Table 4.

Mitochondrial transplantation effect on sepsis.

Author/Year	Model/Disease	Mitochondria source	Transfer parameters	Clinical & biological evidences	Mitochondrial mechanisms modulation
Kim 2023 [101]	Sprague Dawley rat Sepsis	L6 cells Rat Allogenic	Dose: 200 μg mito proteins Administration: IV Site: tail	No clinical data reported ↑ expression of RT1-m2 and Cbln2	Not investigated
Kim 2023 [102]	Sprague Dawley rat Sepsis	L6, clone 9, UC-MSC cells Rat Allogenic	Dose: 200 μg mito proteins Administration: IV Site: tail	↑ survival rate at day 12 (40 % vs. 0 % only L6 mitochondria) ↓ creatinine and ALAT levels	Not investigated in vivo In vitro: ↑ basal & max respiration ↑ ATP production ↑ proton leak ↑ non mito oxygen consumption
Mokhtari 2023 [103]	Wistar rat Sepsis	Pectoralis major Rat Allogenic	Dose: 3*106 mito Administration: IV Site: tail	↑ survival rate at day 3 (50 % vs. 10 %) ↓ inflammation (TNFα, IL1β, IL6), LDH	↓ cellular ROS (DCFHDA) ↑ mito biogenesis (SIRT1, PCG-1α) ↑ fusion: (Mfn2) ↓ fission (DRP1)
de Carvalho 2021 [104]	C57BL/6 mice Sepsis	MSC cells Not specified	Dose: from 3*106 cells Administration: IV Site: jugular	↑ survival rate at day 2 (57 % vs. 36 %) ↓ bacteria load ↓ inflammation (IL1β), ↑IL10	Vascular endothelial cells: ↑basal & max respiration, Iuncoupled respiration Alveolar epithelial cells: ↑ max respiration, no effect on basal and uncoupled respiration
Hwang 2021 [105]	Sprague Dawley rat Sepsis	UC-MSC cells Rat Allogenic	Dose: 50 μg mito proteins Administration: IV Site: tail	↑ survival rate at day 14 (50 % vs. 10 %) ↑ bacterial clearance and ↓ lactate	↑ ATP level ↓ anti-ox (SOD2) ↑ ROS (DCFHDA) Restore O2 consumption spleen, muscle, no effect on liver, kidney, heart
Zhang 2021 [106]	C57BL/6 mice Sepsis	Pectoralis major Mice Allogenic	Dose: 2.5–3*107 mito Administration: IV Site: tail	↑ survival rate at day 7 (75 % vs. 36.8 %) ↑ bacterial clearance, nitrate + nitrite ↓ organ injury ↓ inflammation (IL1β and IL6) ↓ apoptosis	↓ OCR lung, liver, kidney, no effect on brain
Yan 2020 [107]	C57BL/6 mice Sepsis	Pectoralis major Mice Allogenic	Dose: 4*106 mito Administration: intraventricular Site: cerebral	No effect on mortality, mortice and explorative function ↑ memory retention performance ↑ cognitive impairment ↓ inflammation (TNFα, IL6, IL1β, TGFβ, IL4), no effect on IL10 ↓ apoptosis	↓ oxidative stress (iNOS)

ALAT: alanine aminotransferase, ATP: adenosine tri-phosphate, Cbln-2: cerebellin 2, DCFHDA: 2′,7′-dichlorodihydrofluorescein diacetate, DRP1: dynamin-related protein 1, IL: interleukin, iNOS: inducible nitric oxide synthase, IV: intra-veinous, LDH: lactate dehydrogenase, Mfn: mitofusin, mito: mitochondria, MSC: mesenchymal stromal cell, OCR: oxygen consumption rate, PGC1-α: Pparg coactivator 1-alpha, ROS: relative oxygen species, RT1-m2: major histocompatibility complex gene, SOD: superoxide dismutase, SIRT1: sirtuine 1, TGFβ: transforming growth factor beta, TNFα: tumor necrosis factor α, UC-MSC: Umbilical-cord MSC, ↑: increase/ improve, ↓: decrease.