Table 2.

Current application of mitochondrial and its component transplantation

Disease Model	Animal	Format	Mitochondrial Source	Methods	Effect	Ref
Ischemia/reperfusion (I/R)
Myocardial ischemia	NZW rabbitsa)	Mitochondria	Left ventricular	Local injection	↑: Postischemic recovery; ↓: Infarct size	47
Myocardial ischemia	NZW rabbits	Mitochondria	Pectoralis major muscle	Local injection	↑: Postinfarct cardiac function, angiogenesis, immunomodulation;	372
					↓: Myocardial necrosis, apoptosis, and infarction size
Hepatic ischemia	Wistar rats	Mitochondria	Rat liver	Splenic injection	↓: Tissue insults, oxidative stress, cell death	375
MCAOb)	Sprague–Dawley rat	Mitochondria	BHK-21 cell	IC & IA injectionc)	↑: Functional recovery of motor activities, neuron survival; ↓: Brain lesion	376
Stroke	C57BL/6 J mice	Mitochondria	Astrocyte	Direct injection	↑: Cell-survival-related signals, plasticity	43
MCAO	Sprague–Dawley rat	Mitochondria	Autologous muscle	ICVd) injection	↑: Neurogenesis; ↓: Brain infarct volume, oxidative stress, and cell death	448
Warm ischemia	Zucker diabetic fatty rat	Mitochondria	Skeletal muscle	ICAe) infusion	↑: Mitochondrial function; ↓: Infarct size, oedema	449
Heart transplantation	C57BL/6 J mice	Mitochondria	Gastrocnemius muscle	ICA infusion	↑: Cold ischemic time; ↓: Graft tissue injury, neutrophil infiltration	374
Myocardial ischemia	Yorkshire swine	Mitochondria	Pectoralis major muscle	ICA infusion	↑: Coronary blood flow, myocardial function, perfusion; ↓: Infarct size	450
Acute limb ischemia	C57BL/6 J mice	Mitochondria	muscle	Direct injection	↑: Hindlimb function, inflammation; ↓: Infarct size, apoptosis	377
Myocardial ischemia	CD1 mice	EVs	iCMs	Direct injection	↑: Mitochondrial biogenesis; ↓: Cardiac remodeling	390
Renal I/R injury	C57BL/6 mice	mtDNA, TFAM mRNA, proteins	Mouse MSC	IVf) injection	↓: Renal lesion, inflammation	451
Hepatic ischemia	C57BL/6 mice	Mitochondria	hUC-MSC-EVs	IV injection	↓: Hepatocyte apoptosis, proinflammatory cytokines, NETg) formation	452
Neurodegenerative disorders and aging
Parkinson’s disease	Sprague–Dawley rat	Mitochondria, P-mitoh)	PC12, human osteosarcoma	Local injection	↓: Deterioration of dopaminergic neurons, movement disorders	379
Parkinson’s disease	C57BL/6 J mice	Mitochondria	HepG2 cell	IV injection	↑: Behavioral symptoms, biochemical assay results	380
Parkinson’s disease	Sprague–Dawley rat	Mitochondria, P-mito	Allogeneic liver	INi) infusion	↑: Rotational and locomotor behavior; ↓: Mitochondrial oxidative damage	393
Alzheimer’s disease	C57BL/6 mice	Mitochondria	HeLa cell	ICV injection	↑: Cognitive performance; ↓: Gliosis, neuron loss	394
Alzheimer’s disease	NMRI mice	Mitochondria	Allogeneic brain	IN infusion	↑: Spatial memory with Alzheimer’s type degeneration	395
Aging	BABL/c mice	Mitochondria	Mice liver	IV injection	↑: Learning and memory ability, muscle function, immune responses	396
Aging	Wistar rats	Mitochondria	Rat brain	ICV injection	↑: Mitochondrial function; ↓: Depression like behaviors	397
Psychiatric disorders
MDDj)	ICR mice	Mitochondria	Hippocampus	IV injection	↑: Antidepressant-like activity; ↓: Neuroinflammation	381
Cognitive deficits	C57BL/6 J mice	Mitochondria	Human MSC	IN infusion	↓: White matter and synaptic loss, synaptosomal mitochondrial deficiencies	400
Hepatic non-ischemic disorders
NAFLD	C57BL/6 J mice	Mitochondria	HepG2 cells	IV injection	↑: Redox balance; ↓: Lipid content	405
Liver injury	C57BL/6 J mice	Mitochondria	HepG2 cells	IV injection	↑: Hepatic function; ↓: Decreased hepatotoxicity	408
NASH	C57BL/6 J mice	microRNA	Human liver	IV injection	↓: High Fat Diet-Induced Cirrhosis, insulin resistance, fibrosis	429
Liver injury	Kunming mice	Mitochondria	Allogeneic liver	IV injection	↑: Stress resistance, proteostasis; ↓: Oxidation, fibrosis	407
Lung non-ischemic disorders
Acute lung injury	C57BL/6 J mice	MSC	Mouse BMSCs	IN infusion	↑: Mouse survival time; ↓: Leukocytosis, albumin leakage	413
ARDS	Sprague–Dawley rat	Melatonin–mitochondria	Allogeneic liver	IV injection	↑: Respiratory and circulatory functions; ↓: Oxidative stress, apoptosis	385
Silicosis	C57BL/6 J mice	microRNA	Human MSC	IV injection	↑: Bioenergetics; ↓: Monocyte infiltration, inflammation, fibrosis	41
COPD	Sprague–Dawley rat	Mitochondria	Airway epithelium	ITk) instillation	↓: Airway hyperresponsiveness to acetylcholine, inflammation	416
ARDS	C57BL/6 mice	Mitochondria	Human MSC	IN infusion	↑: Microbial clearance, phagocytosis of alveolar macrophages	417
Acute lung injury	C57BL/6 mice	EVs	Human MSC	IN infusion	↓: Inflammatory cell recruitment, lung injury	418
Asthma	BALB/c mice	Mitochondria	iPSC-MSCl)	IT instillation	↑: Mitochondrial function; ↓: Asthma inflammation	415
Acute lung injury	C57BL/6 mice	mtDNA and proteins	Human adipose MSC	IV injection	↑: Macrophage mitochondrial function; ↓: Lung inflammation and injury	384
Central nerve injuries
Spinal cord injury	Sprague–Dawley rat	Mitochondria	BHK Cells	Local injection	↑: Rat neurobehaviors, nerve electrophysiology, muscle activities;	420
					↓: Oxidative stress and the secondary inflammatory response
Spinal cord injury	Sprague–Dawley rat	Mitochondria	bilateral soleus muscles	Local injection	↑: Sensory and locomotor functions;	421
					↓: Demyelination, oxidative stress, mitochondrial fragmentation, apoptosis
Spinal cord injury	Sprague–Dawley rat	Mitochondria	Rat BMSCs	Direct injection	↑: Locomotor function recovery	422
Spinal cord injury	C57BL/6 mice	P-mito	BMDMsm)	IV injection	↑: Lower limb motor function, nerve innervation, macrophage repair;	423
					↓: mitochondrial dysfunction and proinflammatory profile of macrophage
Other diseases
Multiple sclerosis	C57BL/6 mice	EVs	Neuro stem cell	ICV injection	↓: Auxotrophy, neuroinflammation	425
Tendinopathy	Sprague–Dawley rat	Mitochondria	L6 rat myoblast cell	Local injection	↓: Inflammation, apoptosis	426
Wound and muscle dystrophy	C57BL/6, sgcanull mice	Mitochondria	Human platelet	Direct injection	↑: Pro-angiogenic function, myogenesis	424
Osteoarthritis	Male Wistar rats	Mitochondria	L6 rat myoblast cell	Direct injection	↑: Bone surface, bone volume; ↓: Joint destruction, autophagy	427

^a)NZW New Zealand White

^b)MCAO middle cerebral artery occlusion

^c)IA intra-artery; IC Intracerebral

^d)ICV intracerebroventricular

^e)ICA intracoronary artery

^f)IV intravenous

^g)NET neutrophil extracellular traps

^h)P-mito Peptide-mediated mitochondria

ⁱ⁾IN intranasal

^j)MDD Major depressive disorder

^k)IT intratracheal instillation

^l)iPSCs induced-pluripotent stem cells

^m)BMDMs bone marrow-derived macrophages