Table 2.

Preclinical studies describing implication of MSCs and MSC-EVs mitochondrial transfer and MQC in renal and brain injury.

Organ	Preclinical Model	Treatment	Outcome	Mechanism	References
Kidney	Mouse renal IRI Tubular cell H/R	MSC-EVs	↓ Renal injury Renal function improvement	EV delivered miR-223-3p ↓ Inflammasome activation ↑ Mitophagy	Sun et al., 2022 [205]
	Mouse AKI Injured tubular cells	MSC-EVs	↓ Renal lesion formation ↓ Inflammation	↑ Mt energy production ↓ MtDNA damage and/or deletion TFAM pathway	Zhao et al., 2021 [161]
	Mouse AKI	UC-MSCs	↑ Renal repair ↓ Tubular damage	↑ Mt energy production ↑ Mt biogeneses ↑ PGC1α, NAD+, SIRT3	Perico et al., 2017 [206]
	Mouse renal IRI	MSC-EVs (tracked)	↓ Oxidative kidney damage ↑ Kidney function	↑ MtDNA copy number ↑ Mt ΔΨm stabilization and energy production Keap1-Nrf2 pathway	Cao et al., 2020 [8]
	Rat CKD	MSCs	Preserved residual renal function ↓ Kidney fibrosis	↓ Cell-stress signalling pathways (PI3K/Akt, pERK1/2, p-PKC and others)	Sheu et al., 2020 [207]
Brain and Neurons	MSC and injured PC-12 cells In vitro	Co-culture	↓ Apoptosis ΔΨm restoration	Mt transfer from MSCs to PC-12 by TNT formation	Yang et al. 2020 [214]
	Rat TBI and n vitro	Ad-MSCs and MSC-derived exosomes	Improved functional recovery	↓ Neuroinflammation ↑ Microglia/Mϕ shift to M2-like phenotype	Chen et al., 2020 [216]
	Rat TBI	Mt isolated from UC-MSCs	Improved motor function	↑ Neuronal formation and reparation ↓ Astrogliosis ↓ Microglial activation	Bamshad et al., 2023 [217]
	Rat contusion SCI	BM-MSCs	↑ Remyelination and functional recovery of motor neurons in SCI rats.	Mt transfer from BM-MSCs to injured motor neurons by the gap junctions	Li et al., 2019 [219]
	Cortical neuronal cells exposed to oxidant injury and MSCs n vitro	Co-culture	↑ Neuronal survival ↓ Oxidative injury	MSCs Mt transfer to damaged neuronal cells Role of Miro1 and TNT formation	Tseng et al., 2021 [157]
	Oxidative damage of hippocampal neurons (in vitro) and seizure mouse model	MSC-EVs (containing Mt)	↓ Hippocampal neuronal damage ↓ Sequelae of seizures in mice	↑ Antioxidant activity Nrf2 signaling pathway restoration ↓ ROS ↓ Mt dysfunction	Luo et al., 2021 [220]
	Rat TBI	MSCs or MSC- IL-10	MSCs-IL-10 > neuroprotection than MSCs alone	↑ Autophagy/mitophagy (NIX/BNIP3L), PINK-1 ↑ Cell survival ↓ Cell death ↓ Neuroinflammation	Maiti et al., 2019 [223]
	AD (ocadaic acid treated SH-SY5Y neuronal cells) n vitro	UC-MSC-CM	Cell protection Improved Mt function	EV and Mt transfer ↓ Expression of AD-related gene ↓ Mt oxidative stress	Zhang et al., 2020 [225]
	AD mouse model (repeated LPS-injections)	Regular and IL-6 primed MCSs	↓ episodic memory impairment Micro- and Microglial stimulation by primed MSCs	Improved Mt function in damaged brain cells ↓ Oxidative damage	Lykhmus et al., 2019 [226]
	Mouse MS	MSCs	↑ Myelinated areas	↑ Mt biogenesis ↑ Antioxidant levels	Shiri et al., 2021 [227]

Legend: ↑ increase; ↓ decrease; > greater.