Table 2.

Summary of intercellular mitochondrial transfer under pathological conditions

Donors	Recipients	Induction factor	Transferred cargoes	Route	Transfer outcomes	Ref.
CNS
Astrocytes	Neurons	Ischemic damage	Healthy mitochondria	MVs (CD38)	Restoration of ATP levels and neuronal viability	12
MMSCs	Neurons	Ischemic damage	Healthy mitochondria	TNTs	Recovery of respiration and neurological functions	31
MMSCs	Astrocytes	Ischemic damage	Healthy mitochondria	TNTs (Miro1)	Restoration of bioenergetics and promotion of cell proliferation	32
EPCs	Brain endothelial cells	OGD	Isolated mitochondria	Internalization	Elevated levels of mitochondrial protein, mtDNA copy number, and intracellular ATP; restoration of endothelial tightness	35
Astrocytes	Cerebrospinal fluid	Subarachnoid hemorrhage	Healthy mitochondria	Not verified	Brain recovery and good clinical outcomes	36
PC12 cells Soleus cells	Spinal cord-resident cells	SCI	Isolated mitochondria	Internalization	Maintenance of acute bioenergetics after SCI	37
BM-MSCs	Motor neurons	OGD/SCI	Healthy mitochondria/isolated mitochondria	TNTs/gap junction	Improved bioenergetics profile and cell survival in post-OGD motor neurons; locomotor functional recovery after SCI	38
MSCs	NSCs	Cisplatin	Healthy mitochondria	TNTs (Miro1)	Decrease of NSC death and restoration of mitochondrial membrane potential	39
Astrocytes	Neurons	Cisplatin	Healthy mitochondria	Not verified	Increased neuronal survival and restored neuronal calcium dynamics	40
HeLa cells	AD mice model	None	Isolated mitochondria	Intravenous injection	Amelioration of cognitive deficits, neuronal loss, and gliosis in Alzheimer’s disease mice	41
Astrocytes	Astrocytes	α-Syn ingestion and accumulation	Healthy mitochondria	TNTs	Potential rescue of mitochondrial dysfunction in stressed α-syn-containing astrocytes	43
Cardiovascular system
Pectoralis major muscle cells	CMs	Ischemic damage	Isolated mitochondria	Internalization	Decreased heart infarct size of rabbits	56
BM-MSCs	Cardiomyoblasts	Ischemic damage	Healthy mitochondria	TNTs	Rescue of cardioblasts from cell death	57
MFs	CMs	Hypoxia/reoxygenation damage	Healthy mitochondria	TNTs	Rescue of CMs from apoptosis	58
MSCs	CMs	LPS-induced stress	Healthy mitochondria	TNTs	Enhancement of cardiomyocyte function	59
iPSC-MSCs	CMs	Anthracycline-induced cardiomyopathy	Healthy mitochondria	TNTs (TNFαip2, Miro1)	Rescue of CMs damage	60
Respiratory system
BMSCs	Alveolar epithelium cells	LPS-induced ALI	Healthy mitochondria	TNTs/MVs (Cx43)	Restoration of alveolar bioenergetics and elevation of the survival rate	11
iPSC-MSCs	Bronchial epithelial cells (BEAS-2B)	CS-induced COPD	Healthy mitochondria	TNTs	Alleviation of CS-induced ATP depletion and lung damage	61
MSCs	Lung epithelial cells	Rotenone-induced airway injury	Healthy mitochondria	TNTs (Miro1)	Decrease in apoptosis and lung injury repair	69
iPSC-MSCs	Bronchial epithelial cells (BEAS-2B)	Ovalbumin- or CoCl2-induced mitochondrial dysfunction	Healthy mitochondria	TNTs (Cx43)	Alleviation of airway inflammation and cell apoptosis	64
Musculoskeletal system
BM-MSCs	Chondrocytes	Rotenone and oligomycin	Healthy mitochondria	Not verified	Not verified	71
Osteocytes/MLO-Y4 cell lines	MLO-Y4 ρ° cells	EB-induced mtDNA deletion	Healthy mitochondria	Cell dendrites (ER–mitochondria contact)	ATP reproduction and alleviation of oxidative stress	73
Other systems
BM-MSCs	HUVECs	OGD and reoxygenation	Healthy mitochondria	TNTs	Aerobic respiration and protection of endothelial cells from apoptosis	74
Healthy or MCA-treated human MSCs	Injured human MSCs	H2O2-induced oxidative stress	Healthy mitochondria	TNTs	Decrease of oxidative stress and increase of human MSC viability	76
iPSC-MSCs	Corneal epithelial cells	Rotenone-induced mitochondrial dysfunction	Healthy mitochondria	TNTs (TNFαip2)	Protection against oxidative stress and repair of cornea	75
WJ-MSCs	MERRF cybrid cells	mtDNA mutation	Healthy mitochondria	TNTs	Reduction of ROS and improvement of mitochondrial bioenergetics	78
Tumorigenesis and tumor therapy resistance
MSC skin fibroblasts	Lung adenocarcinoma A549 ρ° cells	EB-induced mtDNA deletion	Healthy mitochondria/mtDNA	Cytoplasmic extensions or broad cellular contact	Recovery of respiratory function and oxidative metabolism	10
Cells in TME of the host mouse	Breast carcinoma 4T1 ρ° cells	EB-induced mtDNA deletion	mtDNA	Not verified	Recovery of respiratory capacity and tumor growth	94
MSCs	Melanoma B16 ρ° cells	EB-induced mtDNA deletion	Healthy mitochondria	Not verified	Recovery of respiratory capacity and tumor growth	95
hMSCs	Breast cancer MDA-MB-231 cells	None	Isolated mitochondria	Internalization	Increased proliferation and invasion capacities of cancer cells	93
BM-MSCs	Osteosarcoma 143B ρ° cells	EB or rhodamine 6G-induced mitochondrial dysfunction	Healthy mitochondria	Not verified	Increase of intracellular ATP levels and restoration of mitochondrial function	15
WJ-MSCs	Osteosarcoma 143B ρ° cells	EB-induced mtDNA deletion	Healthy mitochondria	TNTs	Restoration of bioenergetics and OXPHOS-dependent cellular growth	77
Mesothelioma cells	Mesothelioma cells	Acidified hyperglycemic medium	Vesicles, mitochondria, proteins—bidirectional	TNTs	Cancer cell pathogenesis and invasion	83
T24 bladder cancer cells	RT4 bladder cancer cells—noninvasive	None	Healthy mitochondria	TNTs	Increased invasiveness of RT4 cells	98
BMSCs	Primary AML blasts	None	Healthy mitochondria	TNTs (NOX2, ROS)	Energy acquirements of the proliferating cancer cells	89
	Nonmalignant CD34+ cells	H2O2		Not verified	Not clarified
Highly glycolytic CAFs	Prostate cancer cells	None	Healthy mitochondria	TNTs	Increased OXPHOS metabolism and respiratory capacity of cancer cells	97
Neighboring nonmalignant BMSCs	Multiple myeloma cells	None	Healthy mitochondria	TNTs (CD38, direct contact)	Increased ATP production and mitochondrial respiration of multiple myeloma cells	84
Endothelial cells, MSCs	MCF7 breast cancer cells	Doxorubicin	Healthy mitochondria	TNTs	Chemoresistance	92
Healthy PC12 cells	Pheochromocytoma-derived PC12 cells	UV radiation	Healthy mitochondria	TNTs	Rescue of apoptotic P12 cells	87
Astrocytoma cells	Astrocytoma cells	Radiation treatment	Mitochondria, Calcium	Tumor microtubules (Cx43)	Formation of a self-repairing and radio-resistant network	85
U87 glioblastoma cells	Adjacent U87 glioblastoma cells	Etoposide	Mitochondria	TNTs	Perinuclear concentration and rearrangement of mitochondria	86
Bone marrow-derived MS-5 cell line	AML cells	Cytarabine	Healthy mitochondria	Endocytosis	Increase of ATP production and survival capacity of AML cells following chemotherapy	88
Chemoresistant ovarian cancer cells	Chemoresistant or chemosensitive ovarian cancer cells	Hypoxia	Mitochondria	TNTs (mTOR pathway)	Synchronization of cancer cells against drug therapy	96
Immunoregulation
BM-MSCs	Monocyte-derived macrophages	LPS-induced ARDS	Healthy mitochondria	TNTs	Enhance the phagocytic effect of macrophages	62
BM-MSCs	Monocyte-derived macrophages	Escherichia coli infection	Healthy mitochondria	TNTs	Enhance the oxidative phosphorylation and phagocytosis of macrophages	104
BM-MSCs	Macrophages	LPS-induced ARDS	Healthy mitochondria	MVs	Promote an anti-inflammatory and highly phagocytic phenotype of macrophagy and ameliorate lung injury	63
BM-MSCs	Th17 cells	IL-2	Healthy mitochondria	Cell contact-dependent manner	Increased oxygen consumption and reduced production of pro-inflammatary cytokines; generation of T-regulatory cells	105
MSCs	PBMCs	None	Healthy mitochondria	Not verified	T cell activation and T-regulatory (Treg) cell differentiation; suppressive effect of inflammatory response	106
	CD3+ T cells		Isolated mitochondria	Internalization
Intercellular degradation
Retinal ganglion cells	Adjacent astrocytes	Rotenone	Damaged mitochondria	MVs	Donors: mitophagy for transcellular degradation and self-protection	21
BM-MSCs	Macrophages	Oxidative stress to MSCs	Depolarized mitochondria	MVs	Donors: Mitophagy of MSCs for self-protection Recipients: enhancement of macrophage energetics	107
T-ALL cells	BM-MSCs	Ara-C- or MTX-induced intracellular oxidative stress	Damaged mitochondria	TNTs	Donors: mitophagy for reduction of intracellular ROS and enhancement of chemoresistant capacity	91
BM-MSCs	T-ALL cells	Ara-C- or MTX-induced intracellular oxidative stress	Healthy mitochondria	TNTs	Recipients: chemoresistance	91
Stressed CMs or HUVECs	MSCs	H2O2-induced oxidative stress	Damaged mitochondria	TNTs (ROS)	Donors: transmitophagy of stressed cells	113
MSCs	Stressed CMs or HUVECs	H2O2-induced oxidative stress	Healthy mitochondria	TNTs (HO-1)	Recipients: survival of stressed cells	113