	Dose: 6.5 μg mito proteins Administration: IM Sites: 3 tibialis	No protective effect No effect on apoptosis No effect on inflammation	↑ anti-ox (succinate DH, SOD)
Maia 2023 [93]	SWISS mice Oxaliplatin neurotoxicity	Liver Mice Allogenic	Dose: 0.5 mg/kg Administration: IV Site: retro-orbital	↓ cold mechanical and sensitive alteration ↓ neuro-inflammation (TNFα, TLR4)	Not investigated
Maleki 2023 [94]	Wistar rat Doxorubicin cardiotoxicity	Liver Rat Allogenic	Dose: 8*109 mito Administration: IV Site: tail	Restore ejection fraction and fractional shortening ↓ apoptosis ↓ inflammation (TNFα, IL1β, IL6)	↑ ATP level ↓ oxidative stress markers (MDA) ↑ anti-ox (SOD, CAT, GPX, GSH)
Sun 2023 [95]	C57BL/6 mice Doxorubicin cardiotoxicity	Heart Mice Allogenic	Dose: 105 mito Administration: intraventricular Site: cardiac	↑ ejection fraction and fractional shortening ↓ apoptosis	↓ Superoxide (mitosox probe) ↑ anti-ox (SOD2, OGG1) ↑ mito function (IDH2, citrate synthase) ↑ mitogenesis (PGC1-b) ↑ fusion (Opa1) ↑ OCR/ECAR ratio Act glutamine & glutamate metabolic pathway
Zhang 2023 [96]	C57BL/6 mice Doxorubicin cardiotoxicity	Heart Mice Allogenic	Dose: 5*104 mito Administration: intraventricular Site: cardiac	↑ ejection fraction and fractional shortening	↑ mito quantity (hs & ms mtDNA) ↓ intracellular ROS, ↑ mito ROS ↑ MMP ↑ baseline and max OCR
Alexander 2021 [97]	C57BL/6J mice Cisplatin neurotoxicity	MSC cells Human Xenogeneic	Dose: 170 μg mito proteins Administration: intra-nasal	↑ executive functioning Restore spatial/working memory Restore synaptic damage	↓ atypical mito morphology ↓ synaptosomal mito damage ↑ anti-ox (Nrf2)
Kubat 2021 [98]	Sprague Dawley rat Doxorubicin nephrotoxicity	MSC cells Rat Allogenic	Dose: 4*106 mito Administration: injection Site: below kidney capsule	↑ cellular regeneration ↓ apoptosis ↓ proteinuria	↑ anti-ox (SOD, GPX)
Ulger 2021 [99]	Sprague Dawley rat Acetaminophen hepatotoxicity	MSC cells Rat Allogenic	Dose: 8.2*106 mito Administration: injection Site: subscapular spleen	↓ histological alteration ↓ apoptosis and ALAT	↓ anti-ox (GSH)
Shi 2018 [100]	Sprague Dawley rat Acetaminophen hepatotoxicity	HepG2 cells Human Xenogeneic	Dose: 10 mg/kg (fresh or fractioned) Administration: IV Site: tail	Results obtained only for fresh mito ↓ histological alteration ↓ ALAT and ASAT	↑ ATP level, only for intact mito ↑ anti-ox (GSH), only for intact mito ↓ ROS, only for intact mito

Akt: protein kinase B, ALAT: alanine aminotransferase, AMPK: AMP-activated protein kinase, anti-ox: anti-oxidant; ASAT: aspartate aminotransferase, ATP: adenosine tri-phosphate, CAT: catalase, ECAR: extracellular acidification rate, FOXO: forkhead box O, GPX: glutathione peroxidase, GSH: Reduced glutathione, IDH2: isocitrate dehydrogenase 2, IL: interleukin, IM: intra-muscular, IV: intra-veinous, LC3: microtubule-associated protein light chain 3, mito: mitochondria, MAFbx: muscle atrophy F-box, MDA: malondialdehyde, MMP: Mitochondrial membrane potential, MSC: mesenchymal stromal cell, mTOR: mammalian target of rapamycin, MuRF-1: muscle RING finger protein 1, NRF2: nuclear factor erythroid 2, OCR: oxygen consumption rate, OGG1: 8-oxoguanine DNA glycosylase 1, OPA1: optic atrophy 1, OXPHOS: oxidative phosphorylation, PGC1b: Pparg coactivator 1-b, ROS: relative oxygen species, Sdhaf: Succinate dehydrogenase assembly factor 1, SOD: superoxide dismutase, TFAM: mitochondrial transcription factor A, TLR4: Toll-like receptor 4, TNFα: tumor necrosis factor α, UC-MSC: Umbilical-cord MSC, ↑: increase/improve, ↓: decrease.