Pathologies where mitochondrial transfer (or its blockage) has therapeutic impact
| Pathology . | Experimental model . | Route of administration* . | Result . | Reference . |
|---|---|---|---|---|
| Heart | ||||
| Ischemia | Heart regional ischemia | Injection into ischemic region | Enhanced myocardial functional recovery and cell viability | McCully et al., 2009 |
| Heart regional ischemia | Injection into ischemic region | Enhancement of post-ischemic myocardial function | Masuzawa et al., 2013 | |
| Heart global ischemia | Coronary artery injection | Enhancement of post-ischemic myocardial function | Cowan et al., 2016 | |
| Heart regional ischemia | Injection into ischemic region | Enhancement of myocardial cell viability | Kaza et al., 2017 | |
| Heterotopic heart transplantation | Coronary artery injection | Enhancement of graft function and attenuation of necrosis | Moskowitzova et al., 2019 | |
| Warm global ischemia | Coronary artery injection | Enhancement of post-ischemic myocardial function | Doulamis et al., 2020 | |
| Heart regional ischemia | Pre-ischemic coronary artery injection | Enhancement of post-ischemic myocardial function | Guariento et al., 2020 | |
| Liver | ||||
| Ischemia | Partial liver ischemia | Intrasplenic injection | Attenuation of hepatic injury | Lin et al., 2013 |
| Non-alcoholic fatty liver disease | Intravenous tail injection | Attenuation of lipid accumulation and oxidative stress | Fu et al., 2017 | |
| Acetaminophen-induced liver injury | Intravenous tail injection | Attenuation of tissue injury and enhancement of hepatocyte metabolism | Shi et al., 2018 | |
| Lungs | ||||
| Experimental lung silicosis | Intravenous injection of MSCs or MSC-derived exosomes | Reduction in the size of silicotic nodules, total number of white blood cells in BALF, and expression of inflammatory and pro-fibrotic genes in the lung | Phinney et al., 2015 | |
| Acute lung ischemia-reperfusion | Pulmonary artery injection and nebulization | Improvement of lung mechanics and attenuation of tissue injury | Moskowitzova et al., 2020 | |
| Pulmonary fibrosis | Intravenous tail injection of MSCs | Mitigation of fibrotic progression | Huang et al., 2021 | |
| Kidney | ||||
| Renal artery stenosis | Intra-arterially injection | Improved perfusion and oxygenation, protective effects on injured tubular cells | Zou et al., 2018 | |
| Diabetic nephropathy | Streptozotocin-induced diabetic rats | Injection under renal capsule | Improved cellular morphology and structure of the tubular basement membrane and brush border | Konari et al., 2019 |
| CNS | ||||
| Stroke | Middle cerebral artery occlusion | Intravenous injection | Decrease of brain infarction area and partial neurological status restoration | Babenko et al., 2015 |
| Middle cerebral artery occlusion | Injection into ischemic striatum | Attenuation of brain infarction area and neuronal death, restoration of motor performance | Huang et al., 2016 | |
| Middle cerebral artery occlusion | Intravenous injection | Restoration of neural function | Babenko et al., 2018 | |
| Middle cerebral artery occlusion | Intra-arterial injection of MSCs | Improved mitochondrial function in peri-infarct area and functional recovery | Wang et al., 2019 | |
| Middle cerebral artery occlusion | Intracerebro-ventricular injection | Promotion of neuroprotection, reduced brain infarct size, induced neurogenesis | Zhang et al., 2019 | |
| PD | Neurotoxin 6-hydroxydopamine induced PD | Medial forebrain bundle injection | Attenuation of oxidative damage and degeneration of dopaminergic neurons, and improved locomotion | Chang et al., 2016 |
| Neurotoxin MPTP induced PD | Intravenous injection | Reduction of neuronal death and attenuation of damage by ROS and improved behavioral symptoms | Shi et al., 2018 | |
| Schizophrenia | Poly-I:C induced schizophrenia | Prefrontal cortex injection | Prevention of the loss of brain ∆ψm and attention deficit in adulthood | Robicsek et al., 2018 |
| AD | AD model produced by the intra-cerebro-ventricular injection of Aβ peptide | Intravenous injection (tail) | Attenuation of neuronal loss and reactive gliosis, restoration of cognitive deficits | Nitzan et al., 2019 |
| Depression | LPS-induced model of depression | Intravenous injection | Improved symptoms such as exploratory behavior and promotion of neurogenesis, antidepressant-like effects | Wang et al., 2019 |
| Aging | Aged mice (18 mo) | Intravenous injection (tail) | Significant improvement of cognitive and motor performance of aged mice | Liu et al., 2019 |
| Spinal cord | Spinal cord injury | Mediolateral gray matter of injury site | Maintenance of acute bioenergetics, functional recovery | Zhao et al., 2020 |
| Spinal cord ischemia | Intravenous injection (jugular) | Improved hindlimb motor function | Feng et al., 2019; Gollihue et al., 2018 | |
| Spinal cord injury | Injected into the epicenter of the injured spinal cord | Improved locomotor functional recovery | Li et al., 2019 | |
| Glaucoma | Optic nerve crush | Intravitreal injection | Promoted short-term neuroprotection (14 d) to retinal ganglion cells and modulated retinal oxidative metabolism; importantly, mitochondria also increased the number of axons extending ahead of the injury site in a long-term period (28 d) | McCully et al., 2017 |
| Retinal ganglion cell degeneration | Ndufs4 knockout mouse model | Vitreous cavity injection | Protection against mitochondrial damage-induced retinal ganglion cell loss | Jiang et al., 2019 |
| Corneal injury | Alkaline burn-induced corneal damage | Transplantation of MSC scaffold to the center of the cornea | Improved corneal wound healing | Jiang et al., 2016 |
| Cancer | ||||
| Melanoma lung metastasis | Intravenous tail injection | Retardation of tumor growth and prolonged animal survival | Fu et al., 2019 | |
| MM | Intravenous injection of CD38 myeloma cells | Targeting of CD38 reduced significantly mitochondrial transfer and improved animal survival | Marlein et al., 2019 | |
| Glioma cell (U87) xenograft tumors | Injection into xenograft | Inhibited glioma growth, enhanced radiosensitivity of gliomas | Sun et al., 2019 | |
| Embryonic development | In vitro blastocyst stage development | Injection into zygotes | Improved embryonic development | Yi et al., 2007 |
| Tissue injury | Full-thickness cutaneous wound and dystrophic skeletal muscle | Engraftment of MSCs and platelets into the wound area | Enhanced therapeutic efficacy of MSCs | Levoux et al., 2021 |
| BM transplantation (BMT) | Total body irradiation as a preconditioning mechanism before BMT | Intravenous tail injection of BM cells | Rapid recovery of BM microenvironment, improved hematopoietic reconstitution after BMT | Golan et al., 2020 |
| Pathology . | Experimental model . | Route of administration* . | Result . | Reference . |
|---|---|---|---|---|
| Heart | ||||
| Ischemia | Heart regional ischemia | Injection into ischemic region | Enhanced myocardial functional recovery and cell viability | McCully et al., 2009 |
| Heart regional ischemia | Injection into ischemic region | Enhancement of post-ischemic myocardial function | Masuzawa et al., 2013 | |
| Heart global ischemia | Coronary artery injection | Enhancement of post-ischemic myocardial function | Cowan et al., 2016 | |
| Heart regional ischemia | Injection into ischemic region | Enhancement of myocardial cell viability | Kaza et al., 2017 | |
| Heterotopic heart transplantation | Coronary artery injection | Enhancement of graft function and attenuation of necrosis | Moskowitzova et al., 2019 | |
| Warm global ischemia | Coronary artery injection | Enhancement of post-ischemic myocardial function | Doulamis et al., 2020 | |
| Heart regional ischemia | Pre-ischemic coronary artery injection | Enhancement of post-ischemic myocardial function | Guariento et al., 2020 | |
| Liver | ||||
| Ischemia | Partial liver ischemia | Intrasplenic injection | Attenuation of hepatic injury | Lin et al., 2013 |
| Non-alcoholic fatty liver disease | Intravenous tail injection | Attenuation of lipid accumulation and oxidative stress | Fu et al., 2017 | |
| Acetaminophen-induced liver injury | Intravenous tail injection | Attenuation of tissue injury and enhancement of hepatocyte metabolism | Shi et al., 2018 | |
| Lungs | ||||
| Experimental lung silicosis | Intravenous injection of MSCs or MSC-derived exosomes | Reduction in the size of silicotic nodules, total number of white blood cells in BALF, and expression of inflammatory and pro-fibrotic genes in the lung | Phinney et al., 2015 | |
| Acute lung ischemia-reperfusion | Pulmonary artery injection and nebulization | Improvement of lung mechanics and attenuation of tissue injury | Moskowitzova et al., 2020 | |
| Pulmonary fibrosis | Intravenous tail injection of MSCs | Mitigation of fibrotic progression | Huang et al., 2021 | |
| Kidney | ||||
| Renal artery stenosis | Intra-arterially injection | Improved perfusion and oxygenation, protective effects on injured tubular cells | Zou et al., 2018 | |
| Diabetic nephropathy | Streptozotocin-induced diabetic rats | Injection under renal capsule | Improved cellular morphology and structure of the tubular basement membrane and brush border | Konari et al., 2019 |
| CNS | ||||
| Stroke | Middle cerebral artery occlusion | Intravenous injection | Decrease of brain infarction area and partial neurological status restoration | Babenko et al., 2015 |
| Middle cerebral artery occlusion | Injection into ischemic striatum | Attenuation of brain infarction area and neuronal death, restoration of motor performance | Huang et al., 2016 | |
| Middle cerebral artery occlusion | Intravenous injection | Restoration of neural function | Babenko et al., 2018 | |
| Middle cerebral artery occlusion | Intra-arterial injection of MSCs | Improved mitochondrial function in peri-infarct area and functional recovery | Wang et al., 2019 | |
| Middle cerebral artery occlusion | Intracerebro-ventricular injection | Promotion of neuroprotection, reduced brain infarct size, induced neurogenesis | Zhang et al., 2019 | |
| PD | Neurotoxin 6-hydroxydopamine induced PD | Medial forebrain bundle injection | Attenuation of oxidative damage and degeneration of dopaminergic neurons, and improved locomotion | Chang et al., 2016 |
| Neurotoxin MPTP induced PD | Intravenous injection | Reduction of neuronal death and attenuation of damage by ROS and improved behavioral symptoms | Shi et al., 2018 | |
| Schizophrenia | Poly-I:C induced schizophrenia | Prefrontal cortex injection | Prevention of the loss of brain ∆ψm and attention deficit in adulthood | Robicsek et al., 2018 |
| AD | AD model produced by the intra-cerebro-ventricular injection of Aβ peptide | Intravenous injection (tail) | Attenuation of neuronal loss and reactive gliosis, restoration of cognitive deficits | Nitzan et al., 2019 |
| Depression | LPS-induced model of depression | Intravenous injection | Improved symptoms such as exploratory behavior and promotion of neurogenesis, antidepressant-like effects | Wang et al., 2019 |
| Aging | Aged mice (18 mo) | Intravenous injection (tail) | Significant improvement of cognitive and motor performance of aged mice | Liu et al., 2019 |
| Spinal cord | Spinal cord injury | Mediolateral gray matter of injury site | Maintenance of acute bioenergetics, functional recovery | Zhao et al., 2020 |
| Spinal cord ischemia | Intravenous injection (jugular) | Improved hindlimb motor function | Feng et al., 2019; Gollihue et al., 2018 | |
| Spinal cord injury | Injected into the epicenter of the injured spinal cord | Improved locomotor functional recovery | Li et al., 2019 | |
| Glaucoma | Optic nerve crush | Intravitreal injection | Promoted short-term neuroprotection (14 d) to retinal ganglion cells and modulated retinal oxidative metabolism; importantly, mitochondria also increased the number of axons extending ahead of the injury site in a long-term period (28 d) | McCully et al., 2017 |
| Retinal ganglion cell degeneration | Ndufs4 knockout mouse model | Vitreous cavity injection | Protection against mitochondrial damage-induced retinal ganglion cell loss | Jiang et al., 2019 |
| Corneal injury | Alkaline burn-induced corneal damage | Transplantation of MSC scaffold to the center of the cornea | Improved corneal wound healing | Jiang et al., 2016 |
| Cancer | ||||
| Melanoma lung metastasis | Intravenous tail injection | Retardation of tumor growth and prolonged animal survival | Fu et al., 2019 | |
| MM | Intravenous injection of CD38 myeloma cells | Targeting of CD38 reduced significantly mitochondrial transfer and improved animal survival | Marlein et al., 2019 | |
| Glioma cell (U87) xenograft tumors | Injection into xenograft | Inhibited glioma growth, enhanced radiosensitivity of gliomas | Sun et al., 2019 | |
| Embryonic development | In vitro blastocyst stage development | Injection into zygotes | Improved embryonic development | Yi et al., 2007 |
| Tissue injury | Full-thickness cutaneous wound and dystrophic skeletal muscle | Engraftment of MSCs and platelets into the wound area | Enhanced therapeutic efficacy of MSCs | Levoux et al., 2021 |
| BM transplantation (BMT) | Total body irradiation as a preconditioning mechanism before BMT | Intravenous tail injection of BM cells | Rapid recovery of BM microenvironment, improved hematopoietic reconstitution after BMT | Golan et al., 2020 |
administration of mitochondria unless stated otherwise