Table 1.

Therapeutical applications of transplantation of MSCs-derived mitochondria and non-MSCs-derived mitochondria in various conditions

	Source	Target cells	Target disease	Effects	References
Coculture	iPSC-MSCs	Epithelial cells	Asthma inflammation	Alleviates asthma inflammation Decreases T helper 2 cytokine Decreases mitochondrial dysfunction of epithelial cells	[208]
	BM-MMSCs	Somatic cells with non-functional mitochondria	Tissue repair	Decreases production of extracellular lactate Decreases level of ROS Increases intracellular ATP Increases membrane potential Increases oxygen consumption	[35]
	UC-MSCs	T cells	Immune disease	Regulates autophagy Inhibits respiratory mitochondrial biogenesis Decreases T cell apoptosis	[72]
	iPSC-MSCs	Airway epithelial cells	Obstructive pulmonary disease	Rejuvenates damaged lung cells Increases alveolar surfactant Increases intracellular ATP	[24]
	hMMSCs	Renal tubular cells	Acute renal failure	Restores renal function status Increases intracellular ATP Increases oxygen consumption	[170, 209]
	BMSCs	Alveolar macrophage, alveolar epithelium	Acute respiratory distress syndrome	Increases alveolar macrophage phagocytosis Increases antimicrobial mechanism Decreases production of inflammatory factor Increases production of ATP Decreases severity of alveolar destruction and fibrosis	[18, 25]
	iPSC-MSCs BM-MSCs	Cigarette smoke-exposed airway epithelial cells	Chronic obstructive pulmonary disease	Decreases alveolar destruction Increases intracellular ATP	[167]
	iPSC-MSCs BM-MSCs	Cardiomyocytes Cardiomyoblasts	Ischemia/reperfusion Vascular disease	Prevents late cell death Increases mitochondria potential Increases gene expression in early cardiac commitment through partial cell fusion Recovers aerobic respiration Increases resistance against the ischemia/reperfusion apoptotic system Rescues aerobic respiration Protection from apoptosis Increases mitochondrial membrane potential	[172, 174, 175]
	hMMSCs	Astrocyte	Ischemia	Restores bioenergetics profile of recipient cells Stimulates proliferation	[178]
	hMMSCs	Cortical neurons	Stroke	Mitigates the pathological symptoms Restauration of neurological activity Reduction of brain lesion volume Alleviates inflammatory response Reduces apoptosis Rescues injured cells	[177]
	MSCs	Islets β-cells	Diabetes	Improves islet secretory functions Increases intracellular ATP	[169]
	hMMSCs	Renal proximal tubular epithelial cells	Diabetic nephropathy/diabetes	Suppresses apoptosis of damaged cells Inhibits ROS production Enhances the expression of mitochondrial superoxide dismutase 2 and Bcl-2 expression	[170]
	hMMSCs	Rat renal tubular cells	Diabetic nephropathy	Promotes differentiation into kidney tubular cells	[141]
	MSC/ECs	Cancer cells	Cancer	Promotes chemoresistance Decrease ROS production Contributes to proliferation and migration of cancer cells Increases intracellular ATP Favors the synthesis of metabolic intermediates to support the production of new biomass/cancer cells	[184, 189, 190, 193]
	iPSC-MSCs	Corneal damage and vision impairment	Corneal epithelial cells	Wound healing Protection against oxidative-stress-induced mitochondrial damage Protection against cell death and proliferation-inhibition	[180]
Injected mitochondria	Non-MSCs-derived mitochondria*	Nonischemic region mitigated myocardial injury	Liver ischemia/reperfusion injury	Significantly reduces I/R injury in the liver Supplements a working ROS scavenging system Increases ATP	[210]
		Tissue unaffected/myocardium	Ischemia/reperfusion Cold ischemia time (CIT)	Enhances myocardial function and cell viability Enhances post-ischemic functional recovery Decreases liver tissue injury and apoptosis Enhances graft function and Decreases graft tissue injury Increases in coronary blood flow	[211, 212]
		Human osteosarcoma cybrids	Parkinson’s disease	Increases mitochondrial function resulting in a resistance to neurotoxin-induced oxidative stress and apoptotic death Increases capacity for neurite outgrowth Improves locomotive activity in rats Decreases dopaminergic neuron loss	[213]
		Parent cybrid cells	Mitochondrial DNA mutation (myoclonic epilepsy with ragged-red fibers (MERRF) syndrome)	Mitochondrial function recovery and cell survival by preventing mitochondria-dependent cell death Increases mitochondrial biogenesis	[214]
		Nonischemic skeletal muscle	Dysfunction after ischemia–reperfusion injury Acute limb ischemia	Restores mitochondrial function and viability Improves post-ischemic myocardial function Ameliorates skeletal muscle injury Enhances hindlimb function in the murine model	[166]
		Brain macrophages, endothelium, pericytes, glia	Spinal cord injury: L1/L2 contusion	Microinjection into the spinal cord significantly restores respiration No differences in locomotion or kinematic stepping patterns	[215]
		Multiple tissues	Non-alcoholic fatty liver disease	Intravenously injected of mitochondria decreases serum aminotransferase activity and cholesterol level in a dose-dependent manner Reduces lipid accumulation and oxidation injury of the fatty liver mice Improves energy production Restores hepatocyte function	[216]
		Multiple tissues	Acetaminophen-induced liver injury	Intravenously injection of mitochondria increases hepatocyte energy supply Reduces oxidation stress Ameliorates tissue injury	[217]
		Renal tubular epithelium of the cortex and medulla	Acute kidney injury	Intra-arterial injection of mitochondria increases glomerular filtration rate and urine output Decreases serum creatinine and blood urea nitrogen Transplanted kidney shows patchy mild acute tubular injury	[218]
		Peri-infarct cortex	Transient focal cerebral ischemia	Upregulation of cell-survival-related signals in MCAO mice	[154]
	MSCs-derived mitochondria	Macrophages	ARDS	Lung macrophages that acquire MSC mitochondria increase phagocytic activity and anti-inflammatory phenotype	[18, 25]
		Alveolar epithelia	Acute lung injury	Intranasal instillation of mBMSCs increased alveolar ATP Abrogates alveolar leukocytosis and protein leak inhibits surfactant secretion Decreases high mortality	[24]
		Macrophages and several brain regions	Chemotherapy-induced cognitive deficits	Two nasal administrations of mitochondria restored the impaired working and spatial memory chemotherapy-induced	[219]

*The non-MSCs-derived mitochondria were isolated from different cell types, and the benefits effects of the therapy were annotated