Table 2 Summary of mitochondrial transfer/transplantation in different organ
From: Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases
Organ | Disease | Donor | Recipient | Methods | Therapeutic effect | Refs. |
|---|---|---|---|---|---|---|
Brain | Sepsis-associated brain dysfunction | Pectoralis (allogeneic) | Mouse left lateral ventricle/BV2 microglia | Mitochondrial transplantation (i.c.v. injection)/mitochondrial coincubation | Cognitive impairment↓ Microglial polarization from the M1 phenotype to the M2 phenotype | [193] |
Brain | Schizophrenia | Human lymphocytes/rat brain (xenogeneic) | Schizophrenia-derived lymphoblasts/rat prefrontal cortex neurons | Mitochondrial incubation/mitochondrial transplantation (DI) | Long-lasting cellular oxygen consumption and mitochondrial membrane potential↑ Attentional deficit↓ | [194] |
Brain | PD | HepG2 cells (xenogeneic) | Multiple tissues, including brain, liver, kidney, muscle, and heart tissues of mice | Mitochondrial transplantation (i.v. injection) | ETC activity↑ ROS level↓ Apoptosis and necrosis↓ | [195] |
Brain | PD | PC12 cells (allogeneic)/human osteosarcoma cybrids (xenogeneic) | PC12 cells/ rat dopaminergic neurons | Peptide-mediated mitochondrial incubation/peptide-mediated mitochondrial transplantation (i.c.v. injection) | Cell viability↑ Mitochondrial tolerance to 6-OHDA neurotoxicity↑ Motor function↑ Dopaminergic neuron deterioration↓ | [143] |
Brain | AD | HeLa cells (xenogeneic) | Brain and liver of mice | Mitochondrial transplantation (i.v. injection) | Cognitive performance↑ Neuronal loss↓ Gliosis↓ Mitochondrial dysfunction in brain↓ Mitochondrial activity in liver↑ | [142] |
Brain | IR injury | Pectoralis major (autologous) | Widespread distribution in the brain, mainly in ischaemic penumbra areas of the brains of rats | Mitochondrial transplantation (i.c.v. injection) | Cellular oxidative stress↓ Apoptosis↓ Astrogliosis↓ Neurogenesis↑ Brain infarct volume↓ Neurological deficits↓ | [196] |
Brain | IR injury | Rat MSCs (allogeneic) | Rat peri-infarct area of brain | MSC transplantation (intra-arterial injection) | Mitochondrial activity↑ Angiogenesis↑ Infarct volume↓ Functional recovery↑ | [197] |
Spine | Spinal cord injury | PC12 cells/soleus muscle (allogeneic) | Resident spinal cord cells of rats | Mitochondrial transplantation (DI) | Oxygen consumption rate↑ Long-lasting motor and sensory functions— | [198] |
Heart | Myocardial infarction | hMADS (xenogeneic) | hMADS/endothelial or cardiac cells/mouse myocardium | Coculture/hMADS transplantation (surrounding the infarcted site injection) | HO-1 expression↑PGC1 -α expression↑ Plasma cardiac troponin t levels↓ Intracardiac caspase-3 protein expression↓ | [93] |
Heart | Anthracycline-induced cardiomyopathy | Human iPSC-MSCs (xenogeneic) | NMCs | Coculture (TNTs)/iPSC-MSC transplantation (intramyocardial injection) | Mitochondrial respiration↑ NMC viability↑ | [106] |
Heart | Anthracycline-induced cardiomyopathy | Human iPSC-MSCs/BM-MSCs (xenogeneic) | Mouse myocardium | iPSC-MSC/BM-MSC transplantation (intramyocardial injection) | Heart function↑ Myocardial damage↓ Myocardial fibrosis↓ Cell apoptosis↓ ATP production↑ Oxidative stress↓ Inflammation↓ | [106] |
Heart | IR injury | Pectoralis major of rabbit (autologous) | Rabbit myocardium | Mitochondrial transplantation (DI) | Creatine kinase MB↓ Cardiac troponin-I↓ Apoptosis↓ Infarct size↓ Oxygen consumption↑ ATP production↑ Precursor metabolites for energy↑ Cellular respiration↑ | [74] |
Heart | IR injury | Human adult cardiac fibroblasts (xenogeneic)/ rabbit liver (autologous) | Rabbit myocardium | Mitochondrial transplantation (DI)/mitochondrial coronary vasculature perfusion | End diastolic pressure↓ Positive dp/dt↑ Segmental shortening↑ Infarct size↓ | [199] |
Lung | Acute respiratory distress syndrome | Human MSCs (allogeneic)/murine alveolar macrophages (allogeneic) | Human monocyte-derived macrophages/mouse LPS-injured lung | Noncontact coculture (EVs)/instillation of alveolar macrophages treated with MSC-derived EVs (intranasally instilled) | Macrophages OXPHOS↑ Anti-inflammatory response↑ Phagocytosis↑ Lung injury↓ | [132] |
Lung | Acute lung injury | Mouse BMSCs (allogeneic) | Mouse alveolar epithelium cells | BMSC transplantation (airway-instilled) | ATP concentrations↑ Alveolar leucocytosis↓ Protein leakage↓ Surfactant secretion↑ Mouse survival↑ | [30] |
Lung | Airway injury and allergic airway inflammation | MSCs (allogeneic) | Lung bronchial epithelial cells of mice | MSC transplantation (intratracheal or intranasal route) | Caspase-3↓ Caspase-9↓ Apoptosis↓ Inflammation↓ Mitochondrial function↑ | [114] |
Lung | Alveolar epithelial-capillary barrier disruption | MSCs (allogeneic) | Primary human pulmonary microvascular endothelial cells/human small airway epithelial cells/lung | EV cocultured/EV transplantation (i.v. injection) | Barrier integrity↑ Mitochondrial respiration ↑ ATP turnover↑ Mitophagy↓ mtDNA replication↑ Inflammatory response↓ Mitochondrial function↑ | [200] |
Liver | Carbon tetrachloride-induced liver injury | Mouse liver (allogeneic) | Mouse hepatocytes | Mitochondrial co‐incubation/mitochondrial transplantation (i.v. injection) | Liver injury↓ Liver fibrosis↓ ROS level↓ ATP content↑ OXPHOS↑ Cell proliferation↓ Xenobiotic metabolism transformation↑ Protein homeostasis↑ | [127] |
Kidney | Diabetic nephropathy | Rat BM-MSCs (allogeneic) | Rat renal proximal tubular epithelial cells/mouse kidney | Mitochondrial transplantation (under the renal capsule of rats)/MSC transplantation (i.v. injected)/coculture/mitochondrial coincubation | Colony formation↑ Apoptosis↓ SOD2↑ Bcl-2↑ ROS production↓ Megalin and SGLT2 expression↑ Renal tubules structural restoration↑ | [201] |
Bone | Bone defect | Rat BMSCs (autologous/allogeneic) | BMSCs/parietal bone of rats | Mitochondrial coincubation /mitochondria-recipient BMSC transplantation (DI) | Cell proliferation and migration↑ Osteogenic differentiation↑ Bone defect repair↑ OXPHOS↑ ATP production↑ | [148] |
Bone | Osteoarthritis | Rat BMSCs (allogeneic) | Rat chondrocytes | Coculture | Mitochondrial membrane potential↑ Mitochondrial respiratory chain enzymes activity↑ ATP content↑ Apoptosis↓ Type II collagen secretion↑ Proteoglycan protein↑ | [147] |
Skeletal muscle | Skeletal muscle atrophy | Human umbilical cord- MSCs (xenogeneic) | Rat myoblast cells | Centrifugation | Cell proliferation↑ ATP content↑ MMP↑ PGC-1↑ AMPK/FoxO3/Atrogene pathway↓ | [64] |
Skeletal muscle | Tendinopathy | Human umbilical cord-MSCs (allogeneic)/rat L6 myoblasts (allogeneic) | Human tenocytes/rat Achilles tendon | Centrifugation/Mitochondrial transplantation (DI) | Tenomodulin↑ Collagen 1↑ MMP1↓ ROS↓ ATP production↑ Mitochondrial fusion↑ Mitochondrial fission↓ Apoptosis↓ Inflammation↓ | [145] |