Table 1 Transfer of mitochondrial donation in different in vivo and in vitro systems
From: Mitochondrial donation in translational medicine; from imagination to reality
Milieu | Donor cells | Recipient cells | Outcome | References |
|---|---|---|---|---|
In vitro | Human bone marrow MSCs | Adult mouse cardiomyocytes | Mitochondrial transfer is required for somatic cell reprogramming | [129] |
Heterologous cell fusion promoted cardiomyocyte reprogramming back to a progenitor-like state. | ||||
In vivo | Human induced-pluripotent-stem-cell-derived MSCs (iPSC-MSCs) | Cardiomyocytes | iPSC-MSCs has superior effect to transfer mitochondria due to enhanced expression of Miro-1 | [72] |
The higher levels of TNFαIP2 expression in iPSC-MSCs make them respond to TNF-α-induced TNT formation to transfer mitochondria to anthracycline-induced cardiomyocytes. | ||||
Suppression of TNFαIP2 or MIRO1 in iPSC-MSCs aborted mitochondrial transfer. | ||||
In vitro | Human MSCs | Rat cardiomyocytes | The co-culture of rat cardiomyocytes with human MSCs increased the number of TNTs. | [142] |
In vitro and in vivo | Rabbit fibroblast isolated from cardiac tissue | Adult rabbits cardiomyocytes | An inter-cytoplasmic connection is provided between fibroblasts and dedifferentiated cardiomyocytes. | [143] |
Disruption of the basal lamina was initiated after TNT formation in the border zone of a rabbit myocardial infarction. | ||||
In vitro | Normal mouse MSCs | Ischemic H9C2 cardiomyoblasts | Wide (200–500 nm) intercellular connections formed between the rat cardiomyoblasts and mouse MSCs | [93] |
Cell fusion rarely occurred between the rat cardiomyoblasts and mouse MSCs. | ||||
In vitro | Rat MSCs | Rat neonatal cardiomyocytes | MSCs make cell-to-cell connection by initial extension of filopodia. | [134] |
Unidirectional transfer of mitochondria occurred between MSCs and cardiomyocytes. | ||||
Compared to the MSCs, few TNT formations were observed between the cardiac fibroblasts and cardiomyocytes in a homotypic or mixed cell population. | ||||
In vivo | Mouse astrocytes | Mouse neurons | CD38 and cyclic ADP ribose signaling participate in mitochondrial transfer | [6] |
In vitro | Bone marrow MSCs | Rat renal tubular cells | The transport of cellular components was started three hours after co-culturing | [144] |
Both anterograde and retrograde mitochondrial transfer were seen between the MSCs and renal tubular cells. | ||||
Renal-specific Tamm-Horsfall protein was induced in MSCs after connection to the renal cells, promoting MSCs differentiation toward tubular cells. | ||||
In vitro | Adult human endothelial progenitor cells | Rat cardiomyocytes | The number endothelial progenitor cell-derived TNTs increased six hours after co-culturing. | [133] |
Transport of MitoTracker-positive structures was done from cardiomyocyte toward endothelial progenitor cells. | ||||
The acquisition of a cardiomyogenic phenotype was recorded in endothelial progenitor cells independent of cellular or nuclear fusion. | ||||
In vitro | Human bone marrow MSCs | Human umbilical vein endothelial cells (HUVECs) | TNT-like structure was performed between MSCs and HUVECs. | [47] |
Oxygen/glucose deprivation and re-oxygenation in HUVECs induced unidirectional mitochondrial transfer through TNTs from MSCs. | ||||
Formation of TNTs is a defense and rescue mechanism after exposure of phosphatidylserine on the surface of apoptotic endothelial cells. | ||||
In vitro and in vivo | Neonatal rat cardiomyocytes | Neonatal rat cardiomyocytes | Mitochondrial internalization is done through actin-dependent endocytosis. | [136] |
Internalized mitochondria replenished cardiomyocyte ATP content. | ||||
Oxygen consumption increased after mitochondrial internalization. | ||||
In vitro and in vivo | Cardiac fibroblasts | Myocytes | In response to cardiac injury, interactions between myofibroblasts and myocytes are enhanced, contributing to significant electrophysiological changes and influencing electrotonic connectivity between cardiomyocytes and fibroblasts and/or myofibroblasts | [145] |
In vitro | Human uterine endometrial gland MSCs | Rat H9C2 cardiomyoblasts | Mitochondrial transfer was seen in homogeneic and xenogeneic cells. | [140] |
Mitochondrial transfer rescued the mitochondrial respiratory function and improved the cellular viability in mitochondrial DNA-depleted cells. | ||||
Micropinocytosis participates in mitochondrial internalization. | ||||
In vitro | Rat MSCs | Neonatal cardiomyocytes | Connexin-43 was induced as junctional factors between the MSCs and cardiomyocytes. | [146] |
MSC-cardiomyocyte fusion was initiated. | ||||
Partial cell fusion and TNT accelerated the transfer of MSC mitochondria to the cardiomyocytes. | ||||
In vitro and in vivo | Rat cardiac fibroblasts | Neonatal rat cardiomyocytes | Microtubules and motor protein KIF5B are required for mitochondrial transport from fibroblasts to cardiomyocytes. | [147] |
The mitochondrial transfer was observed from fibroblast to hypoxia-treated cardiomyocytes but not vice versa | ||||
Intact and hypoxia/re-oxygenation-treated fibroblast decreased cardiomyocyte apoptosis by mitochondrial donation via TNTs. | ||||
In vitro and in vivo | Human-induced pluripotent stem cell (iPSC)-derived MSCs | Asthmatic epithelial cells | iPSC-MSC transplantation decreased T helper 2 related cytokines and blunted mitochondrial dysfunction in epithelial cells | [148] |
TNTs were formed between iPSC-MSCs and epithelial cells | ||||
Mitochondrial transfer was done from iPSC-MSCs to epithelial cells via TNTs | ||||
Connexin 43 plays a critical role in the regulation of TNT formation in iPSC-MSCs. |